A NOVEL LOCAL THERAPY FOR BLADDER CANCER

 A novel intravesical gene therapy for bladder cancer has shown such promising results in clinical trials that experts are suggesting that it be considered the "new gold standard," even though it is not yet available.

The product, nadofaragene firadenovec, is being developed by FerGene Inc as a treatment for patients with high-grade bacillus Calmette-Guérin (BCG)–unresponsive non-muscle-invasive bladder cancer (NMIBC).

It is currently under consideration for approval by the US Food and Drug Administration.

The product is an adenovirus vector-based gene therapy containing the gene interferon alfa-2b. It is administered by catheter into the bladder once every 3 months. The vector enters the cells of the bladder wall, the gene turns on, and the cells then secrete high quantities of the interferon alfa-2b protein.

This approach "turns the patient's own bladder wall cells into interferon microfactories, enhancing the body's natural defenses against the cancer," the manufacturer explains.

New clinical results were published online November 27 in The Lancet Oncology.

At median follow-up of 19.7 months, a complete response (CR) was seen in about half of patients (53.4%, 55 of 103 patients) with BCG-unresponsive NMIBC in situ (with or without a high-grade Ta or T1 tumor), who received an initial dose of the investigational therapy in the single-arm, open-label, repeat-dose trial.

For 25 patients (45.5%), response was maintained at 12 months, report the investigators, led by Stephen A. Boorjian, MD, of the Mayo Clinic, Rochester, Minnesota.

These patients were among 151 treated in the trial between September 19, 2016, and May 24, 2019, and were included in a per-protocol efficacy analysis. All CRs occurred within 3 months of the initial treatment. The duration of CR was 9.69 months.

The remaining 48 patients had high-grade Ta or T1 disease. Of these patients, 35 were free of high-grade recurrence at month 3; 21 of these patients remained recurrence-free at month 12. Median follow-up in that cohort was 20.2 months, and median duration of high-grade recurrence-free survival was 12.35 months.

The most common adverse events were discharge around the catheter during placement, fatigue, bladder spasms, and micturition urgency.

In an accompanying editorial, Girish S. Kulkarni, MD, of Princess Margaret Cancer Center, the University of Toronto, Ontario, Canada, explains that BCG-unresponsive NMIBC is a "notoriously difficult to treat" condition for which nonsurgical treatment options are suboptimal. He said the findings by Boorjian and colleagues are encouraging.

"The reported efficacy, manageable adverse event profile, and straightforward dosing schedule all have the potential to make nadofaragene firadenovec the new gold standard for patients with BCG-unresponsive bladder cancer," Kulkarni writes. "At the very least, this study helps establish a new benchmark against which new therapies for this disease can be tested, thus enabling the conduct of future randomized studies."

Hope for Bladder Preservation

Kulkarni also notes that the results support "the oncological safety of an attempt at bladder preservation" in this patient population. Only 5.3% of patients experienced disease progression to muscle invasion during the study. Among those patients, salvage with cystectomy appeared feasible, he writes.

Senior study author Colin P. N. Dinney, MD, further emphasized the importance of the treatment for bladder preservation.

"Once patients with high-grade, non-muscle-invasive bladder cancer no longer benefit from their initial BCG treatments, patients often make an informed decision to decline cystectomy ― a highly complex and life-altering bladder removal surgery ― or are often medically ineligible for this complex operation, leaving them with limited options," Dinney explained in a press statement.

Treatment with this new gene therapy represents an effective alternative, he suggested.

"As a practicing urologist, I'm encouraged by these efficacy and safety data, which demonstrate the potential for a novel treatment option that fits within the urology practice and gives patients the choice of receiving treatment once every 3 months ― which may be a particularly important consideration in this evolving healthcare environment," said Gennady Bratslavsky, MD, president of the Society of Urologic Oncology Clinical Trials Consortium, which has worked with the manufacturer on the clinical trials of the product.

The study is ongoing; a 4-year treatment and monitoring phase is planned.

Boorjian has received consulting fees and personal fees from Ferring, FerGene, Sanofi, and ArTara. Dinney has used shared resources funded by a grant from the National Institutes for Health/National Cancer Institute at MD Anderson Cancer Center and has received grant and personal fees from FKD therapies. He also is a creator of intellectual property owned by UT/MDACC related to the use of genetic alterations as a predictive biomarker for response to nadofaragene firadenovec. Financial disclosures of several coauthors are available in the original article. Kulkarni has disclosed no relevant financial relationships.

Lancet Oncol. Published online November 27, 2020. Abstract, Editorial

Sharon Worcester is a reporter for MDedge News, part of the Medscape Professional Network.

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COMPLICATIONS OF CYTOREDUCTIVE NEPRHECTOMY

Patients with higher intraoperative blood loss and those treated at lower-volume surgical centers had a greater risk of high-grade complications after undergoing cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC), according to an analysis of registry data.

Higher intraoperative blood loss was also associated with low-grade postoperative complications. Intraoperative complications were more likely in patients who had concurrent thrombectomy and surgery on adjacent organs.

Eduard Roussel, MD, of University Hospitals Leuven (Belgium) and colleagues reported these findings in European Urology Oncology.

The authors noted that the role of CN in mRCC is controversial. With findings published in the New England Journal of Medicine, the CARMENA trial "shifted treatment paradigms" away from surgery by suggesting that sunitinib alone is noninferior to sunitinib after CN.

“Nonetheless, there is a general consensus that certain selected subgroups of patients with low-volume, single-site metastases and few adverse IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] criteria would still benefit from the continued use of upfront CN,” the authors wrote.

They advised clinicians to weigh the risks and benefits of CN, particularly because “postoperative morbidity might preclude or delay the use of subsequent systemic therapies.” However, the risk/benefit calculation for CN has been difficult because past investigations have tended to focus only on survival outcomes, so there isn’t much data on morbidity, the authors wrote.

Patient Characteristics and Complications

To investigate morbidity associated with CN, Dr. Roussel and colleagues reviewed data from the Registry of Metastatic RCC (REMARCC). The team analyzed the clinical records of 736 patients who underwent nephrectomy for mRCC during 1980-2019.

