AGGRESSIVE TREATMENT FOR PATIENTS WITH OLIGOMETASTATIC NSCLC

Patients with oligometastatic stage IV nonsmall cell lung cancer (NSCLC) can significantly benefit from the addition of radiation therapy or surgery after standard systemic therapy, according to new findings.

Those who received radiation/surgery experienced a median overall survival rate of 41.2 months versus 17.0 months for patients who received standard maintenance therapy/observation (MT/O) (P = .017).

Progression-free survival, which was the study's primary outcome, was 14.2 months for those in the combination group, compared with 4.4 months for those who received standard MT/O (P = .014).

"With long-term follow-up, lung consolidative therapy (LCT) in patients with oligometastatic disease who do not progress after frontline systemic therapy have improved progression free survival," said lead author Daniel Gomez, MD, associate medical director of radiation oncology at the University of Texas MD Anderson Cancer Center in Houston. "It is also associated with an improvement in overall survival."

Gomez presented his findings at the American Society for Radiation Oncology (ASTRO) 2018 Annual Meeting.

Gomez and his team previously reported that LCT can improve progression-free survival in patients with oligometastatic NSCLC after they have completed frontline systemic therapy without progression. The interim results, which also included toxicity data, were for a median follow-up of 12.4 months.

In that earlier trial, progression-free survival was significantly superior in the LCT cohort compared with the control group (median 11.9 vs 3.9 months; hazard ratio, 0.35; log-rank P = .0054), which led to the early termination of the trial by the data and safety monitoring board. An analysis of time to new site of metastatic disease was also significantly longer in the LCT group compared with those who received maintenance systemic therapy or observation only (median 11.9 vs 5.7 months; P = .0497). However, because of the short-term follow-up, overall survival data were not mature enough to be reported.

These new results include updated data on progression-free survival as well as overall survival and toxicity data for 38.8 months of patient follow-up (range, 28.3-61.4 months).

Overall Survival Improved

The study included 49 patients (enrollment was stopped because of the trial's early termination) from three institutions who had not experienced progression after standard frontline systemic therapy. Frontline therapy included four or more cycles of platinum doublet therapy or 3 or more months of EGFR or ALK inhibitors for patients with EGFR mutations/ALK rearrangements, respectively. All patients had stage IV NSCLC with three or fewer metastatic lesions, and the cohort was randomized to MT/O or LCT, defined as radiation or surgery to all remaining active sites of disease.  

The primary endpoint was progression-free survival and secondary endpoints included overall survival, toxicity, and time to appearance of a new lesion.Time to new lesion failure trended towards significance with a median of 14.2 months in the LCT group compared with 6.0 months in the MT/O group (P = .11).

Gomez also noted that crossover was permitted in this trial. "If you progressed on standard therapy, you could then crossover to the other group," he said. "The question then becomes: Does early LCT offer similar survival outcomes as late LCT after progression?"

They found that the median survival after progression was significantly higher in the LCT group versus the MT/O group; 37.6 months compared with 9.4 months (P = .034).

"Patients that received complete LCT at the time of progression—in either group—can offset any detriment in overall survival to some extent by receiving aggressive therapy," Gomez said.

A limitation of this study is that it was conducted prior to the advent of immunotherapy in lung cancer. "That has transformed the paradigm of treatment in many settings, including stage IV disease," he explained.

Breakthrough for Patient Care

Commenting on the study, Kenneth Rosenzweig, MD, system chair and professor of radiation oncology at the Mount Sinai Health System in New York, noted that this update on a "previously reported groundbreaking study further confirms the importance of treating discrete metastatic lesion in patients with stage IV NSCLC."

  Previously if a patient had any metastatic disease, the only accepted treatment was systemic therapy.    Kenneth Rosenzweig, MD 

This study along with similar studies that have subsequently been reported represent a paradigm shift in the way this disease is treated. "Previously if a patient had any metastatic disease, the only accepted treatment was systemic therapy, such as chemotherapy or targeted therapies," said Rosenzweig, noting that surgery or radiation was only used if lesions were causing symptoms.

"With this update, we now know eliminating sites of disease with ablative techniques such as stereotactic radiation improves survival," he added. "This is an enormous breakthrough for patient care, and Gomez and his co-investigators are to be commended for their foresight and diligence in completing this trial."

Another expert also weighed in on the results. "For a long time, we never really imagined that we could cure stage IV disease, but there are many paradigms that are emerging where we are seeing an increasing relevance for local regional treatment," said Katherine Park, MD, a radiation oncologist from the University of California, San Francisco.

With the advent of improved therapies that can eradicate distant disease very effectively, there seems to be a great opportunity for radiation therapy to treat remaining localized disease, she noted. 

"I think we will see this theme more and more as we look at other sites in terms of treating oligometastasis," said Park, who is an ASTRO expert. "There are multiple opportunities to see how radiation therapy can impact a systemic disease."

This study was jointly funded by the MD Anderson Lung Cancer Priority Fund, MD Anderson Cancer Center Moon Shot Initiative, Cancer Center Support (Core), National Cancer Institute, and National Institutes of Health. Rosenzweig has reported no relevant financial relationships. Gomez has reported relationships with Merck, Varian, Elekta, Driver Oncology, US Oncology, Bristol-Myers Squib, AstraZeneca, and RefleXion.

Annual Meeting of the American Society for Radiation Oncology (ASTRO) 2018. Abstract LBA 3. Presented October 21, 2018.

For more news, join us on Facebook and Twitter