A NOVEL REGIMEN FOR OVARIAN CANCER

In a single-institution phase II trial reported in JAMA Oncology, Zsiros et al found that the combination of pembrolizumab with bevacizumab and oral metronomic cyclophosphamide produced objective response in approximately half of women with recurrent ovarian cancer taking part in the study. Moreover, the combination produced clinical benefit in nearly all patients.

Study Details

In the trial, 40 women with recurrent platinum-sensitive, platinum-resistant, or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were enrolled at Roswell Park Comprehensive Cancer Center between September 2016 and June 2018. Patients had to have measurable disease on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Treatment consisted of pembrolizumab at 200 mg and bevacizumab at 15 mg/kg every 3 weeks plus oral cyclophosphamide at 50 mg once daily during the treatment cycle until disease progression or unacceptable toxicity.

Overall, 30 women (75%) had platinum-resistant disease, 14 (35%) had prior exposure to bevacizumab, and 19 (47.5%) had PD-L1–positive tumors (PD-L1 expression ≥ 1%).

KEY POINTS

• Objective response was achieved in 47.5% of patients.
• The clinical benefit rate was 95.0%.

Responses and Progression-Free Survival

Objective response on irRECIST was observed in 19 patients (47.5%), with complete response in 3 (7.5%). Responses were observed in 6 (60.0%) of 10 patients with platinum-sensitive disease and 13 (43.3%) of 30 (including the 3 complete responses) with platinum-resistant disease; responses were observed in 10 (52.6%) of 19 with PD-L1–positive disease and in 6 (35.3%) of 17 with PD-L1–negative disease. An additional 19 patients (47.5%) had stable disease, yielding a clinical benefit rate of 95.0%. The median duration of response was 8.3 months (interquartile range = 4.2–15.6 months) among patients with objective response and 5.9 months among all patients with clinical benefit, with response lasting > 12 months in 10 patients (25% of total population).

The median follow-up was 25.5 months. Median progression-free survival among all patients was 10.0 months (90% confidence interval [CI] = 6.5–17.4 months). Median progression-free survival was not reached in patients with complete response, 10.6 months in those with partial response, 20.2 months in those with platinum-sensitive disease, and 7.6 months in those with platinum-resistant disease.

Adverse Events

The most common treatment-related adverse events of any grade were fatigue (45.0%), diarrhea (32.5%), and hypertension (27.5%). Treatment-related grade ≥ 3 adverse events occurred in 32.5% of patients, with the most common being hypertension (15.0%) and lymphopenia (7.5%). Treatment-related adverse events led to discontinuation of treatment in 10% of patients, most commonly due to grade 2 skin toxicity. No treatment-related deaths were reported.

The investigators concluded, “In this phase II nonrandomized clinical trial, the combination of pembrolizumab with bevacizumab and oral cyclophosphamide was well tolerated and demonstrated clinical benefit in 95.0% and durable treatment responses (> 12 months) in 25.0% of patients with recurrent ovarian cancer. This combination may represent a future treatment strategy for recurrent ovarian cancer.”

Emese Zsiros, MD, PhD, of the Department of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by Merck & Co through the support of the Merck Investigator Studies Program. For full disclosures of the study authors, visit jamanetwork.com.

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®.

---

DO NOT RETREAT OVARIAN CANCER WITH PARP INHIBITORS

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What's not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

"Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats," the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.

Which Drug, Which Setting, Which Dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O'Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

"Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting," O'Cearbhaill said in an interview. "It is quite complicated to know which PARP inhibitor should be used in which setting and which patients."

"We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we're careful not to use PARP inhibitors in settings where there is little or no data," added O'Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

"Reescalation or resumption of the initial dose is never recommended," the guidelines state.

Retreatment

O'Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That's one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to O'Cearbhaill.

"Even if a high proportion of patients aren't ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients," she said. "It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer."

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Tew and Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. O'Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

AVASTIN FOR OVRAIAN STROMAL TUMORS?

In the phase II ALIENOR trial reported in JAMA Oncology, Isabelle Ray-Coquard, MD, and colleagues found that the addition of bevacizumab to paclitaxel did not improve the 6-month progression-free rate among women with relapsed ovarian sex cord–stromal tumors.

Isabelle Ray-Coquard, MD

Study Details

The study, performed in collaboration with the Rare Tumor committee of the Gynecologic Cancer InterGroup, included 60 women with sex cord–stromal tumors that had relapsed after at least one platinum-based chemotherapy from sites in France, Germany, Italy, Japan, and Belgium. Patients were randomly assigned to receive:

• Paclitaxel at 80 mg/m2 on days 1, 8, and 15 every 4 weeks alone for six cycles (n = 32)
• Paclitaxel with bevacizumab at 10 mg/kg on days 1 and 15 every 4 weeks for six cycles followed by maintenance bevacizumab (15 mg/kg every 3 weeks) for up to 1 year or until progression or unacceptable toxicity (n = 28).

Crossover to bevacizumab was permitted after progression during or following paclitaxel alone.

The primary outcome measure was 6-month progression-free rate. The trial used an adaptive Bayesian design, in which the combination group would be superior to the paclitaxel group if the probability of superiority was ≥ 90% at final analysis. Enrollment occurred between 2013 to 2016 and the final analysis database lock was in March 2020.

Six-Month Progression-Free Rate

Median follow-up was 38.9 months.

The estimated 6-month progression-free rate was 71% (95% credible interval = 55%–84%) with paclitaxel alone and 72% (95% credible interval = 55%–87%) with paclitaxel/bevacizumab. The Bayesian estimate for the probability that the 6-month progression-free rate distribution was higher with the combination was 57%, which was less than the predefined superiority threshold.