The patients’ median age was 63 years (range, 55-70 years), and about three-quarters were men. The majority had clear cell carcinoma, and the lungs were the most common site of metastases.

More than 97% of procedures were complete nephrectomies, and the rest were partial. The median estimated blood loss was 400 mL, and the median follow-up was 16.5 months.

There were 69 patients who had intraoperative complications, most commonly bleeding (n = 25), spleen laceration (n = 13), and vascular injury (n = 11).

There were 217 patients who had postoperative complications, including 45 patients with high-grade complications (grade 3-5) and 10 who died.

The most common postoperative complications were vascular/lymphatic in nature. These occurred in 67 patients and included 10 lymphoceles.

“[G]iven the relatively high rate of postoperative lymphoceles, which is probably attributable to the performance of lymph node dissections and the lack of proven oncological survival benefit thereof, surgeons might reconsider the performance of lymphadenectomy during CN,” the investigators wrote.

Other common postoperative complications included infectious and cardiopulmonary issues, which occurred in 42 and 39 patients, respectively.

Predictors of Complications

Thrombectomy and adjacent organ removal were significant predictors of intraoperative complications on multivariable analysis. The odds ratios were 1.38 (P = .009) for thrombectomy and 2.71 (P = .004) for adjacent organ removal.

Estimated blood loss was a significant predictor of low- and high-grade postoperative complications. The OR for high-grade complications per 200 mL of blood lost was 1.06 (P = .007), and the OR for low-grade complications per 200 mL blood lost was 1.09 (P = .001).

There was a strong inverse correlation with CN case load at each center and high-grade postoperative complications, which highlights “the impact of centralization of care on postoperative outcomes in complex surgical scenarios,” the investigators wrote. The OR per 25 cases was 0.88 (P = .04).

Results were largely the same when the analysis was limited to the 560 subjects treated since 2006, in the targeted therapy era, except that adjacent organ removal as a predictor of intraoperative complications did not quite reach statistical significance (P = .06).

The presurgery risk factors identified in this study should assist with presurgical counseling, said Zachery Reichert, MD, PhD, a genitourinary medical oncologist and assistant professor at the University of Michigan, Ann Arbor, who was not involved in this study.

“This is especially important for patients who require thrombectomy or adjacent organ removal or do not have access to a surgeon with high cytoreductive nephrectomy caseloads,” he said.

Dr. Reichert reported having no disclosures. There was no external funding for this study, and the investigators didn’t have any disclosures.

Eur Urol Oncol. 2020;3:523-9. Abstract

Contact M. Alexander Otto at: aotto@mdedge.com.

ESMO 2020-NIVO-CABOZATINIB FOR RENAL CANCER

Promoting to the front line two drugs normally used in rearguard action to treat advanced renal cell carcinoma (RCC) ― nivolumab (Opdivo) and cabozantinib (Cabometyx) ― doubled overall response rates and progression-free survival (PFS) and significantly improved overall survival (OS) compared with first-line sunitinib (Sutent), investigators in the Checkmate 9ER trial reported.

Median PFS among patients with advanced RCC, which was the trial’s primary endpoint, was 16.6 months with nivolumab plus cabozantinib, compared with 8.3 months with sunitinib, translating into a hazard ratio (HR) of 0.51 for the combination (P < .0001). The median follow-up was 18.1 months.

Median OS had not been reached in either arm at the time of data cutoff, but the survival curves at the time of the analysis clearly favored nivolumab-cabozatinib, with an HR for death of .060 (P = .0010), said Tony K. Choueri, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts.

"With expanding options in our patients with advanced RCC, the overall efficacy, safety, and quality-of-life benefit, as well as individual patient characteristics, are very important considerations when you select appropriate therapy," he said in a press briefing prior to his presentation of the data in a presidential symposium at the European Society of Medical Oncology (ESMO) Virtual Congress 2020.

Although the nivolumab-cabozantinib combination therapy looks good, however, it's late to the game, commented Dominik Berthold, MD, from the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, the invited discussant for the briefing.

"The question is, what's the only drawback of this trial? It's probably the fact that it's not first in class in this situation," he said.

Berthold noted that nivolumab-cabozantinib, if approved for the frontline setting, will join the combination of the tyrosine kinase inhibitor (TKI) axitinib (Inlyta) plus pembrolizumab (Keytruda), which, as previously reported, was associated with a nearly 50% reduction in the risk for death in the KEYNOTE-426 trial. This combination was approved by the US Food and Drug Administration (FDA) for the frontline setting in April 2019.

As shown in the CheckMate-214 study, the combination of the programmed cell death protein–1 (PD-1) inhibitor nivolumab with the CTLA-4 inhibitor ipilimumab (Yervoy) was associated with significantly higher objective response rates and OS rates compared with sunitinib. This combination was approved by the FDA in April 2018 as first-line therapy for patients with advanced intermediate- or poor-risk RCC.

CheckMate 9ER Details

A total of 651 patients with previously untreated advanced or metastatic RCC that had a clear cell component in all International Metastatic RCC Database Consortium risk groups were enrolled and randomly assigned to receive either intravenous nivolumab 240 mg every 2 weeks plus oral cabozantinib 40 mg daily or oral sunitinib 50 mg daily in cycles of 4 weeks on therapy/2 weeks off therapy. Patients were treated until disease progression or unacceptable toxicities occurred.

The primary PFS endpoint and the secondary OS endpoint both favored the combination, as did the objective response rate, which was 55.7% with nivolumab-cabozantinib vs 27.1% with sunitinib (P < .0001). Complete responses were seen in 8% of patients who received the combination vs 4.6% with the patients who received sunitinib. Partial responses were seen in 47.7% and 22.6%, respectively.

Patients generally tolerated the combination. The incidence of the most common high-grade treatment-emergent adverse events and other adverse events of any grade was similar to that seen with sunitinib, Choueri said.

The rates of treatment-related events that led to discontinuation was 3.1% among patients who received the combination, 5.6% among patients who received the nivolumab component only, and 6.6% among patients who received cabozantinib only. It was 8.8% among patients who received to sunitinib. More than 50% of patients in the combination arm needed a dose reduction of nivolumab-cabozantinib because of adverse events, however.

