Intercalated Avelumab Plus Chemotherapy Demonstrates Promise Among Patients With Extensive-Stage Small Cell Lung Cancer

According to final immunophenotypic and biomarker analysis results from the phase 2 PAVE study, intercalated avelumab plus chemotherapy demonstrated promising efficacy and safety among patients with extensive-stage small cell lung cancer (ES-SCLC). 

“[ES-SCLC] has poor prognosis, and first-line chemo-immunotherapy is now the standard-of-care,” stated Helena Linardou, MD, PhD, Metropolitan Hospital, Athens, Greece, and coauthors. “We hypothesized that intercalated immunotherapy administration in-between chemotherapy cycles, at maximal neoantigen release, might enhance immune response and efficacy.”

In this multicenter study, 55 previously untreated patients received standard platinum-etoposide once every 3 weeks for 4 to 6 cycles plus 10 mg/kg of avelumab once every 2 weeks starting at cycle 3 followed by avelumab maintenance. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS), objective response rate (ORR), duration of response, safety, and quality of life.  

At a median follow-up of 10.3 months, the 1-year PFS rate was 12.7% and median PFS was 5.8 months. The 1-year OS rate was 38.2% and median OS was 10.3 months. The ORR was 69.1% and the median duration of response was 5.6 months. Grade 3/4 adverse events occurred in 56% of patients. Quality of life measures including global health status and disease-related symptoms significantly improved from baseline. The presence of TILs and CD8 was not significantly correlated with survival outcomes. All but 1 tumor carried genetic alterations, most frequently including TP53 (89.5%), RB1 (57.9%), NOTCH (31.6%), and MYC (23.7%). 

Negative prognosticators of survival included presence of liver metastases, presence of RB1 or TP53/RB1 co-mutations, no prior prophylactic cranial irradiation, and an age of > 65. Researchers identified 10 long-term survivors who were < 65 years, 50% of which had ≤ 3 metastatic sites. Among long-term survivors, median PFS was 19.9 months, and median OS was 34.2 months. 

“Intercalated avelumab administration with chemotherapy did not meet the primary end point of 1-year PFS,” concluded Dr Linardou et al. “However, our results suggest that this approach demonstrates clinically relevant PFS, [duration of response and improved quality of life], with overall outcomes similar to those seen with standard frontline chemotherapy in historical controls.” 

Source: 

Linardou H, Papadopoulou K, Korfiatis N, et al. Intercalated avelumab plus platinum-based chemotherapy in patients with extensive-stage small-cell lung cancer (PAVE): Final outcome, immunophenotypic and biomarker analysis of a multi-center phase II Hellenic Cooperative Oncology Group study. Eur J Cancer. Published online: July 25, 2025. doi: 10.1016/j.ejca.2025.115660