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Immunotherapy After Locally Ablative Therapy for Oligometastatic NSCLC

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Key Points

  • Median progression-free survival from the start of locally ablative therapy was significantly greater vs historical data.
  • Median progression-free survival from the start of pembrolizumab was 18.7 months.

In a single-center phase II trial reported in JAMA Oncology, Bauml et al found that pembrolizumab given after locally ablative therapy appeared to be associated with improved outcomes in patients with oligometastatic non­–small cell lung cancer (NSCLC).

In the study, 45 evaluable patients with four or fewer metastatic sites were treated between February 2015 and September 2017 at Abramson Cancer Center with pembrolizumab at 200 mg every 21 days for eight cycles. Treatment could continue for up to 16 cycles in the absence of progressive disease or unacceptable toxicity. Pembrolizumab treatment began within 4 to 12 weeks of completion of locally ablative therapy to all known disease sites.

The primary outcome measures were progression-free survival from the start of locally ablative therapy and progression-free survival from the start of pembrolizumab therapy. The study was powered for comparison with historical data for progression-free survival from the start of locally ablative therapy. Quality of life was assessed using the Functional Assessment of Cancer Therapy–Lung (FACT-L) instrument.

Progression-Free Survival

After a median follow-up of 23.2 months for surviving patients, the median progression-free survival from the start of locally ablative therapy was 19.1 months—significantly greater than a historical median of 6.6 months (P = .005). Median progression-free survival from the start of pembrolizumab therapy was 18.7 months.

Overall, 40% of patients completed 16 cycles of treatment. Estimated overall survival was 90.9% at 12 months and 77.5% at 24 months. No significant association was observed between progression-free survival from the start of locally ablative therapy and programmed cell death ligand 1 expression or CD8 T-cell tumor infiltration.

Adverse Events

The most common treatment-related adverse events of any grade during pembrolizumab treatment were pain (42%), fatigue (36%), and rash (22%). The most common grade 3 or 4 adverse event was pneumonitis (6%). Overall, pneumonitis of any grade occurred in five patients (11%). Grade 3 colitis occurred in two patients, and two patients had adrenal insufficiency (one grade 2 and one grade 3).

There was no significant change in median FACT-L total score between baseline and either cycle 8 or cycle 16 of pembrolizumab treatment.

The investigators concluded, “Pembrolizumab after [locally ablative therapy] for oligometastatic NSCLC appears to improve [progression-free survival], with no reduction in quality of life.”

Joshua M. Bauml, MD, of the Abramson Cancer Center, Perelman Center for Advanced Medicine, University of Pennsylvania, is the corresponding author for the JAMA Oncology article.

Disclosure: This study was supported by Merck & Co.  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®.


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