The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The addition of pembrolizumab to first-line etoposide and platinum significantly improved progression-free in patients with extensive-stage small cell lung cancer (SCLC), according to results of the KEYNOTE-604 presented at the ASCO20 Virtual Scientific Program.

This addition of pembrolizumab also appeared to prolong overall survival compared with etoposide and platinum alone, but the prespecified significance threshold was not met.

“In the past 2 years the IMPOWER 133 trial and the CASPIAN trial have demonstrated a significant survival advantage for the addition of anti–PD-L1 blockade with either atezolizumab or durvalumab in the context of first-line chemotherapy for small cell lung cancer,” said Charles M. Rudin, MD, of Memorial Sloan Kettering Cancer Center, who presented the results. “Taken together these data support the benefit of pembrolizumab in patients with SCLC and add to the growing body of evidence of immune checkpoint inhibitors in a historically difficult to treat cancer.”

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The study randomly assigned 453 previously untreated patients with no untreated central nervous system metastases to pembrolizumab 200 mg every 3 weeks or placebo up to 35 cycles plus 4 cycles standard-dose etoposide and platinum (investigator’s choice of carboplatin or cisplatin).

The coprimary endpoints were overall survival and progression-free survival in the intention-to-treat population.

The median age of patients was 65 years. Baseline brain metastases were present in 14% of the pembrolizumab group compared with 10% of the placebo group.

At the time of the final analysis, the median follow-up of 21.6 months, 9% of patients in the pembrolizumab arm and 1% in the placebo arm remained on treatment. A similar percentage of patients underwent prophylactic cranial irradiation.

At the time of the second interim analysis — the final analysis for progression-free survival — with a median follow-up of 13.5 months, pembrolizumab significantly improved progression-free survival (hazard ratio [HR], 0.75; 95% CI, 0.61-0.91; P =.0023). The median progression-free survival was 4.5 months compared with 4.3 months for placebo.

Updated PFS curves at the time of final analysis showed a long-term benefit of pembrolizumab in a subset of patients. The 1-year progression-free survival improved from just 5% with etoposide to 15% with the addition of pembrolizumab, Dr Rubin said. This benefit appear to be maintained over time.

By the final analysis, pembrolizumab plus etoposide and platinum prolonged overall survival, but the significance threshold was not met (HR, 0.80; 95% CI, 0.64-0.98; P =.0164). This narrowly missed the superiority threshold of P =0.0128. The median overall survival was 10.8 months compared with 9.7 months.

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In an exploratory analysis of as-treated patients, the overall survival did meet this superiority threshold, with a hazard ratio of 0.78 and a P value of 0.0124. This further supports the clinical benefit of adding pembrolizumab to etoposide and platinum, Dr Rubin said.

According to Dr Rudin, the observed adverse events were as expected with these drugs. About 77% and 75% of patients assigned to pembrolizumab or placebo experienced grade 3/4 adverse events, respectively. Fifteen percent of patients assigned to receive pembrolizumab discontinued treatment because of adverse events compared with 6% of patients assigned to the placebo arm.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.


Rudin CM, Awad MM, Navarro A, et al. KEYNOTE-604: Pembrolizumab (pembro) or placebo plus etoposide and platinum (EP) as first-line therapy for extensive-stage (ES) small-cell lung cancer (SCLC). Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 9001.