KEY TAKEAWAYS
- The PAVE phase 2 trial aimed to investigate the efficacy of intercalated avelumab in patients with SCLC after induction chemotherapy.
- The primary endpoint was a 1-year PFS.
- The results demonstrated comparable efficacy despite failing to meet the primary endpoint.
Extensive stage small cell lung cancer (ES-SCLC) carries a dismal prognosis, with first-line chemo-immunotherapy emerging as the established standard of care.
Giannis Mountzios and the team aimed to assess whether administering immunotherapy after two cycles of induction chemotherapy, when neoantigen release is maximal, could improve immune response and overall efficacy.
The PAVE, a phase II multicenter study, combined the anti-PD-L1 antibody avelumab with platinum-etoposide in a single-arm trial. Before phase II, a safety run-in was conducted, wherein untreated patients with ES-SCLC received standard chemotherapy every 3 weeks for 4-6 cycles.
Avelumab 10 mg/kg was administered every 2 weeks from cycle 3 until chemotherapy completion and then as maintenance. The primary endpoint was 1-year progression-free survival (PFS). Genotyping of FFPE tumors via targeted NGS, tumor-infiltrating lymphocytes (TILs) density assessment, and analysis of CD8 and PD-L1 were performed.
About 55 patients were enrolled, with a median age of 65.9 years and 67.3% male. Common metastatic sites included the liver (54.5%), bone (32.7%), and brain (10.9%). With a median follow-up of 10.3 months, the one-year PFS rate was 12.7%, with a median PFS of 5.8 months. The one-year overall survival (OS) rate was 38.2%, with a median OS of 10.3 months.
Among all patients, the overall response rate (ORR) was 69.1%, with complete response (CR) in 5.5% and partial response (PR) in 63.6%, and a median duration of response (DOR) of 5.6 months. Adverse events of grade 3-4 occurred in 56% of patients. Quality of life (QoL), global health status, and disease-related symptoms significantly improved. TILs or CD8 presence did not hold predictive or prognostic value.
Nearly all tumors carried genetic alterations, with TP53 (89.5%), RB1 (57.9%), NOTCH (31.6%), and MYC (23.7%) being the most frequently altered genes. Liver metastases presence, RB1 or TP53/RB1 co-mutations, absence of prophylactic cranial irradiation (PCI), and older age (>65 years) were negative prognostic factors for both PFS and OS.
The findings suggested that the primary endpoint of 1-year PFS was not achieved by intercalated avelumab treatment in conjunction with platinum-etoposide.
The trial was sponsored by the Hellenic Cooperative Oncology Group.
Clinical Trial: https://clinicaltrials.gov/study/NCT03568097
Mountzios G, Korfiatis N, Goussia A, et al. (2024) “Final outcome, immunophenotypic and biomarker analysis of intercalated avelumab plus platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (PAVE): A pilot phase II study of the Hellenic co-operative oncology group.” Presented at ELCC 2024. Annals of Oncology (2024) 9 (suppl_3): 1-11. 10.1016/esmoop/esmoop102577 (197MO)