The objective response rate was 25% with paclitaxel alone vs 44% with the combination, with median response durations of 18.0 months vs 15.9 months. Median progression-free survival was 14.7 months vs 14.9 months, with Kaplan-Meier estimated 6-month rates of 72% vs 78%. Kaplan-Meier estimates of overall survival were 94% vs 93% at 1 year and 87% vs 73% at 2 years.

KEY POINTS

• The addition of bevacizumab to paclitaxel did not improve the 6-month progression-free rate.
• The estimated 6-month progression-free rate was 71% with paclitaxel and 72% with paclitaxel/bevacizumab.

Among the 16 patients who crossed over to bevacizumab after progression, median progression-free survival from start of bevacizumab was 6.9 months, with 3 patients having responses of ≥ 12 months.

Adverse Events

The most common adverse events of any grade were hypertension, fatigue, and neuropathy, with bleeding and proteinuria being more common in the combination group. The most common grade ≥ 3 adverse events were hypertension, infection, and neutropenia. No gastrointestinal perforations were observed. Adverse events led to discontinuation of treatment within 6 months in one patient in the combination group.

The investigators concluded, “Weekly paclitaxel is a new option for relapsed sex cord–stromal tumors. In this international randomized clinical trial of patients with relapsed sex cord–stromal tumors unsuitable for surgery, adding bevacizumab to weekly paclitaxel does not improve clinical benefit…. To our knowledge, this is the first randomized trial in sex cord–stromal tumors, and it establishes weekly paclitaxel as standard-of-care therapy after platinum-based therapy in this setting.”

Dr. Ray-Coquard, of Centre Léon Bérard, Université Claude Bernard Lyon, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by Roche. For full disclosures of the study authors, visit jamanetwork.com.

UPFRONT CHEMOTHERAPY FOR OVARIAN CANCER

Chemotherapy before cytoreductive surgery does not appear to worsen survival in women with advanced-stage epithelial ovarian cancer, according to findings from the National Cancer Database (NCDB).

"While this association doesn't prove the safety of upfront chemotherapy, it is concordant with the randomized-trial data and certainly suggests that no evidence of harm can be measured on the population level," Dr. Alexander Melamed of Columbia University Vagelos College of Physicians and Surgeons and New York-Presbyterian/Columbia University Irving Medical Center, in New York City, told Reuters Health by email.

"There are now four randomized trials that show starting treatment with chemotherapy results in equivalent long-term cancer outcomes and less surgical morbidity," he said. "Nonetheless, some opinion leaders in gynecologic oncology have worried that too frequent use of this approach could harm patients."

Dr. Melamed and colleagues used NCDB data to examine and compare time trends in the use of neoadjuvant chemotherapy and median survival among women with advanced-stage epithelial ovarian cancer in the U.S.

Among more than 72,000 women treated between 2004 and 2016, 73.5% were treated with primary cytoreductive surgery and 26.5% were treated with neoadjuvant chemotherapy.

The frequency of primary chemotherapy began increasing by 7.9% per year from 2006 to 2011, and after the first of the randomized trials showing a reduction in surgical morbidity and women assigned to neoadjuvant chemotherapy, the use of neoadjuvant chemotherapy accelerated by 10.3% per year from 2011 to 2016.

By 2016, 45.1% of women received chemotherapy as their initial treatment.

Between 2004 and 2013, median survival increased from 31.1 months to 37.8 months, an increase of 2.1% per year. But changing trends in the use of neoadjuvant chemotherapy were not associated with a change in median survival trend, the researchers report in JAMA Network Open.

Results were similar in a subgroup analysis restricted to women with high-grade serous carcinoma.

"Those surgeons who have continued to worry about the negative impacts of upfront chemotherapy on outcomes in ovarian-cancer patients can be reassured by these data," Dr. Melamed said. "While this study cannot itself demonstrate causality, it adds to the accumulating evidence of the safety of upfront chemotherapy in this setting."

SOURCE: https://bit.ly/33aeeGl JAMA Network Open, online September 25, 2020.

Reuters Health Information © 2020 

PROGNOSTIC GENE SIGNATURE FOR OVARIAN CANCER?

A new gene expression signature could improve on conventional risk factors when it comes to estimating prognosis and selecting treatment in patients with high-grade serous ovarian cancer, according to a study published in Annals of Oncology.

"Gene expression signature tests for prognosis are available for other cancers, such as breast cancer, and these help with treatment decisions, but no such tests are available for ovarian cancer," senior investigator Susan J. Ramus, PhD, of Lowy Cancer Research Centre, University of NSW Sydney, commented in an interview.

Dr. Ramus and associates developed and validated their 101-gene expression signature using pretreatment tumor tissue from 3,769 women with high-grade serous ovarian cancer treated on 21 studies.

The investigators found this signature, called OTTA-SPOT (Ovarian Tumor Tissue Analysis Consortium–Stratified Prognosis of Ovarian Tumors), performed well at stratifying women according to overall survival. Median overall survival times ranged from about 2 years for patients in the top quintile of scores to more than 9 years for patients in the bottom quintile.

Moreover, OTTA-SPOT significantly improved prognostication when added to age and stage.

"This tumor test works on formalin-fixed, paraffin-embedded tumors, as collected routinely in clinical practice," Dr. Ramus noted. "Women predicted to have poor survival using current treatments could be included in clinical trials to rapidly get alternative treatment. Many of the genes included in this test are targets of known drugs, so this information could lead to alternative targeted treatments.

"This test is not ready for routine clinical care yet," she added. "The next step would be to include this signature as part of a clinical trial. If patients predicted to have poor survival are given alternative treatments that improve their survival, then the test could be included in treatment decisions."