"Overall, it seems that the combination has somewhat a manageable safety profile in patients with advanced RCC," Choueri said.

Patient-reported quality of life, as measured by the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy–Kidney Symptom Index 19 total score, was an exploratory endpoint. It was maintained over time with the combination but deteriorated over time with sunitinib, with statistically significant differences between the study arms at most time points to 91 weeks, he reported.

Making Choices

Press briefing discussant Berthold acknowledged the benefit that having an additional therapy offers clinicians and patients.

"What we still need to learn here is, are there any patient populations who may benefit more on this combination compared with other combinations?," he said. "Cabozantinib is quite a unique TKI which may target better bone metastases, for example, so I think there are things we need to learn from further data and longer follow-up."

Camillo Porta, MD, from the University of Bari, Bari, Italy, the invited discussant for the presidential symposium, urged caution in comparing the three regimens, owing to differences in the drug used, study endpoints, baseline patient characteristics, and the distribution of patients among different prognostic groups.

When it comes to deciding between frontline regimens, "the only possible, though highly empiric, driver of our therapeutical choice should be the biological aggressiveness of the tumor," he said.

For patients with highly aggressive disease, the use of an immune checkpoint inhibitor plus a vascular endothelial growth factor receptor (VEGFR)–directed TKI may help control disease long enough to give the checkpoint inhibitor time to work.

"Otherwise, one could head for the long-term benefit of the immune combo as well as for complete responses, trying to spare [patients] the additional toxicities deriving from the continuous use of the VEGFR TKI," he added.

Porta noted that when considering the trade-off between efficacy and safety in the first-line setting, many patients are willing to accept more toxicities in exchange for clinical benefit.

The study was sponsored by Bristol-Myers Squibb. Choueri disclosed consultancy fees, advisory board activity, manuscript preparation, travel/lodging, honoraria, and grants for clinical trials from BMS and others. Berthold disclosed an advisory role for Ipsen, Bristol-Myers Squibb, Merck, and Pfizer. Porta disclosed advisory/consulting activities and speakers bureau participation for BMS and others.

European Society for Medical Oncology (ESMO) Annual Meeting 2020: Abstract 6960, presented September 19, 2020.

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URINE TEST FOR BLADDER CANCER

An assay using methylation markers may offer an alternative to more costly, invasive methods for bladder cancer (BCa) detection and surveillance, according to a new study.

"Urine tumor DNA methylation assessment for early diagnosis, minimal, residual tumor detection and surveillance in bladder cancer is a rapid, high-throughput, non-invasive and promising approach, which may reduce the burden of cystoscopy and blind second surgery," Dr. Tianxin Lin of Sun Yat-sen University in Guangzhou, China, and colleagues write in the Journal of Clinical Investigation.

About three-quarters of patients with BCa have non-muscle-invasive (NMIBC) disease, and most of these will recur, the authors note. Cystoscopy and cytology are the gold standard for monitoring patients, they add, although cytology has low sensitivity, particularly for low-grade disease.

While UroVysion fluorescence in situ hybridization (FISH) is more sensitive, it is also less sensitive for low-grade tumors. For patients with high-grade and T1 disease, repeated transurethral resection of bladder tumor (re-TURBT) is recommended, but there is currently no way to determine which patients have residual disease, according to the authors.

DNA-methylation assays tested in Europe have shown promise for monitoring BCa recurrence, they add, but have not been validated in large Asian cohorts.

The team developed the MassARRAY (utMeMA) using 26 markers identified from bladder tumors and normal tissue from three patient cohorts. Validation identified 25 methylation markers in tumor tissue and matched urine samples, but not in normal tissue, while 23 of the markers in urine were significantly correlated with matched tumor tissue.

The researchers trained and tested their diagnostic model in 313 samples and validated it in 175 samples.

A model with two of the markers had a sensitivity of 88% in the training dataset, 90% in the test dataset, and 92% in the validation dataset, with a specificity of 86%, 84% and 77%, respectively.

Among 251 BCa patients, utMeMA was four times as sensitive as cytology (69.2% vs. 16.0%) and three times more sensitive than FISH (69.2% vs. 22.2%) for detecting low-grade tumors. The model was also more sensitive than cytology or FISH for patients with Ta or T1 disease, high-grade disease or muscle-invasive bladder cancer. Cytology and FISH were more specific than uTMeMA, but not significantly so.

Forty-seven patients in the modeling and validation cohorts underwent re-TURBT, with samples available before surgery. Fifteen had residual tumor, which was correctly diagnosed by utMeMA in 14 patients (93%), versus three of 11 patients with cytology (27%) and nine of 14 with FISH (64%).

"Our approach achieved a great improvement in sensitivity over urine cytology and FISH, especially in the detection of early-stage, minimal, residual and recurrent tumors. Therefore, it is adopted in the optional clinical detection of BCa by more than 10 hospitals in China. A large-scale, multicenter and prospective clinical trial (NCT04314245) is ongoing to validate its clinical applicability in China," the authors write.

The authors report no conflicts of interest and no commercial funding.

Dr. Lin was not available for an interview by press time.

SOURCE: https://bit.ly/3hFdFZQ Journal of Clinical Investigation, online August 20, 2020.

CABOZATINIB FOR UROTHELIAL CARCINOMA

In a single-center phase II trial reported in The Lancet Oncology, Andrea Apolo, MD, and colleagues found that the multikinase inhibitor cabozantinib showed activity in a cohort of patients with platinum-refractory metastatic urothelial carcinoma.

Andrea Apolo, MD

As noted by the investigators, in addition to inhibiting the MET, VEGFR, AXL, and RET kinases, cabozantinib has an effect on the tumor immune microenvironment by decreasing regulatory T cells and myeloid-derived suppressor cells.

Study Details

The open-label, single-arm, three-cohort phase II trial involved 42 evaluable patients with metastatic platinum-refractory urothelial carcinoma enrolled at the National Cancer Institute between September 2012 and October 2015. Patients received 60 mg of cabozantinib orally once daily in 28-day cycles until disease progression or unacceptable toxicity.

