Effect of Previous Radiotherapy on Outcome With Pembrolizumab in NSCLC


Key Points

  • Pembrolizumab was associated with improved progression-free and overall survival in patients with advanced NSCLC who had received prior radiotherapy.
  • Pulmonary toxicity was increased in those who had received prior thoracic radiotherapy.

In a single-site experience reported in The Lancet Oncology by Shaverdian et al, patients with advanced non–small cell lung cancer (NSCLC) in the phase I KEYNOTE-001 trial of pembrolizumab (Keytruda) were found to have better outcomes if they had received prior radiotherapy.

Study Details

The analysis included 97 evaluable patients from the trial enrolled at the University of California Los Angeles. Of them, 42 patients (43%) had previously received any radiotherapy for NSCLC before the first cycle of pembrolizumab, including 38 (39%) receiving extracranial radiotherapy and 24 (25%) receiving thoracic radiotherapy. Median follow-up was 32.5 months.

Improved Outcomes

Median progression-free survival was 4.4 months in patients receiving any prior radiotherapy vs 2.1 months in those receiving no prior radiotherapy (hazard ratio [HR] = 0.56, P = .019) and 6.3 months vs 2.0 months in those receiving extracranial radiotherapy vs no extracranial radiotherapy (HR = 0.50, P = .0084). Median overall survival was 10.7 months vs 5.3 months for those with any prior radiotherapy vs no radiotherapy (HR = 0.58, P = .026) and 11.6 months vs 5.3 months for those with vs without prior extracranial radiotherapy (HR = 0.59, P = .034).

Pulmonary Toxicity

Pulmonary toxicity was observed in 15 of 24 patients (63%) with prior thoracic radiotherapy and in 29 of 73 patients (40%) with no prior thoracic radiotherapy, with toxicity considered related to treatment in 13% vs 1% (grade ≥ 3 in 1 patient in each group).

The investigators concluded: “Our data suggest that previous treatment with radiotherapy in patients with advanced NSCLC results in longer progression-free survival and overall survival with pembrolizumab treatment than that seen in patients who did not have previous radiotherapy, with an acceptable safety profile. Further clinical trials investigating this combination are needed to determine the optimal treatment strategy for patients with advanced NSCLC.”

The study was funded by the National Institutes of Health.

Percy Lee, MD, of the Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles, is the corresponding author of The Lancet Oncology article.

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