Study Details 

Dr. Ramus and colleagues began this work by measuring tumor expression of 513 genes selected via meta-analysis. The team then developed a gene expression assay and a prognostic signature for overall survival, which they trained on tumors from 2,702 women in 15 studies and validated on an independent set of tumors from 1,067 women in 6 studies.

In analyses adjusted for covariates, expression levels of 276 genes were associated with overall survival. The signature with the best prognostic performance contained 101 genes that were enriched in pathways having treatment implications, such as pathways involved in immune response, mitosis, and homologous recombination repair.

Adding the signature to age and stage alone improved prediction of 2- and 5-year overall survival. The area under the curve increased from 0.61 to 0.69 for 2-year overall survival and from 0.62 to 0.75 for 5-year overall survival (with nonoverlapping 95% confidence intervals for 5-year survival).

Each standard deviation increase in the gene expression score was associated with a more than doubling of the risk of death (hazard ratio, 2.35; P < .001).

The median overall survival by gene expression score quintile was 9.5 years for patients in the first quintile, 5.4 years for patients in the second, 3.8 years for patients in the third, 3.2 years for patients in the fourth, and 2.3 years for patients in the fifth.

This study was funded by the National Institutes of Health/National Cancer Institute, the Canadian Institutes for Health Research, and the Department of Defense Ovarian Cancer Research Program. Some of the authors disclosed financial relationships with a range of companies. Dr. Ramus disclosed no conflicts of interest.

SOURCE: Millstein J et al. Ann Oncol. 2020 Sep;31(9):1240-50.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

NO BENEFIT OF MEK INHIBITORS IN LOW GRADE OVARIAN CANCER

As reported in the Journal of Clinical Oncology by Bradley J. Monk, MD, and colleagues, the phase III MEK Inhibitor in Low-Grade Serous Ovarian Cancer (MILO)/ARRAY-162-311/ENGOT-ov11 trial showed that the MEK1/2 inhibitor binimetinib did not improve progression-free survival vs physician’s choice of chemotherapy in women with recurrent or persistent low-grade serous ovarian carcinomas. The trial was stopped early due to futility.

Bradley J. Monk, MD

Study Details

In the open-label trial, a total of 303 patients from sites in 20 countries had been randomly assigned 2:1 to receive binimetinib at 45 mg twice daily (n = 201) or physician’s choice of chemotherapy (n = 102) at the time of interim analysis in January 2016.  Patients had to have recurrent measurable low-grade serous ovarian carcinomas after one or more prior platinum-based chemotherapy but three or fewer prior chemotherapy lines. The primary endpoint was progression-free survival on blinded independent central review.

Progression-Free Survival

At interim analysis, median progression-free survival was 9.1 months (95% confidence interval [CI] = 7.3–11.3 months) in the binimetinib group vs 10.6 months (95% CI = 9.2–14.5 months) in the physician’s choice group (hazard ratio [HR] = 1.21, 95% CI = 0.79–1.86). Based on a futility boundary of hazard ratio > 0.84 for the 103 events that occurred at the time of interim analysis, the futility boundary was considered crossed, indicating a low probability of reaching statistical significance in favor of binimetinib with continued follow-up. The study was thus closed early after a total of 341 patients had enrolled.

On investigator assessment, median progression-free survival was 12.5 months (95% CI = 9.1–17.7 months) vs 11.6 months (95% CI = 10.0–16.1 months), with a hazard ratio of 0.87 (95% CI = 0.56–1.34). Overall response rate was 16% vs 13% and median duration of response was 8.1 months (range = 0.03–≥ 12.0 months) vs 6.7 months (range = 0.03–≥ 9.7 months). Median overall survival was 25.33 months (95% CI = 18.46 months–not reached) vs 20.83 months (95% CI = 17.45 months–not reached), with a hazard ratio of 0.85 (95% CI = 0.49–1.48).

Results for efficacy endpoints from an updated analysis in January 2019 among the total of 334 enrolled patients were consistent with results on interim analysis. 

A post hoc analysis suggested an association of presence of a KRAS mutation and response to binimetinib. KRAS mutation was present in 32% of patients in the binimetinib group and 34% of patients in the physician’s choice group.

Presence of KRAS mutation was significantly associated with response to treatment with binimetinib (odds ratio [OR] = 3.4, P = .003) but not physician’s choice of chemotherapy (OR = 2.13, P = .2). In the binimetinib group, objective response was observed in 44% of patients with KRAS mutation vs 19% of those with wild-type KRAS (P = .004). Compared with wild-type KRAS, KRAS mutation was also associated with prolonged progression-free survival in the binimetinib group (median = 17.7 months vs 10.8 months, P = .006) but not in the physician’s choice of chemotherapy group (median = 14.6 months vs 11.5 months, P = .502).

Adverse Events

Grade ≥ 3 adverse events occurred in 76% of patients in the binimetinib group and 44% of those in the physician’s choice of chemotherapy group, with the most common in the binimetinib group being increased creatine kinase (26%). Adverse events led to treatment discontinuation in 31% vs 17% of patients, with those leading to discontinuation in five or more patients in the binimetinib group consisting of decreased ejection fraction in eight (4%), vomiting in six (3%), and intestinal obstruction and retinal vein occlusion in five patients each (2%).

The investigators concluded: “Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary endpoint, binimetinib showed activity in [patients with] low-grade serous ovarian carcinomas across the efficacy endpoints evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib.”

Dr. Monk is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019, and was also supported by the National Cancer Institute, Cycle for Survival, and Ovarian Cancer Research Fund Alliance. 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®.

---

STATINS REDUCE OVARIAN CANCER MORTALITY?