The study also included two exploratory platinum-refractory cohorts: one consisting of 6 patients with bone-only urothelial carcinoma metastases, and the other made up of 13 patients with rare histologies of the genitourinary tract. In the main cohort, 64% of patients had received two or more prior therapies for metastatic disease.

Responses

Median follow-up was 61.2 months. In the main cohort, objective response was observed in eight patients (19%), including complete response in one. An additional 19 patients (45%) had stable disease. Median progression-free survival was 3.7 months (95% confidence interval [CI] = 3–6 months), with 6- and 12-month rates of 37% and 10%. Median overall survival was 8.1 months (95% CI = 5.2–10.3 months), with 6- and 12-month rates of 64% and 26%.

Bone response was observed in three of five evaluable patients in the cohort with bone-only metastatic disease. Among a total of 16 patients with urothelial carcinoma and bone metastases (from the main cohort and the exploratory cohort), median progression-free survival was 3.9 months and median overall survival was 7.2 months.

In biomarker analyses, treatment with cabozantinib reduced myeloid-derived suppressor cell populations, decreased the percentage of regulatory T cells in the CD4-positive T-cell population while increasing the ratio of effector CD8-positive T cells to regulatory T cells, and increased expression of PD-1 on regulatory T cells.

Adverse Events

Among all 68 patients who received cabozantinib, the most commonly reported grade 3 or 4 adverse events were fatigue (in 9% of patients), hypertension (7%), proteinuria (6%), and hypophosphatemia (6%). Serious adverse events included pulmonary embolism and rectovaginal fistula in one patient each.

Adverse events led to discontinuation of treatment in five patients (7%) due to grade 3 platelet decrease in one, grade 3 increase in aspartate aminotransferase in two, grade 3 proteinuria in one, and grade 1 transient ischemic attack (considered unrelated to treatment) in one. No treatment-related deaths were reported.

The investigators concluded, “Cabozantinib has single-agent clinical activity in patients with heavily pretreated, platinum-refractory metastatic urothelial carcinoma with measurable disease and bone metastases and is generally well tolerated. Cabozantinib has innate and adaptive immunomodulatory properties providing a rationale for combining cabozantinib with immunotherapeutic strategies.”

Dr. Apolo, of the Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, is the corresponding author for The Lancet Oncology article.

N+ RENAL CANCER SHOULD CLASSIFY AS STAGE IV?

The definition of stage IV renal cell carcinoma (RCC) should be expanded to include lymph node–positive stage III disease, according to a population-level cohort study published in Cancer.

While patients with lymph node–negative stage III disease had superior overall survival at 5 years, survival rates were similar between patients with node–positive stage III disease and stage IV disease. This supports reclassifying stage III node-positive RCC to stage IV, according to researchers.

"Prior institutional studies have indicated that, among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease," wrote Arnav Srivastava, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues.

The researchers used data from the National Cancer Database to identify patients with AJCC stage III or stage IV RCC who had undergone nephrectomy and lymph node dissection.

The cohort included 8,988 patients, 6,587 of whom had node–negative stage III disease, 2,218 of whom had node–positive stage III disease, and 183 of whom had stage IV metastatic disease. The researchers compared relative survival between staging groups.

The 5-year overall survival rate was 61.9% in patients with node–negative stage III RCC (95% confidence interval, 60.3%-63.4%), 22.7% in patients with node-positive stage III RCC (95% CI, 20.6%-24.9%), and 15.6% in patients with stage IV RCC (95% CI, 11.1%-23.8%).

"Patients with lymph node–positive stage III disease and those with stage IV disease were found to have overlapping 95% CIs when measuring 5-year survival; both demonstrated similar mortality," the researchers reported. They further noted that these findings remained unchanged when patients were stratified by clear cell and non–clear cell histology.

In an accompanying editorial, Daniel D. Shapiro, MD, of the University of Texas MD Anderson Cancer Center, Houston, and E. Jason Abel, MD, of the University of Wisconsin–Madison, said the study results suggest the clinical phenotype of patients with isolated lymph node metastases is different from other stage III RCCs.

"Future editions of the AJCC staging system [should] recognize the increased risk with [lymph node–positive stage III] tumors and consider reclassification of [these] tumors as stage IV tumors so that baseline risks are more accurately measured in these rare populations," they recommended.

Dr. Srivastava and colleagues acknowledged that two key limitations of the study were the retrospective design and the absence of data on other survival measures, such as metastasis-free and cancer-specific survival.

"Despite these limitations, we believe the current study was able to significantly build on prior work recommending the reclassification of lymph node–positive RCC as stage IV cancer," they concluded.

The National Cancer Institute supported the study. Some study authors disclosed relationships with pharmaceutical companies and other organizations for work performed outside of the current study. The editorial authors disclosed no conflicts of interest.

SOURCE: Srivastava A et al. Cancer. 2020 Jul 1;126(13):2991-3001.

This article originally appeared on MDedge.com.

FDA APPROVED MAINTENANCE AVELUMAB FOR METASTATIC UROTHELIAL CANCER

On June 30, the U.S. Food and Drug Administration (FDA) approved avelumab (Bavencio) for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.

JAVELIN Bladder 100

Efficacy of avelumab for the maintenance treatment of urothelial carcinoma was investigated in the JAVELIN Bladder 100 trial, a randomized, multicenter, open-label trial that enrolled 700 patients with unresectable, locally advanced, or metastatic urothelial carcinoma that had not progressed with four to six cycles of first-line platinum-containing chemotherapy. Patients were randomly assigned 1:1 to receive either avelumab intravenously every 2 weeks plus best supportive care or best supportive care alone. Treatment was initiated within 4 to 10 weeks after last chemotherapy dose. The main efficacy outcome measures were overall survival in all patients and in patients with PD-L1–positive tumors.

The median overall survival in all patients was 21.4 months in the avelumab arm and 14.3 months in the best supportive care alone arm (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.56–0.86, P = .001). Among patients with PD-L1–positive tumors (51%), the hazard ratio for overall survival was 0.56 (95% CI = 0.40–0.79, P < .001). In an exploratory analysis of patients with PD-L1–negative tumors (39%), the overall survival hazard ratio was 0.85 (95% CI = 0.62–1.18).

