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Clinical Trial
. 2025 Oct 1:228:115660.
doi: 10.1016/j.ejca.2025.115660. Epub 2025 Jul 25.

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

Helena Linardou  1 , Kyriaki Papadopoulou  2 , Nikolaos Korfiatis  3 , Anna Goussia  4 , Epaminondas Samantas  5 , Gerasimos Aravantinos  6 , Athina Christopoulou  7 , Nikolaos Spathas  8 , Elena Fountzilas  9 , Amanda Psyrri  10 , Georgia-Angeliki Koliou  11 , Soultana Meditskou  12 , Epaminondas Kosmas  13 , Mattheos Bobos  2 , Antonia V Charchanti  14 , Ioannis Vamvakaris  15 , Anna Koumarianou  16 , Dimitrios Bafaloukos  17 , Paris Kosmidis  18 , George Fountzilas  19 , Giannis Mountzios  20
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Free article
Clinical Trial

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

Helena Linardou et al. Eur J Cancer. .
Free article

Abstract

Background: Extensive 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.

Methods: PAVE 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.

Results: Between 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 < 65 years old and most with ≤ 3 metastatic sites (50 %). Median OS of the LTS was 34.2 months and median PFS 19.9 months.

Conclusions: Intercalated avelumab administration with chemotherapy did not meet the primary endpoint of 1-year PFS. However, our results suggest that this approach demonstrates clinically relevant PFS, DoR, and improved QoL, with overall outcomes similar to those seen with standard frontline chemotherapy in historical controls.

Keywords: Avelumab; Clinical trials; Immunotherapy; Lung neoplasms; Phase II; Platinum-based chemotherapy; Small Cell Lung Cancer.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Helena Linardou: Advisory/Consultation Fees from Roche, Astra Zeneca, Novartis, BMS, MSD, Pfizer, Amgen and Merck. Epaminondas Samantas: Advisory Board of Merck, MSD, Asta-Zeneca, Roche, Amgen and Genesis. Gerasimos Aravantinos: Advisory Boards: Novartis, BMS, Roche Hellas, Astra Zeneca, Sanofi, Amgen, Genesis Pharma, Merck, Pfizer. Athina Christopoulou: Advisory and sponsored conferences: Astra, Roche, MSD, BMS, Sanofi, Amgen, Pfizer, Novartis. Nikolaos Spathas: Honoraria/Speaker: Roche, BMS, Astra-Zeneca, Travel: Sanofi, Amgen, Roche. Elena Fountzilas: Advisory Role: Amgen LEO Pharma. Speaker fees: Roche, Pfizer, AstraZeneca, Amgen. Travel grant: AstraZeneca, Merck, Pfizer and DEMO. Stock ownership: Genprex Inc., Deciphera Pharmaceuticals Inc. A. Psyrri: Consultation Fees: Amgen, Merck Serono, Roche, BMS, AstraZeneca, MSD. Honoraria: Amgen, Merck Serono, Roche, BMS, AstraZeneca, MSD. Research funding: BMS, Kura Oncology, DEMO, Roche. Anna Koumarianou: Advisory Role: Genesis Pharma. Honoraria: Pfizer. Speaker’s bureau: Roche. Research Funding: Merck. Travel: MSD. Educational grants: Novartis, Pfizer, Merck, Roche, BMS, MSD, Genesis, and Ipsen. Paris Kosmidis: Advisory board: Bristol, Gilead, Lilly. Travel Congress sponsor: MSD, Pfizer. George Fountzilas: Advisory Board of Pfizer, Novartis. Honoraria from AstraZeneca, Novartis. Stock ownership: Genprex, Daiichi Sankyo, RFL Holdings, FORMYCON. Giannis Mountzios: Advisory and consultation fees: AstraZeneca, BMS, MSD, Roche, Takeda, Novartis, AMGEN, Pfizer, Takeda, GSK, Sanofi. Travel and accommodation fees: AstraZeneca, BMS, MSD, Roche, Takeda, Novartis, GSK, Sanofi, Αmgen. PI in sponsored clinical trials: Novartis, Roche, MSD, AstraZeneca, Merck, ΒΜS, AMGEN, Ιmmunomedics, GSK, Sanofi, Gilead. The rest of the authors declare No Conflict of Interest.

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