 In a large observational study of women with epithelial ovarian cancer, use of a cholesterol-lowering statin was associated with a significant reduction in ovarian-cancer-specific mortality and the benefit was greatest in those taking a lipophilic statin.

"Statins inhibit the first enzyme in the mevalonate pathway. Products of the pathway have been implicated in tumorigenesis, including tumor growth, proliferation, and angiogenesis. Lipophilic statins also demonstrate prominent immunologic effects and can impact immunosurveillance," said lead researcher Dr. Kala Visvanathan at a press briefing held during the American Association for Cancer Research (AACR) second virtual annual meeting.

The few small studies that have evaluated statins and mortality in ovarian-cancer patients have shown mixed results, said Dr. Visvanathan, with Johns Hopkins Bloomberg School of Public Health and Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland.

To investigate further, the researchers linked data from the Finnish national cancer registry to prescription claims for women diagnosed with ovarian cancer between 1995 and 2015. Of the more than 10,000 women included in the analysis, 2,621 used statins for a median of 7.5 years.

During median follow-up of four years, use of any statin - lipophilic (such as simvastatin or lovastatin) or hydrophilic (such as pravastatin or rosuvastatin) - was associated with a 40% reduction (range 34% to 46%) in ovarian-cancer mortality compared with never use.

Lipophilic statins specifically were associated with a 43% reduction (95% confidence interval, 24% to 57%) in ovarian-cancer mortality (range, 24% to 57%) and there was a trend toward greater reduction in mortality with increasing dose (P trend = 0.06).

Lipophilic-statin use was associated with a reduction in ovarian-cancer death among all tumor subtypes, but the magnitude of reduction varied.

The most significant reductions in mortality occurred in those with endometrioid ovarian cancer and high-grade serous carcinoma (50% and 40% reduction in mortality, respectively).

In her presentation, Dr. Visvanathan noted that the five-year survival rate for ovarian cancer in the U.S. and other developed countries "remains less than 15%. There are no proven screening strategies, and there's an urgent need to find cheaper effective treatment alternatives."

"Our results support further clinical evaluation of lipophilic statins in women with epithelial ovarian cancer in a randomized controlled trial in conjunction with existing therapies. Our results also reinforce the value of examining existing therapies that are well tolerated and inexpensive to reduce global cancer burden," Dr. Visvanathan concluded.

Briefing co-moderator Dr. Antoni Ribas of the University of California, Los Angeles, said the observation of reduced ovarian-cancer-specific mortality with statin therapy is "provocative and needs to be validated with a prospective randomized trial and the data provides a justification for starting such a study."

The study had no commercial funding and the authors have disclosed no relevant conflicts of interest. SOURCE: https://bit.ly/2B2pTfa American Association for Cancer Research 2020 Virtual Annual Meeting II, presented June 22, 2020.

ASCO 2020-SURVIVAL DATA WITH OLAPRIB IN SOLO-2 (mBRCA-OVARIAN CANCER)

Women with platinum-sensitive relapsed ovarian cancer and a BRCA mutation could see their survival extended by over a year by maintenance therapy with the PARP-inihibitor olaparib (Lynparza, AstraZeneca).

The new overall survival (OS) data come from the SOLO2 study and were described as "a significant advance" in a cancer "that has a historically poor prognosis" by Richard Schilsky, MD, senior vice president and chief medical officer of the American Society of Clinical Oncology.

The results were highlighted at a presscast prior to being presented during the virtual scientific program of the 2020 ASCO annual meeting.

The SOLO2 study randomly assigned almost 300 women with relapsed BRCA-related ovarian cancer that was responding to platinum-based chemotherapy to maintenance therapy with either olaparib or placebo.

Earlier results from this study showed that olaparib was associated with an investigator-assessed progression-free survival (PFS) of 19.1 months, vs just 5.5 months with placebo, as previously reported by Medscape Medical News. 

New data from this trial, presented by Andrés Poveda, MD, Initia Oncology, Hospital Quironsalud, in Valencia, Spain, show that olaparib improved median OS by 12.9 months compared to placebo (51.7 months with olaparib vs 38.8 months with placebo; hazard ratio, 0.74; P = .054).

At 5 years' follow-up, 42.1% of women taking olaparib were alive, vs 33.2% taking placebo.

In an ASCO press release, Poveda described the improvement in median OS with olaparib as "impressive" and that it offers a "substantial benefit to our patients.

"This study helps usher in a new era of personalized medicine for women with this difficult-to-treat cancer," he added.

Poveda told reporters that this study is "the first randomized phase 3 trial to provide overall survival data for maintenance PARP inhibitors.

"The finding that 22% of patient in the olaparib group received the study treatment for more than 5 years is unprecedented in the setting of relapsed ovarian cancer," he added.

The new OS data were welcomed by Konstantin Zakashansky, MD, director of gynecologic oncology at Mount Sinai West, New York City, who was not involved in the study.

"PARP inhibitor trials have revolutionized therapy for ovarian cancer in the front line, as well as in the recurrent setting, [with] all of the recently presented trials showing significant improvement in progression free survival," he said.

"Overall survival data, however, which is considered the most clinically relevant endpoint in oncology trials and remains the 'gold standard' because of its relevance and objectivity, have been limited," he continued.

Zakashansky recalled that when the earlier PFS data from SOLO2 were presented, "questions were raised regarding the clinical uncertainty of the benefit associated with olaparib maintenance, primarily whether the PFS benefit...would translate to a long-term overall survival benefit."

For him, the current results "answer that question" and offer the "largest improvement in overall survival of any recurrent ovarian cancer patient trial reported to date."