The most common adverse reactions reported in > 20% of patients who were treated with avelumab were fatigue, musculoskeletal pain, urinary tract infection, and rash. One patient died from sepsis, and 28% of patients had serious adverse reactions.

The recommended avelumab dose is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

The results from this study supported the conversion of accelerated approval of avelumab to a regular approval.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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ASCO 2020-IMMUNOTHERAPY RECHALLENGE FOR RENAL CELL CARCINOMA

In a study reported in the Journal of Clinical Oncology, Gul et al found that salvage therapy with nivolumab/ipilimumab was capable of producing a response after prior programmed cell death 1 (PD-1) pathway inhibitor therapy in some patients with metastatic renal cell carcinoma.

Study Details

The retrospective analysis included 45 patients from five U.S. centers who had not received prior anti–CTLA-4 antibody treatment. Overall, 76% had received an anti–PD-1 antibody and 24% received an anti–programmed cell death ligand 1 (PD-L1) antibody either alone or in combination with other therapies. Best overall response on anti–PD-1 therapy was partial response in 53% of patients, stable disease in 27%, and progressive disease in 20%.

Key Findings

Median follow-up was 12 months. Among 44 evaluable patients receiving salvage nivolumab/ipilimumab, partial response was observed in 9 (20%), stable disease in 7 (16%), and progressive disease in 28 (62%). 

Among 24 patients with a partial response to prior therapy, partial response was observed in 4, stable disease in 2, and progressive disease in 17 with salvage therapy. Among 12 patients with stable disease on prior therapy, 3 had partial response, 5 had stable disease, and 4 had progressive disease. Among nine patients with progressive disease on prior therapy, two had a partial response and seven had progressive disease.

Median duration of response was 7 months (range = 2–17 months) and median progression-free survival was 4 months (range = 0.8–19 months). Among nine patients with partial response, six had ongoing response and five were receiving maintenance nivolumab at the time of analysis.

Immune-related adverse events of any grade were observed in 64% of patients, with the most common being diarrhea (16%), rash (13%), hepatotoxicity (9%), and pneumonitis (7%). Grade 3 or 4 immune-related adverse events were observed in 13%, with the most common being hepatotoxicity (7%) and pneumonitis, rash, diarrhea, thrombocytopenia, and colitis (2% each). No treatment-related deaths were reported.

The investigators concluded, “Ipilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic renal cell carcinoma who had prior treatment with checkpoint inhibition.”

Brian I. Rini, MD, of Vanderbilt University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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ASCO 2020-IMMUNOTHERAPY RECHALLENGE FOR RENAL CANCER

Immunotherapy rechallenge in patients with metastatic renal-cell carcinoma (mRCC) appears to be safe and "reasonably efficacious," according to what is believed to be the largest study reporting on outcomes of immunotherapy rechallenge in this patient group.

Dr. Praful Ravi of Dana-Farber Cancer Institute in Boston reported the results May 29 during the American Society of Clinical Oncology (ASCO) 2020 virtual annual meeting, with simultaneous publication in JAMA Oncology.

Several immune-checkpoint inhibitors (ICIs) - nivolumab, ipilimumab, avelumab and pembrolizumab - are approved and widely used (alone or in combination) in patients with mRCC.

"Use of these agents has significantly improved outcomes. The median survival now approaches nearly four years in patients treated with frontline ipilimumab/nivolumab," Dr. Ravi said during his presentation.

"However, many, if not most patients treated with immunotherapy for kidney cancer ultimately progress. Oncologists may therefore attempt rechallenge with a checkpoint inhibitor," but the efficacy and safety of ICI rechallenge in mRCC is unknown, he added.

To investigate, a multicenter team of clinicians did a retrospective cohort study of 69 consecutive patients with mRCC from nine institutions in the U.S. who received at least two separate lines of ICI (ICI-1, ICI-2) between 2012 and 2019. The median age at diagnosis of mRCC was 61 years; nearly 90% had clear-cell histology.

The most common therapies received at ICI-1 were single-agent ICI (39%) or ICI in combination with targeted therapy (42%), while at ICI-2, the most common therapies were single-agent ICI (38%) or dual ICI (32%).

The most common reason for stopping ICI-1 was disease progression (72%), although about one in five stopped for toxic effects (23%).

Overall, among 68 evaluable patients at ICI-1, the response rate was 37%. Among 64 evaluable patients at ICI-2, the response rate was lower (23%).

Patients who responded at ICI-1 had a higher chance of responding at ICI-2 compared with those who had either stable disease or disease progression at ICI-1. The response at ICI-2 was higher in those who had stopped ICI-1 for toxicity, as opposed to those who had stopped due to disease progression, Dr. Ravi reported.

Nearly half of patients had some form of immune-related adverse event at ICI-2, Dr. Ravi said. Fewer patients suffered grade-3-or-higher immune-related adverse events at ICI-2 than ICI-1 (16% vs. 26%). There were no treatment-related deaths.

Summing up, Dr. Ravi said this study suggests that the response to ICI re-challenge is "around 20%, which is a reasonable number and not too dissimilar to that seen with single-agent avelumab in the second-line post-tyrosine-kinase setting. Responses were seen even with single-agent ICI at ICI-2, as well as in those who had not responded to prior line of ICI. Finally, ICI re-challenge appeared relatively safe. Going forward, we await data from prospective trials to see whether sequential use of immunotherapy has a role to play in kidney cancer."

This study had no specific funding, and Dr. Ravi has no relevant disclosures.

SOURCE: https://bit.ly/2XyigFW JAMA Oncology, online May 29, 2020.

MET INHIBITORS FOR PAPPILARY RENAL CANCER

Savolitinib appears to improve outcomes in patients with MET-driven papillary renal-cell carcinoma (PRCC) compared with sunitinib, the standard of care, according to results from the SAVOIR randomized clinical trial.

This is "proof of concept that a papillary RCC can have a subset that is MET-dependent," Dr. Toni K. Choueiri of Dana-Farber Cancer Institute and Harvard Medical School, in Boston, told Reuters Health by email. "We needed a targeted approach really badly in RCC, so we hope this is a start and a new trial will be more definitive."

