Pembrolizumab-based regimen continues to show favourable signals for ES-SCLC

In the long-term follow-up of the KEYNOTE-604 study, the combination regimen comprising pembrolizumab and etoposide/platinum (EP*) continued to demonstrate survival benefit as first-line therapy for patients with previously untreated extensive-stage small cell lung cancer (ES-SCLC).

“To build on [our earlier findings,] we present updated results after a median 3.5 years of follow-up and … in patients who completed a maximum of 35 cycles of pembrolizumab on study,” said Dr Charles Rudin from Memorial Sloan Kettering Cancer Center, New York City, New York, US, at WCLC 2022.

KEYNOTE-604 included 453 participants (median age 64 years, 65 percent male) who were randomized 1:1 to receive either pembrolizumab 200 mg or placebo (day 1), plus four cycles of standard-dose EP Q3W. [WCLC 2022, abstract 1849]

 

Long-term survival benefit

Pembrolizumab-EP trumped the placebo-EP combo in terms of overall survival (OS; median 10.8 vs 9.7 months; hazard ratio [HR], 0.76), with a 3-year OS rate that was almost threefold higher (15.5 percent vs 5.9 percent). “[The] OS benefit with pembrolizumab-EP was observed despite ~15 percent of patients on placebo-EP receiving subsequent immune checkpoint inhibitors,” noted Rudin.

A similar trend favouring the pembrolizumab-based over the placebo-based regimen was seen in terms of progression-free survival (PFS; median 4.8 vs 4.3 months; HR, 0.70). PFS rate at 3 years was also higher with pembrolizumab-EP vs placebo-EP (6.9 percent vs 0.5 percent).

Both OS and PFS remained better with pembrolizumab-EP than placebo-EP across most** subgroups, except for patients who had brain metastasis at baseline.

These benefits augment the OS (HR, 0.80; p=0.0164) and PFS results (HR, 0.75; p=0.0023) that have been previously reported. [J Clin Oncol 2020;38:2369-2379]

 

Responses, AEs

Compared with the placebo-EP arm, the pembrolizumab-EP arm had a higher overall response rate (ORR; 70.6 percent vs 61.8 percent) and longer median duration of response (DoR; 4.2 vs 3.7 months). Best overall response was primarily driven by the higher rate of partial response (PR) in the pembrolizumab-EP vs the placebo-EP arm (68.4 percent vs 60.9 percent).

The rate of all-cause adverse events (AEs) leading to discontinuation of any treatment was nearly thrice as high with pembrolizumab-EP vs placebo-EP (15.7 percent vs 6.3 percent), but there were similar incidences of grade 3–5 AEs between arms (78.9 percent vs 77.1 percent).

There were no new AEs leading to death since the previous data cutoff. One patient in the placebo-EP arm died owing to an immune-mediated AE (pneumonitis), as opposed to none in the pembrolizumab-EP arm.

 

After 35 pembrolizumab cycles

Of the 18 patients who completed 35 cycles of pembrolizumab, 14 were alive as of the last evaluation prior to data cutoff. In the placebo-EP arm, only two completed 35 cycles and were alive as of data cutoff.

ORR was 100 percent, while median DoR was not reached. Sixteen patients had a PR while two had a complete response. At about 2 years (time of completion of the 35 cycles), median OS was not reached, and 2-year OS rate was 72 percent.

 

Meaningful improvement, durable responses

“[In this updated analysis,] pembrolizumab-EP continued to show clinically meaningful improvement in survival and manageable safety vs placebo-EP in patients with previously untreated ES-SCLC,” said Rudin. “Patients who completed 35 cycles of pembrolizumab had durable responses.”

“[Taken together, our] data support the continued exploration of pembrolizumab-based combinations for patients with ES-SCLC,” he concluded.