Schilsky added that the new data confirm that olaparib "should be the standard maintenance therapy for patients with BRCA-related relapsed ovarian cancer responding to platinum-based chemotherapy."

The drug is already approved for this indication, but the new data showing a significant survival benefit are "comforting" and "good news," he said.

Adverse Events With Olaparib

Treatment-emergent adverse events seen in the study were "consistent with the known tolerability profile of olaparib," Poveda commented.

The most common events of any grade were nausea, fatigue/asthenia, and anemia. The most common event of grade ≥3 was anemia.

Adverse events leading to dose interruptions occurred in 50% of patients who received olaparib and 19% of patients who took placebo. Adverse events leading to dose reductions occurred in 28% and 3%, respectively.

Treatment discontinuation due to adverse events was reported in 17% of patients given olaparib and 3% of those in the placebo arm.

The study was funded by AstraZeneca and Merck Sharp & Dohme Corp. Poveda reports a consulting or advisory role with AstraZeneca, Clovis Oncology, PharmaMar, Roche, and Tesaro and receiving expenses from PharmaMar. Many coauthors also report relationships with pharmaceutical companies. 

American Society of Clinical Oncology (ASCO) 2019 Annual Meeting: Abstract 6002.

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

ASCO 2020-BENEFIT OF DEBULKING FOR RELAPSED OVARIAN CANCER

DESKTOP III became the first phase III, prospective, randomized trial to show an association between improved overall survival (OS) and secondary cytoreductive surgery in women with platinum-sensitive recurrent ovarian cancer (PSROC), offering hope for people with a condition that results in nearly 14,000 deaths annually. Data were presented during the ASCO20 Virtual Scientific Program (Abstract 6000) by lead study author Andreas du Bois, MD, PhD, of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) and Evangelische Kliniken Essen-Mitte, Germany.

Secondary cytoreductive surgery is a widely used yet under-researched treatment approach in managing PSROC. Prospective, randomized trials have been lacking in this area but could help clarify the role and outcomes of debulking as well as identify appropriate patients for cytoreduction.

Dr. Robert L. Coleman

As such, the AGO DESKTOP I and II trials informed the development of selection criteria to predict optimal candidates for debulking in PSROC.^1,2 The multicenter, international DESKTOP III trial (NCT01166737) then prospectively examined OS, progression-free survival (PFS), resection rate, and morality associated with the selection criteria developed in DESKTOP I and affirmed in DESKTOP II. Selection criteria included the AGO score based on an ECOG Performance Status score of 0, complete resection during first-line therapy, and ascites of < 500 mL.

In DESKTOP III, 407 patients with a platinum-free interval of more than 6 months and a positive AGO score were randomly assigned to either cytoreductive surgery with maximal effort toward complete resection (206 patients) or no surgery (201 patients).

“I am really happy to show a highly significant positive result of this trial,” Dr. du Bois said. “The median OS in the surgery arm was 53.7 months compared to 46 months in the no-surgery arm. This translates into a risk reduction of 25%, which was highly statistically significant. And the median OS gain between both arms was 8 months.”

“I am really happy to show a highly significant positive result of this trial,” Dr. du Bois said.

Dr. du Bois reported similar positive findings in PFS, which indicated a risk reduction of 34% and a median survival of 18.4 months in the surgery arm compared with 14.0 months in the no-surgery arm (HR 0.66, 95% CI [0.54, 0.82]; p < 0.001).

Positive outcomes in both endpoints appear largely due to the subgroup of surgical patients without residual disease.

“There was a huge impact of complete resection, which was achieved in [approximately] 75% of patients and ended up in a median OS exceeding 5 years after diagnosis of recurrent ovarian cancer, compared to only 28.8 months in those who ended surgery with residual disease,” Dr. du Bois said. “That translates into a risk reduction of 60%.”

Discussant Robert L. Coleman, MD, of US Oncology Research, noted that, compared with other similar secondary cytoreductive surgery trials such as SOC-1 (NCT01611766), debulking consistently appeared to have a favorable impact on mortality. Although only DESKTOP III met its primary endpoint of improving OS, both DESKTOP and SOC-1 demonstrated an added benefit of PFS.

“Both [trials] tout that the use of the triage algorithm to select patients for surgery can lead to complete gross resection in nearly three-quarters of patients; however, the price paid for being wrong is substantial, with no benefit seen in PFS and possibly a detriment in OS,” he added.

Interestingly, survival benefits of surgery were not observed in the GOG-213 trial, in which patients in both the treatment and control arms demonstrated remarkably similar median OS (Figure) and PFS results.³

Figure. Survival Comparisons in Three Trials of Platinum-Sensitive Recurrent Ovarian CancerAbbreviations: HR, hazard ratio; mos, months; CI, confidence interval; OS, overall survival.View larger

“It is clear that the detrimental effects of the failed surgical attempt must be considered in patient selection. Better biological understanding of tumor microenvironment also will help to better position all modalities of therapy into the current setting,” Dr. Coleman said. “Formal analytics among these three trials is warranted and is planned to better elucidate potential subgroups of surgical merit.”

– Emily A. Kuhl, PhD

ASCO 2020-SURVIVAL BENEFIT WITH OLAPARIB MAINTENANCE IN BRCA+ OVARIAN CANCER

The SOLO2 trial found olaparib maintenance therapy may have clinically relevant effects on overall survival (OS) in women with platinum-sensitive relapsed ovarian cancer (PSROC) with BRCA1/2 mutations (Abstract 6002). Andrés Poveda, MD, of Initia Oncology, Hospital Quirónsalud and GEICO, Spain, presented survival and safety outcomes from the trial during the ASCO20 Virtual Scientific Program.