In a phase-2 study of savolitinib in 109 patients with PRCC, eight of 44 (18%) patients who were determined to have MET-driven disease showed partial responses, compared with no responses among patients with MET-independent PRCC.

In the current phase-3 study, Dr. Choueiri and colleagues assessed the efficacy and safety of savolitinib versus sunitinib (the current standard-of-care treatment) in patients with MET-driven, unresectable and locally advanced or metastatic PRCC.

The study was halted prematurely after enrolling 60 patients because a concurrent retrospective molecular epidemiology study on the outcomes of patients with MET-driven PRCC on sunitinib suggested that MET-driven status did not appear to be a negative predictive factor for treatment outcomes. The researchers concluded that their trial would be unlikely to detect a difference in efficacy between the treatment groups and terminated recruitment.

Among those enrolled, 17 of 33 patients (52%) in the savolitinib group experienced progression events, compared with 20 of 27 patients (74%) in the sunitinib group, a difference that was not statistically significant.

Median progression-free survival (PFS) was 7.0 months in the savolitinib group versus 5.6 months in the sunitinib group, the researchers report in JAMA Oncology.

Nine patients (27%) in the savolitinib group and 13 patients (48%) and the sunitinib group died, a difference that fell short of statistical significance.

The overall response rate (ORR) was also nominally higher in the savolitinib group (9/33, 27%) than in the sunitinib group (2/27, 7%). All responses in both groups were partial.

None of the responding patients in the savolitinib group had disease progression as of the data cutoff, compared with one of the two responding patients in the sunitinib group.

Adverse events of any cause occurred with similar frequency in the two groups, and adverse events led to discontinuation in six patients in the savolitinib group versus five in the sunitinib group.

Disease progression was the most common reason for treatment discontinuation in both groups.

"I think overall it is impossible to make assertions because the study is underpowered and had to stop at 60 patients and did not enroll the full 180 patients," Dr. Choueiri said. "Nevertheless, we are encouraged by ORR differences, hazard ratio (HR) for PFS and HR for overall survival for a savolitinib, which is a tyrosine kinase inhibitor (TKI) specific against MET."

"We hope that now the field knows that a MET-targeted approach can work in a subset of papillary RCC where there is no standard," he said. "We hope to have a next trial with savolitinib, and that trial is appealing to the community and the patients and stays relevant with all the changes that are happening in the RCC field."

Dr. Mehmet Asim Bilen of Winship Cancer Institute of Emory University, in Atlanta, who recently reviewed PRCC and MET inhibitors, told Reuters Health by email, "Due to the early stop of this clinical trial and small sample size, we cannot make a definitive conclusion. However, the data suggest encouraging efficacy and safety profile of savolitinib over sunitinib in patients with MET-driven papillary RCC. Additionally, future studies of savolitinib are reasonable with other combinations such as immunotherapy."

"Most importantly, this is one of the first molecularly selected phase-3 clinical trials that were conducted in this rare subtype," he said. "Because of this reason, this study opened up an important door in the field and demonstrates that a similar trial can be conducted in the future."

"Overall, MET is an appealing drug target in genomically selected papillary RCC, and developing effective MET targeted therapies is needed in this patient population since they have worse outcomes," said Dr. Bilen, who was not involved in the research. "Therapeutic interventions targeted to the MET pathway in papillary RCC should resume alone or in combinations with other agents in order to improve patient outcomes."

AstraZeneca provided funding for the study, employed several authors and had financial ties to others, including Dr. Choueiri.

SOURCE: https://bit.ly/2XtMauR JAMA Oncology, online May 29, 2020.

ASCO 2020-NO ROLE OF ADJUVANT IMMUNOTHERAPY IN BLADDER CANCER?

"There is currently no role for adjuvant atezolizumab [Tecentriq, Genentech] in muscle-invasive bladder cancer," according to Daniel Y. C. Heng, MD, MPH, who was commenting on negative results from a phase 3 clinical trial.

"So why is there a benefit in the metastatic setting but not in this adjuvant setting?" he asked. "Why is there a benefit potentially or efficacy shown in the non–muscle-invasive setting but not in this adjuvant setting in muscle-invasive disease?"

Heng is staff medical oncologist at the Tom Baker Cancer Center in Calgary and a clinical associate professor of medicine at the University of Calgary, Canada.

He was discussing results from the IMvigor 010 trial, the first phase 3 adjuvant study of a checkpoint inhibitor in muscle-invasive urothelial cancer (MIUC). The trial failed to meet its primary endpoint of disease-free survival (DFS).

The results, which were presented at the virtual scientific program of the American Society of Clinical Oncology (ASCO) 2020 annual meeting, showed that the 18-month DFS rate was 51% for patients who received received atezolizumab and 49% for the observation arm.

"This was a completely negative trial with no disease-free benefit, and there was no disease-free benefit across all subgroups, including PD-L1," said Toni K. Choueiri, MD, the director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, Massachusetts. "There was no overall survival benefit at 22 months' follow-up, despite the fact that the regimen was tolerable."

Speaking at a "Highlights of the Day" session, Choueiri explained that the significance of these data is that a single-agent checkpoint inhibitor is not advised in unselected patients for the treatment of MIUC. "And this is despite having a high-risk population, like the one here, where over 50% were PN positive," he said. "There was an interesting hazard ratio trend for pT2, pT3, pT4 favoring some benefit in high-risk T stage, but I would not recommend it in these subgroups."

Heng noted that even in a subgroup analysis of PD-L1-positive patients, there was no benefit from atezolizumab compared to observation.

"Although it wasn't shown, those patients without prior neoadjuvant chemotherapy or negative pathologic node status did not show any difference either," said Heng, who was discussant for the paper.

Heng speculated as to whether the lack of efficacy in the adjuvant setting was because the gross tumor needs to be in situ to potentiate the immune response or whether all the drugs in the class are equal. "For example, is atezolizumab not as good as some of the other agents? I'm not sure," he said.What was interesting, he said, is that there might be a slight benefit for the T4 subset, although it wasn't statistically significant in the study. "I think that's a space to watch out for in future clinical trials of this disease to see whether or not the more higher-risk patients, the T4 disease patients, benefit from adjuvant immune checkpoint inhibitors," Heng said.

