1. May, Brandon

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In patients with non-small cell lung cancer (NSCLC), around 7 percent of cases present with a limited number of metastatic foci (Lung Cancer 2013;82(2):197-203). Locally ablative therapy (LAT) directed to all sites of disease may improve survival endpoints, yet little is known regarding whether the addition of another therapeutic regimen may further benefit patients with NSCLC.

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Immunotherapy, a promising option for cancer care, may be one such additional approach to LAT in the treatment of NSCLC. Active research is being conducted in the combination of pembrolizumab, as well as other immunotherapies, with ablative treatments.


Researchers from Penn Medicine's Abramson Cancer Center have found that the addition of immunotherapy following LAT improves progression-free survival (PFS) and does not negatively impact quality of life in patients with oligometastatic NSCLC. Specifically, the university researchers found that the administration of pembrolizumab following LAT to all sites of disease was associated with an almost tripled median PFS compared with the historical mean.


While chemotherapy represents the standard treatment for NSCLC, recent evidence points to a greater number of options for patients with limited metastatic disease.


"Historically, patients with oligometastatic disease, or those with a limited burden of metastatic disease, were treated with systemic therapy only with palliative intent," lead study author Joshua M. Bauml, MD, Assistant Professor of Hematology-Oncology in Penn's Perelman School of Medicine, told Oncology Times. "In colon cancer, however, we know that patients with metastatic disease limited to the liver can be cured with hepatic resection. There have now been multiple trials showing improved outcomes for patients with oligometastatic lung cancer treated with locally ablative therapy, where we use definitive treatment approaches to eradicate all known disease."


These trials, he added, have led many clinicians to consider such an approach. "Our trial added in immunotherapy after LAT," Bauml said. "Immunotherapy using PD-1 blockade has already become standard of care in metastatic NSCLC, but its role in oligometastatic disease was heretofore unknown."


Study Details

The findings from this study build on previous research that demonstrates a survival and PFS benefit associated with pembrolizumab in patients with NSCLC (JAMA Oncol 2019; doi: 10.1001/jamaoncol.2019.1449). In the single-arm, phase II trial, a total of 51 patients with oligometastatic NSCLC who had completed LAT to all sites of disease were enrolled.


Researchers at Penn Abramson Cancer Center wrote that they had hoped to perform subgroup analyses on the outcomes in patients who received and did not receive radiotherapy. The small number of patients who were radiotherapy-naive, however, precluded the ability of the researchers to perform these analyses at this stage.


Pembrolizumab was administered intravenously at 200 mg every 21 days for 8 cycles within 4-12 weeks of finishing LAT. In the absence of progressive disease or untoward toxic effects, patients continued immunotherapy to 16 cycles.


The small study included 45 patients who received the immunotherapy, of whom 24 had either progressive disease or had died. There was a significantly greater median PFS from the start of LAT compared at 19.1 months compared with the historical median of 6.6 months (p=0.005). The median PFS from the start of pembrolizumab was 18.7 months. A total of 11 patients died during the study. At 12 months, the overall mean survival was 90.9 percent, whereas the mean survival rate at 24 months was 77.5 percent.


Although the researchers were unable to find any clinical variables associated with clinical outcomes, the findings did suggest improved PFS from the start of LAT in patients with metachronous disease versus patients with synchronous disease at 24 months. Similar findings were observed for patients with tumors positive for PD-L1 versus patients with tumors negative for PD-L1.


No new safety signals associated with pembrolizumab were reported. Approximately 11 percent of patients experienced pneumonitis, and 100 percent of these patients had received prior thoracic radiotherapy.


Currently, Bauml noted that it would be interesting to see if the study's findings could be replicated in immunotherapies other than pembrolizumab. In terms of the study's limitations, it was a single-center, single-arm study that included a relatively small sample size.


"We compared PFS to a historical control, which is difficult as historical reference populations in oligometastatic disease can be heterogeneous," he commented. "We believe it is essential that these findings be confirmed in a randomized controlled trial, and we are working on designing such a study."


Brandon May is a contributing writer.


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