“Recurrent ovarian cancer remains incurable to the majority of women, and therefore, extending OS is of great importance,” said Discussant Susana Banerjee, MBBS, MA, PhD, FRCP, of The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, United Kingdom. “Improvements in progression-free survival, time to subsequent therapy, and response are clinically meaningful and important trial endpoints. The introduction of PARP inhibitors has really changed the landscape of ovarian cancer.”

“The introduction of PARP inhibitors has really changed the landscape of ovarian cancer.” – Dr. Andrés Poveda

Despite advances in the management of ovarian cancer, such as the advent of the PARP inhibitor olaparib, OS remains an elusive target of studies that seek to mitigate relapsing disease.

SOLO2 is an international, randomized phase III trial to examine olaparib maintenance treatment in women with PSROC with BRCA1/2 mutations who have received at least two lines of previous platinum-based chemotherapy. Patients were randomly assigned to olaparib 300 mg bid (196 patients) or placebo (99 patients) until disease progression. Time-dependent endpoints presented at the program included OS, time to first subsequent therapy, duration of treatment exposure, and safety and toxicity profiles.

OS failed to reach statistical significance (HR 0.74, p = 0.0537) but nonetheless represents a clinically meaningful outcome, Dr. Poveda said.

“[In] the final analysis on OS, the median OS improved by 12.9 months with maintenance olaparib over placebo,” he said. “This is an impressive finding, particularly considering that 38% of [patients receiving] placebo crossed over to receive PARP inhibitor therapy.”

Time to first subsequent therapy was significantly better among patients in the treatment arm than those in the control arm (median 27.4 vs. 7.2 months, HR 0.37; p < 0.0001). At 5 years, 42% of patients on olaparib were alive and had not received subsequent treatment, compared with 33% of patients on placebo.

Mean duration of treatment exposure was 29.1 versus 13.1 months for placebo. Tolerability was acceptable, with 22% of patients in the treatment arm remaining on maintenance olaparib after at least 5 years. Only a small number of treatment-emergent adverse effects, dose modifications, and treatment discontinuations occurred among patients receiving olaparib over long-term treatment. Toxicities of particular interest included the emergence of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

“Perhaps the most important point here is the increased incidence in MDS and AML in both the olaparib arm at 8% and the placebo arm at 4%,” Dr. Banerjee said. “However of note, in the SOLO1 trial, where patients received first-line treatment for around 2 years, the incidence of MDS and AML was much lower—1% versus 0% in the placebo arm.”¹

Dr. Banerjee also emphasized that although OS in SOLO2 was clinically relevant, and it was “reassuring” to see that more than 1 in 5 patients remained on maintenance therapy for at least 5 years, unanswered questions about olaparib remain and should inform future studies.

“In the current era of first-line PARP inhibitor maintenance therapy, how relevant are these results and other recurrent trials, including the population of patients [who] are naive to PARP inhibitors?” she asked. “The reality is, there will remain a substantial proportion of women who would not have had PARP inhibitors in the first-line setting but then go on to relapse, and therefore this [question] is applicable.”

Dr. Banerjee also noted that there may be situations where a PARP inhibitor is reserved for recurrent disease in women with hormone receptor–proficient tumors.

“What about OS in patients without a BRCA mutation?” she asked. “We need to wait for [data from] NOVA and ARIEL3.”

— Emily A. Kuhl, PhD

ASCO 2020-NO BENEFIT OF ADDING CEDIRANIB TO OLAPARIB IN OVARIAN CANCER

Results of the NRG Oncology phase III clinical trial NRG-GY004 indicated that the addition of the investigational agent cediranib to olaparib and standard platinum-based chemotherapy did not improve progression-free survival outcomes for women with platinum-sensitive ovarian cancer; however, activity between the treatments was similar in patients. These results were recently presented by Joyce F. Liu, MD, and colleagues during the ASCO20 Virtual Scientific Program (Abstract 6003).

Joyce F. Liu, MD

Study Background and Methodology

NRG-GY004 was designed to expand upon the findings of a phase II trial that indicated a combination of cediranib and olaparib improved progression-free survival outcomes compared to olaparib alone for women with platinum-sensitive, high-grade serous/endometrioid ovarian cancer, regardless if they had a BRCA mutation.

In NRG-GY004, women were randomly assigned to one of three treatment regimens. Participants randomly assigned to the first treatment arm received standard-of-care chemotherapy with either carboplatin and paclitaxel, carboplatin and gemcitabine, or carboplatin and pegylated lipsomal doxorubicin. The participants on the experimental treatment arms either received olaparib at 300 mg twice a day or olaparib at 200 mg twice a day with cediranib at 30 mg twice a day. The primary endpoint of this study was to assess the progression-free survival benefit of cediranib and olaparib treatment compared to chemotherapy for women with platinum-sensitive ovarian cancer.

Between March 2016 and June 2018, 565 patients had enrolled in NRG-GY004 and, of those patients, 528 initiated treatment; 23.7% of the patients had a germline BRCA mutation.

Results

At a median follow-up of 29.1 months, the hazard ratio for progression-free survival was 0.856 (95% confidence interval [CI] = 0.66–1.11, P = .08, 1-tail) for the combination of cediranib and olaparib compared to chemotherapy treatment. The hazard ratio for progression-free survival was 1.20 (95% CI = 0.93–1.54) for olaparib alone compared to chemotherapy treatment. Median progression-free survival for patients was 10.3 months for the standard of care, chemotherapy; 8.2 months for olaparib alone; and 10.4 months for patients receiving cediranib plus olaparib. In a predefined biomarker subset analysis of women with a germline BRCA mutation, the progression-free survival hazard ratio was 0.55 (95% CI = 0.73–1.30) for combined cediranib and olaparib compared to chemotherapy and 0.63 (95% CI = 0.37–1.07) for olaparib alone vs standard chemotherapy. In women without a germline BRCA mutation, the progression-free survival hazard ratio was 0.97 (95% CI = 0.73–1.30) for cediranib plus olaparib compared to chemotherapy and 1.41 (95% CI = 1.07–1.86) for olaparib alone vs standard chemotherapy.

