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.

BackgroundExtensive stage small cell lung cancer (ES-SCLC) has poor prognosis, and first-line chemo-immunotherapy is now the standard-of-care. We hypothesized that intercalated immunotherapy administration in-between chemotherapy cycles, at maximal neoantigen release, might enhance immune response and efficacy.MethodsPAVE is a multicenter phase II study. Patients with untreated ES-SCLC received standard platinum-etoposide every three weeks for 4-6 cycles. Avelumab 10mg/kg was administered every two weeks from cycle 3 until chemotherapy completion, and as maintenance thereafter. The primary endpoint was one-year PFS. Genotyping of FFPE tumors via targeted NGS, assessment of tumor-infiltrating lymphocytes (TILs) and analysis of CD8 and PD-L1, was performed.ResultsBetween September 2018-September 2020, 55 pts, median age 65.9 years, 67.3 % male, were enrolled. With median follow-up of 10.3 months, 1-year PFS was 12.7 %, median PFS 5.8 months, 1-year OS 38.2 %, median OS 10.3 months. ORR was 69.1 % (CR 5.5 %, PR 63.6 %), median DoR 5.6 months. AEs grade 3-4 occurred in 56 % of patients. QoL, global health status and disease-related symptoms were significantly improved from baseline. The presence of TILs/CD8 in tumour was not significantly associated with survival. All but one tumor carried genetic alterations, with TP53 (89.5 %), RB1 (57.9 %), NOTCH (31.6 %) and MYC (23.7 %) being the most frequently mutated genes. Liver metastases, RB1 or TP53/RB1 co-mutations, no PCI and age > 65 years were negative PFS/ OS prognosticators. There were 10 Long Term Survivors (LTS) identified, the majority