Small results.

Top Line: Immune checkpoint inhibitor (ICI) options for extensive-stage small cell lung cancer (ES-SCLC) are expanding.

The Study: Recall IMpower133 where adding atezolizumab to platinum and etoposide improved median overall survival (OS) from 10 → 12 months and 1-year OS 38 → 52%. Likewise, adding durvalumab to PE improved median OS 10 → 13 months and 1-year OS 40 → 54% in CASPIAN. Here we have the results of KEYNOTE-604, which asked the same question using PE +/- concurrent and maintenance pembrolizumab. Over 450 patients with de novo ES-SCLC were randomized, and those with brain mets (10-15%) were allowed to enroll after intracranial treatment. Prophylactic cranial irradiation was also allowed, at clinician discretion, after a partial or complete response to the cytotoxic chemo component. Overall, 41% of patients had any tumor PD-L1 expression. Unlike atezo and durvalumab, adding pembro to PE did not improve median OS (10 → 11 months) nor 1-year OS (40 → 45%). Pembro did improve progression-free survival (PFS) at 12 months from 3 → 14%. The authors encourage us not to discount the benefit of pembro too soon as survival curves separated over time with a more significant-appearing improvement in OS at 24 months. Sound familiar? The Slotman trial back in 2014 showed us that thoracic radiation for ES-SCLC that responds to initial therapy also significantly improved PFS with a similar improvement in 24-month OS. Was that treatment allowed in KEYNOTE-604? Of course not.

TBL: Pembro, unlike atezo and durvalumab, does not improve survival when added to front-line platinum and etoposide for metastatic small cell lung cancer. | Rudin, J Clin Oncol 2020