"While the combination of cediranib and olaparib was not found to improve progression-free survival compared to [the] standard-of-care chemotherapy, the findings of this study suggest that non–platinum-based alternatives have potential in this setting, especially in appropriate biomarker subgroups such as patients with BRCA mutations."
Tweet this quote

“This is the first phase III trial comparing a completely oral non–platinum-based therapy regimen to standard of care platinum-based chemotherapy in platinum-sensitive ovarian cancer. While the combination of cediranib and olaparib was not found to improve progression-free survival compared to [the] standard-of-care chemotherapy, the findings of this study suggest that non–platinum-based alternatives have potential in this setting, especially in appropriate biomarker subgroups such as patients with BRCA mutations,” stated Dr. Liu, of the Dana-Farber Cancer Institute.

There were no overall survival differences between the treatment arms. Patients who received cediranib and olaparib in addition to the standard of care did experience a higher frequency of grade 3 or higher gastrointestinal, hypertension, and fatigue adverse events.

Disclosure: 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®.

---

CARBOPLATIN-CAELYX BETTER THAN CARBOPLATIN-GEMCITABINE FOR OVARIAAN CANCER

 Carboplatin-pegylated liposomal doxorubicin-bevacizumab is the new standard of care for women with recurrent ovarian cancer sensitive to treatment with platinum-based and antiangiogenic treatment, researchers say.

"This is the first phase-3 study comparing two bevacizumab-containing regimens in recurrent ovarian cancer," Dr. Jacobus Pfisterer of the Gynecologic Oncology Center in Kiel, Germany, told Reuters Health by email. "The experimental arm did better than the current standard of care with respect to progression-free survival and overall survival, with no new toxicities."

German national guidelines were changed to incorporate the study results, he noted. "The experimental arm is the new standard of care. The next step is a phase-3 study adding immunotherapy" to this regimen, he said.

The multicenter open-label trial involved 682 patients (median age, about 63) randomized to receive carboplatin-pegylated liposomal doxorubicin-bevacizumab (experimental group) or carboplatin-gemcitabine-bevacizumab (standard group).

The experimental group received six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (area under the concentration curve 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m2, day 1) every four weeks.

The standard group received six cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (AUC 4, day 1) plus gemcitabine (1000 mg/m2, days 1 and 8) every three weeks.

Both regimens were followed by maintenance bevacizumab (15 mg/kg every three weeks until disease progression or unacceptable toxicity).

As reported in The Lancet Oncology, median progression-free survival was 13.3 months in the experimental group versus 11.6 months in the standard group (hazard ratio, 0.81).

Median overall survival, a secondary endpoint, was 31.9 months in the experimental group versus 27.8 months in the standard group (HR 0.81).

Eighty-four patients (11%, experimental group vs.14%, standard) received post-progression bevacizumab for a median duration of 20.5 days (both groups).

Almost all patients had at least one adverse event during the study (98% vs. 97%).

The most common grade 3 or 4 adverse events were hypertension (27%, experimental vs. 20%, standard) and neutropenia (12% vs. 22%). Serious adverse events occurred in 10% of experimental group patients and 9% of those in the standard group.

One treatment-related death occurred in the experimental group (large intestine perforation) and two in the standard group (one case each of osmotic demyelination syndrome and intracranial hemorrhage).

The authors conclude, "Carboplatin-pegylated liposomal doxorubicin-bevacizumab is a new standard treatment option for platinum-eligible recurrent ovarian cancer."

Dr. Richard Penson of Massachusetts General Hospital in Boston, author of a related editorial, commented by email to Reuters Health, "The unexpected result was that carboplatin, pegylated liposomal doxorubicin, and bevacizumab (CD-BEV) improved overall survival by four months, with significant improvements in quality of life, meeting all the criteria for a new standard of care."

"Establishing 'optimal' chemotherapy is a complicated trade-off between being toxic to the cancer and kind to the patient," he said. "CD-BEV may have that balance just right, though guidelines tend to reflect clinicians' wish to maximize the number of options, rather than ranking them."

"The greatest benefit to the regimen is that it potentially gets the greatest good for the greatest number, by delivering the best chance of remission that can consolidated by the use of a PARP inhibitor, and it is this 'switch maintenance' that offers the hope for the most durable control of a dreadful disease," he concluded.

The study was funded by F Hoffmann-LaRoche. Dr. Pfisterer and numerous coauthors have received fees from the company.

SOURCE: https://bit.ly/2VIP8uD and https://bit.ly/2KAsQES The Lancet Oncology, online April 16, 2020.

NO BENEFIT OF SECONDARY CYTOREDUCTION FOR OVARIAN CANCER

In a recent issue of The New England Journal of Medicine, Coleman et al released the results from the GOG-0213 trial, a multicenter, randomized prospective trial that compared secondary cytoreduction followed by chemotherapy with chemotherapy alone in women with platinum-sensitive recurrent ovarian cancer.¹ Ovarian cancer is a devastating diagnosis, with more than 22,000 new cases diagnosed each year and more than 14,000 deaths annually. Even if the cancer is initially controlled, more than 80% of patients eventually have recurrence.Not surprisingly, promising treatments for recurrent ovarian cancer are under active investigation. A number of studies have supported the application of secondary cytoreduction for resectable recurrent disease, and the National Comprehensive Cancer Network Guidelines Clinical Practice Guidelines in Oncology: Ovarian Cancer lists surgery as an option for patients who have relapsed more than 6 months after complete response to prior chemotherapy.