Study Details

Radical surgery with or without cisplatin-based neoadjuvant chemotherapy is the standard of care for MIUC, which continues to be a deadly disease despite treatments with curative intent. There is currently no conclusive level I evidence that adjuvant chemotherapy improves overall survival.

Up to half of all patients with MIUC are eligible for cisplatin-based chemotherapy, and atezolizumab has been approved as monotherapy for patients with multiple locally advanced or metastatic urothelial carcinoma.

"We hypothesized that adjuvant atezolizumab monotherapy would reduce the risk of recurrence or death after radical surgery," said lead author Maha H. A. Hussain, MD, professor of medicine and deputy director at the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine, Chicago, Illinois, who presented the primary analysis of the study.

A total of 809 patients were randomly assigned to receive either atezolizumab 1200 every 3 weeks for 16 cycles or 1 year of observation following radical cystectomy/nephroureterectomy with lymph node dissection within 14 weeks or less from registration.

Patients who had received neoadjuvant chemotherapy were required to have at a minimum pathologic T2 to T4a disease or node-positive disease. Others were required to have pathologic T3 or T4a disease or pathologic node-positive disease. Postsurgical radiotherapy or adjuvant chemotherapy was not permitted. If patients had not received prior neoadjuvant chemotherapy, they had to have either been ineligible for it or declined adjuvant cisplatin-based chemotherapy.

The primary endpoint was DFS; secondary endpoints included overall survival.

"In both arms, many patients came off protocol, primarily because of disease progression ― 59% of patients in the atezolizumab arm, and 77% in the observation arm," said Hussain. "However, more patients in the treatment arm came off because of adverse events ― 31%, compared to 3% in the observation arm."

Nearly half of patients had received prior neoadjuvant chemotherapy (48% of the ateozolizumab group and 47% of the observation arm). The population was considered to be at very high risk; almost 40% of patients in both arms had pathologic T3 or T4 disease, and 52% had node-positive disease.

In the intent-to-treat population, the median DFS was 19.4 months in the atezolizumab arm, compared to 16.6 months in the observation arm. This difference did not translate into a significant hazard ratio (0.89; P = .2446).

"The interim overall survival analysis is not mature at this moment, and the median overall survival has not been reached," said Hussain. "These data continue to be collected on all patients enrolled into the study in the intent-to-treat population."

Overall, the treatment was well tolerated, she noted. Treatment-related adverse events occurred in 71% of patients who received atezolizumab, and grade 3 or 4 events occurred in 16%. One grade 5 event was attributed to atezolizumab. Adverse events leading to discontinuation of atezolizumab occurred in 16% of the patients.

"IMvigor 010 did not meet its primary endpoint of disease-free survival," concluded Hussain. "There was no prespecified subgroup, including higher PD-L1 status, that showed treatment benefit with atezolizumab.”

She added that follow-up for overall survival is ongoing and that "additional exploratory biomarkers and subgroup analyses may warrant further study."

Clinical trials with atezolizumab as monotherapy and as combination treatment are underway in a variety of disease settings for patients with urothelial carcinoma.

The study was funded by F. Hoffmann-La Roche Ltd. Hussain, Heng, and Choueiri have disclosed relationships with a large number of pharmaceutical companies.

American Society of Clinical Oncology (ASCO) 2020: Abstract 5000. Presented May 31, 2020.

Follow Medscape Oncology on Twitter for more cancer news: @MedscapeOnc.

ASCO 2020-MAINTENACE AVELUMAB FOR METASTATIC UROTHELIAL CANCER

Maintenance therapy with avelu­mab and best supportive care significantly prolonged overall survival vs best supportive care alone in patients with advanced urothelial carcinoma that did not progress on first-line platinum-based chemotherapy, according to an interim analysis of the phase III JAVELIN Bladder 100 trial. The survival benefit was observed among all patients enrolled in the trial, in patients who were programmed cell death ligand 1 (PD-L1)-positive, and in all prespecified subgroups. The data were presented during a press briefing in advance of the ASCO20 Virtual Scientific Program and during the virtual Plenary Session.¹

“This study met its primary objective, demonstrating significantly prolonged overall survival with first-line maintenance avelumab and best supportive care vs best supportive care alone in the overall population and in PD-L1–positive patients whose disease did not progress on platinum-based chemotherapy. Avelumab as first-line maintenance therapy represents a new first-line standard of care for advanced urothelial cancer that has not progressed on first-line platinum-based chemotherapy.” 
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“This study met its primary objective, demonstrating significantly prolonged overall survival with first-line maintenance avelumab and best supportive care vs best supportive care alone in the overall population and in PD-L1–positive patients whose disease did not progress on platinum-based chemotherapy. Avelumab as first-line maintenance therapy represents a new first-line standard of care for advanced urothelial cancer that has not progressed on first-line platinum-based chemotherapy,” said lead author Thomas Powles, MD, PhD, of Barts Cancer Institute, London.

“The maintenance setting is an attractive time for using a checkpoint inhibitor. Patients have gone through chemotherapy, and the disease is under control. But instead of waiting for disease to progress after chemotherapy—which it will quickly do in patients with advanced urothelial cancer—adding avelumab significantly improves survival,” he continued.

Patients with advanced urothelial cancer who respond to first-line platinum-based chemotherapy typically relapse eventually, and theoretically, maintenance therapy can prolong progression-free survival. JAVELIN Bladder 100 is the first maintenance trial to show a survival advantage in patients with advanced urothelial cancer with stable disease or better after first-line chemotherapy. 

Avelumab is a PD-L1 inhibitor approved for the treatment of advanced urothelial cancer that has progressed on platinum-based chemotherapy. The immune checkpoint inhibitor is also approved for renal cell carcinoma and Merkel cell carcinoma.

Study Details

JAVELIN Bladder 100 is a randomized phase III trial that enrolled patients with unresectable locally advanced or metastatic urothelial cancer without disease progression who had a response or stable disease after being treated in the first line with four to six cycles of gemcitabine/cisplatin or gemcitabine/carboplatin. Patients were randomly assigned 1:1 to receive maintenance avelu­mab at 10 mg/kg intravenously every 2 weeks plus best supportive care vs best supportive care alone. Treatment was continued until disease progression, toxicity, or death.

