In Phase II study for extensive-stage small-cell lung cancer (ES-SCLC), the novel intercalated administration of the anti-PD-L1 inhibitor avelumab with platinum-etoposide chemotherapy (avelumab started after cycle 2) did not meet the primary endpoint of a 25% one-year progression-free survival (PFS), achieving 12.7% (median PFS: 5.8 months).
Despite this, the treatment demonstrated high anti-tumor activity with an Objective Response Rate (ORR) of 69.1% and a one-year Overall Survival (OS) rate of 38.2% (median OS: 10.3 months), which is comparable to other chemo-immunotherapy regimens. The regimen was well-tolerated with no new safety signals, and it maintained or improved Quality of Life (QoL), specifically reducing dyspnea and cough.
Prognostic analysis identified liver metastases as an independent negative prognostic factor and confirmed that receiving Prophylactic Cranial Irradiation (PCI) significantly improved PFS and OS. Molecularly, co-mutations in TP53 and RB1 were associated with a shorter PFS. While ten Long-Term Survivors (LTS) were identified with a median OS of 34.2 months, no specific molecular marker distinguished them. The authors suggest that although the primary endpoint was missed, the observed meaningful responses and QoL benefits warrant further exploration of optimized immunotherapy strategies in selected ES-SCLC patients.