Closer Look at GOG-0213

In the current trial, reviewed in this issue of The ASCO Post, 485 patients with recurrent ovarian cancer who were historically considered candidates for secondary cytoreduction (one prior therapy, platinum-free interval of more than 6 months, small volume of recurrent disease, investigator-determined resectable disease) were randomly assigned to receive secondary cytoreduction followed by chemotherapy vs chemotherapy alone. Overall, 67% of the patients in the surgery arm achieved complete gross resection. All patients received platinum-based chemotherapy of the treating physician’s choice (carboplatin/paclitaxel or carboplatin/gemcitabine); 84% of the patients also received bevacizumab with chemotherapy and as maintenance, and this was equally distributed between the two groups.

At a median of 48.1 months of follow-up, the median overall survival was statistically similar at 50.6 months for those undergoing surgery plus chemotherapy compared with 64.7 months for those undergoing chemotherapy alone (P = .08). The median progression-free survival was also similar. However, among those patients not receiving bevacizumab, surgical patients demonstrated significantly poorer survival than did those receiving chemotherapy alone (hazard ratio = 2.26, 95% confidence interval = 1.3–3.88). Although no significant difference was noted in overall survival between those undergoing complete surgical resection vs chemotherapy alone, there was a significant advantage to surgery in terms of progression-free survival. As expected, patients undergoing complete cytoreduction had improved overall and progression free survival compared with those who had residual disease.

Dr. Ray is a gynecologic oncology fellow at Fox Chase/Temple University Hospital, Philadelphia. Dr. Chu is Professor, Department of Surgical Oncology, and Director, Gynecologic Oncology Fellowship Program, Fox Chase/Temple University Hospital, Philadelphia.

Who May Benefit From Secondary Surgery?

A number of prior studies have focused at identifying candidates who will benefit from secondary cytoreductive surgery. Patients with a prolonged platinum-free interval (> 6 months) and those with an isolated or limited volume of disease (< 0.5 cm) at recurrence have the greatest benefit from secondary surgery compared with those with a shorter progression-free interval or abundant disease.^2-4 In a pooled analysis of 1,100 patients in 2011,⁴ Zang et al showed a median survival of 57.6 months after complete secondary cytoreductive surgery, compared with 27.0 months in those with residual disease of 0.1 to 1 cm and 15.6 months in those with residual disease of more than 1 cm, respectively (P < .0001). Even after selecting for a group of patients with favorable characteristics, GOG-0213 found no improvement in survival with the addition of surgery to chemotherapy.

But do these findings realistically apply to our patient populations? The GOG-0213 trial was a well-designed, open-label phase III multicenter international randomized clinical trial with more than 50% of the patients enrolled in the United States. The randomization also accounted for prior length of progression-free interval and type of second-line chemotherapy. The authors did acknowledge that the median overall survival was nearly three times longer than expected, based on previous studies. They suggested that the improved overall survival is a reflection of advances in clinical care and more effective treatment options in current use.

In addition, as previously noted, this trial had narrow selection criteria, including only those patients with the most favorable prognostic indicators: small volume, easily resectable, chemotherapy-sensitive disease, with a median 20-month progression-free survival interval. The findings therefore may not be as applicable to patients with shorter progression-free survival intervals or a larger disease burden at presentation, who make up a large portion of the patients with recurrent ovarian cancer. Although patients may be willing to accept higher risks of complications in exchange for improvement in overall survival,⁵ the current study demonstrates no improvement in survival for patients undergoing surgery compared with chemotherapy alone.

Of note, this trial did allow for the use of bevacizumab therapy in either group, a reflection of the evolution in current practice. Bevacizumab has a proven benefit in this select patient population with respect to both progression-free and overall survival⁶ and may account for the longer-than-anticipated duration of overall survival. Any benefits of cytoreductive surgery may be minimized in the current era, where biologic therapies (bevacizumab, poly [ADP-ribose] polymerase inhibitors, checkpoint inhibitors) are being incorporated into front-line, maintenance, and recurrent treatment regimens.

Ongoing Phase III Trials

The lack of benefit for the addition of surgery to chemotherapy in this patient population leaves open the question of whether there is a different patient population that would benefit from surgery. Three other phase III trials are being conducted to compare surgery with chemotherapy vs chemotherapy alone, with slight differences in patient selection or selected adjuvant therapy.

DESKTOP III uses a similar trial design as GOG-0213 but includes only patients who had complete gross resection at the time of primary surgery, which has been shown to be another indicator of successful secondary cytoreduction.⁷ In contrast to GOG-0213, with 84% bevacizumab use, only approximately 20% of patients in DESKTOP III were treated with bevacizumab (ClinicalTrials.gov number NCT01166737).

The SOC 1 trial (NCT01611766) being conducted in China will assess progression-free and overall survival as primary endpoints. In addition, its secondary outcome is to validate the iMODEL risk model of patient selection criteria in platinum-sensitive recurrent ovarian cancer. A third trial, SOCceR (Netherlands Trial Register number NL3137), is also underway.

Although there continues to be clear interest in investigating the utility of secondary cytoreduction in patients with recurrent ovarian cancer, evaluation of the data from all the upcoming prospective randomized trials will help determine which patients, if any, will benefit from secondary cytoreduction. It is possible that with the development of newer effective pharmaceutical options, secondary cytoreductive surgery may no longer have a major role in the treatment of recurrent ovarian cancer.