On June 18, 2019, the United States Food and Drug Administration granted accelerated approval to the PD-1 inhibitor pembrolizumab for use as a monotherapy in the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other line of therapy. This approval was based on pooled data from 2 multicenter, multicohort, nonrandomized, open-label trials, KEYNOTE-158 and KEYNOTE-028. Among the 73 patients included in the efficacy analysis, pembrolizumab monotherapy resulted in an overall response rate of 19%, including 2% complete response and 17% partial response. Responses were durable, and 94% of responding patients had a duration of response (DOR) of more than 6 months and 56% had a DOR greater than 18 months. The safety analysis (n = 131) was consistent with the known adverse event (AE) profile of pembrolizumab in lung cancer. Full approval for pembrolizumab in this indication is contingent upon confirmation of clinical benefit.
High Altitude: The approval of pembrolizumab in this setting represents a major advance, not just for SCLC but also in terms of drug development. This is one of several approvals for pembrolizumab to come from the KEYNOTE-028 basket trial. Basket trials allow investigators to assess the efficacy of a novel treatment approach in a number of tumor types. However, these trials have been historically limited to early development and hypothesis generation rather than for registration, as the US FDA has typically required indication-specific studies. This approval, along with recent approvals of targeted therapies for multiple cancer indications, could represent a new era in drug development. This new regulatory perspective will likely foster further innovations in study design because drug development might no longer be bound by the classic large-scale randomized controlled trial design, aiming for a single indication, that has been the cornerstone of the drug approval process for the last half century.
Ground Level: Chemotherapy-refractory SCLC has been an area of unmet medical need. The approval of pembrolizumab introduces an important additional treatment option. Pembrolizumab is well known to lung cancer specialists, being already an established treatment approach for patients with non-small cell lung cancer. Many of the oncologists treating SCLC will be familiar with its administration and AE management. In the updated prescribing information, the AE profile in SCLC is reported to be similar to that in other solid tumors. As the drug is already commercially available, patients may approach their oncologists to request treatment sooner than with other newly approved agents. It will be important to tailor their expectations in terms of likelihood of benefit and side effects.