The primary endpoint was overall survival in all 700 randomly assigned patients and in 358 patients (51%) with PD-L1–positive tumors according to the Ventana SP263 assay. Results were stratified according to best response to first-line chemotherapy (complete response, partial response, or stable disease) and by visceral vs nonvisceral disease at the time of initiating first-line chemotherapy.

Patients were followed for 19.6 months in the avelumab group and 19.2 months in the best supportive care–alone group. The combination of avelumab plus best supportive care significantly prolonged overall survival by 31% (P =.001) vs best supportive care alone. The median overall survival was 21.4 months vs 14.3 months, respectively—a 7-month gain.

Among patients with PD-L1–positive tumors, survival was significantly prolonged by 44% (P = .001). In this group, the median overall survival was not reached for avelumab-treated patients vs 17.1 months for the best supportive care–alone group. All prespecified subgroups had an overall survival benefit from avelumab, including age, Eastern Cooperative Oncology Group performance status, first-line chemotherapy regimen, best response to chemotherapy, site of baseline metastasis, creatinine clearance, and PD-L1 status.

Adverse events of any grade occurred in 98% of avelumab recipients vs 77% in the best supportive care–alone group. Grade 3 or higher events—most frequently urinary tract infection, anemia, hematuria, fatigue, and back pain—were reported in 47.4% vs 25.2%, respectively.

DISCLOSURE: The study was funded by Pfizer as part of an alliance between Pfizer and Merck KGaA, Darmstadt, Germany. Dr. Powles has received honoraria from AstraZeneca, Bristol-Myers Squibb, Ferring, GLG Group, Janssen, Merck, Novartis, Pfizer, Roche/Genentech, and Seattle Genetics/Astellas; has served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Incyte, Ipsen, Merck, Novartis, Pfizer, and Seattle Genetics; has received research funding from AstraZeneca/MedImmune and Roche/Genentech; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca, Bristol-Myers Squibb, Ferring, MSD, Novartis/Ipsen, Pfizer, Research to Practice, and Roche/Genentech.

REFERENCE

1. Powles T, et al: Maintenance avelumab + best supportive care (BSC) vs BSC alone after platinum-based first-line chemotherapy in advanced urothelial carcinoma. ASCO20 Virtual Scientific Program. Abstract LBA1. Presented in premeeting press briefing on May 26, 2020.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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ASCO 2020-HIF2A INHIBITOR FOR VHL RENAL CARCINOMA

In an international trial, treatment with MK-6482, a small-molecule inhibitor of hypoxia-inducible factor (HIF)-2a, was well tolerated and resulted in clinical responses for patients with von Hippel-Lindau disease–associated renal cell carcinoma (RCC).

Eric Jonasch, MD

The results of the phase II trial were shared in today’s Genitourinary Cancer Oral Abstract Session during the ASCO20 Virtual Scientific Program by principal investigator Eric Jonasch, MD, Professor of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center (Abstract 5003).

von Hippel-Lindau Disease–Associated RCC

von Hippel-Lindau disease is a rare inherited mutation of the VHL gene. RCC affects approximately 40% of people with von Hippel-Lindau disease and is one of the most common causes of disease-related death.

The VHL mutation causes cells to lose their ability to respond to oxygen levels properly and leads to a buildup of HIF proteins inside the tumor cell. This process incorrectly signals that the cells are starved of oxygen, causing the formation of blood vessels and driving tumor growth. The inactivation of the VHL tumor-suppressor protein is also observed in more than 90% of sporadic RCC tumors. MK-6482 directly targets HIF-2a, hindering cancer cell growth, spread, and abnormal blood vessel development.

Treatment of von Hippel-Lindau disease–associated renal tumors consists of active surveillance until surgery is required for tumors larger than 3 cm to prevent metastatic disease. Repeated surgical procedures can carry significant complications as many patients develop renal insufficiency.

“Therapy options that can delay or avoid the need for surgery by decreasing tumor size are needed,” said Dr. Jonasch. “This agent could profoundly change the way we manage lesions in patients with von Hippel-Lindau disease.”

Methods

As of data cut-off, the single-arm clinical trial had enrolled 61 adult patients with a germline mutation diagnosis of von Hippel-Lindau disease, no prior systemic cancer therapy, measurable nonmetastatic RCC tumors, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Patients received MK-6482 orally once daily until disease progression, unacceptable toxicity, or investigator’s or patient’s decision to withdraw. Tumor size was evaluated at screening and every 12 weeks thereafter. No patients had progressive disease on treatment and 58 patients (95.1%) remain on treatment.

Results

The trial met its primary endpoint and showed an objective response rate in RCC tumors per RECIST by independent review. The confirmed response rate was 27.9%. When also considering the eight patients with unconfirmed response, the objective response rate was 41.0%. Additionally, 86.9% of patients had a decrease in the size of their target lesions. The median time to response was 5.5 months.

Most treatment-related adverse events were grade 1 or 2. Grade 3 adverse events occurred in 9.8% of patients. There were no grade 4 or 5 treatment-related adverse events reported. The most common adverse events were anemia (86.9%), fatigue (57.4%), headache (36.1%), dizziness (31.1%), and nausea (24.6%). Anemia was safely managed with long-acting erythropoietin injections.

“Patients with von Hippel-Lindau disease are at risk of developing several types of cancer and other tumors, and there are currently no approved therapies,” said Dr. Jonasch in a statement. “We are encouraged by the results of this clinical trial and look forward to seeing further study of MK-6482 as we work to make this treatment option available for patients with von Hippel-Lindau disease.”

“MK-6482 was well tolerated and had few side effects,” he continued. “This is the first therapeutic agent that has shown the efficacy and safety required to make it a real option for the management of patients with von Hippel-Lindau disease.”

Future studies to be considered include testing whether MK-6482 can prevent the development of new lesions in patients with von Hippel-Lindau disease.

Disclosure: Funding for this research was provided by Peloton Therapeutics, Inc., a wholly owned subsidiary of Merck & Co., Inc. For full disclosures of the study authors, visit coi.asco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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