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Concurrent Pembrolizumab and Chemoradiotherapy in Locally Advanced NSCLC


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In a phase I trial reported in JAMA Oncology, Jabbour et al found that the use of pembrolizumab concurrently with chemoradiotherapy in advanced non–small cell lung cancer (NSCLC) was tolerable, and that progression-free survival with the combination therapy was 69.7% at 12 months.

As stated by the investigators, “Consolidative programmed cell death ligand 1 (PD-L1) inhibition after chemoradiotherapy improves overall survival and progression-free survival for stage III NSCLC and requires safety evaluation for incorporation of programmed cell death 1 (PD-1) inhibition at the onset of chemoradiotherapy.”

Study Details

In the study, a total of 21 patients with unresectable stage III disease received pembrolizumab with chemoradiotherapy (weekly carboplatin and paclitaxel with 60 Gy of radiation in fractions of 2 Gy per day) in five cohorts:

  • Pembrolizumab at 200 mg every 3 weeks (full dose) 2 to 6 weeks after chemoradiotherapy (cohort 1)
  • Pembrolizumab at 100 mg every 3 weeks (reduced dose) starting on day 29 of chemoradiotherapy (cohort 2)
  • Full-dose pembrolizumab starting on day 29 of chemoradiotherapy (cohort 3)
  • Reduced-dose pembrolizumab starting on day 1 of chemoradiotherapy (cohort 4)
  • Full-dose pembrolizumab starting on day 1 of chemoradiotherapy (cohort 5).

Dose-limiting toxicity was defined as pneumonitis of at least grade 4 within cycle 1 of pembrolizumab treatment.

Toxicity

No dose-limiting toxicity was observed in any cohort. One patient in a safety expansion cohort developed grade 5 pneumonitis while receiving the cohort 5 regimen. One patient had grade 3 pneumonitis. In addition to pneumonitis (10%), the most common grade ≥ 3 adverse events were lymphopenia (24%), dyspnea (10%), and neutropenia (10%). Immune-related grade ≥ 3 adverse events occurred in four patients (18%).

KEY POINTS

  • One patient in a safety expansion cohort developed grade 5 pneumonitis.
  • Among all patients, median progression-free survival was 18.7 months, with 6- and 12-month rates of 81.0% and 69.7%.

Progression-Free Survival

Among all 21 patients receiving at least one dose of pembrolizumab, median progression-free survival was 18.7 months, with 6- and 12-month rates of 81.0% and 69.7%. Among 19 patients receiving at least two doses of pembrolizumab, partial response was observed in 14 (74%), complete response in 3 (16%), and stable disease in 1 (5%); median progression-free survival among these patients was 21.0 months, with 6- and 12-month rates of 84.2% and 78.2%. No association between PD-L1 status and progression-free survival was observed.

The investigators concluded, “These findings suggest that combined treatment with PD-1 inhibitors and chemoradiotherapy for stage III NSCLC is tolerable, with promising [progression-free survival] of 69.7% at 12 months, and requires further study.”

Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey, Rutgers University, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded 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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