Abstract 1648P
Background
Prognosis of extensive stage small cell lung cancer (ES SCLC) remains poor. Recently chemo-immunotherapy became the 1st line standard of care. We hypothesized that phased administration of immunotherapy after 2 initial chemotherapy cycles, when neoantigen release is maximized and patient PS improved, might enhance the immune response.
Methods
This is an investigator initiated single arm multicenter phase II study of anti-PDL1 avelumab combined with platinum-etoposide. A safety run in preceded the phase II part, where patients with measurable untreated ES SCLC, ECOG PS 0-1 received standard Cisplatin or Carboplatin + Etoposide chemotherapy q 3 weeks for 4-6 cycles and Avelumab 10 mg/kg q 2 weeks starting from cycle 3 until chemo completion and as maintenance thereafter. Primary endpoint was 1-year progression free survival (PFS), secondary endpoints PFS, overall survival (OS), objective response rate (ORR), duration of response (DOR), toxicity, quality of life (QoL questionnaires EQ-5D, EORTC QLQ-C30, -LC13).
Results
From 09/2018 to 09/2020, 55 patients median age 66 years, 67% males, 33% ECOG PS 1 were enrolled. Metastatic sites included liver 26.7%, bone 40%, previously irradiated brain 6.7%. At median follow-up 17 months (95% CI 12.8-25.7) 39 patients had died (70.9%). Median duration of avelumab treatment was 4.1 months (range 0-27.2). Efficacy shown in the table. Any cause adverse events (AEs) grade 3-4 occurred in 61.8% patients with 2 deaths due to AEs not related to avelumab. QoL, global health status, disease or treatment -related symptoms were significantly improved. Table: 1648P
| 1-year PFS (%) | Median PFS (months) | 6-month OS (%) | 1-year OS (%) | Median OS (months) | ORR (%) | CR (%) | PR (%) | SD (%) | Median DOR (months) | |
| Result | 18.3 | 5.7 | 72.7 | 39 | 10.4 | 65.5 | 3.6 | 61.8 | 12.7 | 5.6 |
| 95% CI | 7.7-28.9 | 4.9-7.2 | 61.0-84.5 | 25.2-52.9 | 7.5-13.8 | 51.4-77.8 | 0.4-12.5 | 47.7-74.6 | 5.3-24.5 | 4.1-6.8 |
Conclusions
Phased avelumab and platinum-etoposide showed comparable efficacy to published frontline chemo-immunotherapy combinations with clinically relevant PFS, DOR, improved QoL and no unexpected toxicities. These results warrant further investigation of phased avelumab-chemotherapy combination as frontline option in ES SCLC.
Clinical trial identification
NCT03568097.
Editorial acknowledgement
Legal entity responsible for the study
Hellenic Cooperative Oncology Group.
Funding
This is a Hellenic Cooperative Oncology Group initiated research, which was financially supported by Merck A.E., Greece, an affiliate of Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer.
Disclosure
H. Linardou: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Invited Speaker: Roche; Financial Interests, Personal and Institutional, Invited Speaker: AbbVie; Financial Interests, Personal and Institutional, Invited Speaker: Lilly; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker: Amgen; Financial Interests, Personal and Institutional, Invited Speaker: PPD; Financial Interests, Personal and Institutional, Invited Speaker: Parexel ILR; Financial Interests, Personal and Institutional, Invited Speaker: Qualitis; Financial Interests, Personal and Institutional, Invited Speaker: Health Data Specialist; Non-Financial Interests, Principal Investigator: Hellenic Cooperative Oncology Group; Non-Financial Interests, Leadership Role, Elected President of the Scientific Committee: Hellenic Cooperative Oncology Group; Non-Financial Interests, Invited Speaker: Women 4 Oncology - Hellas; Non-Financial Interests, Invited Speaker: Fairlife Lung Cancer Care. E. Samantas: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Genesis. E. Fountzilas: Financial Interests, Personal, Advisory Role: Leo Pharma; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Genprex Inc.; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals, Inc.; Financial Interests, Personal, Other, Travel grant: Merck; Financial Interests, Personal, Other, Travel grant: Pfizer; Financial Interests, Personal, Other, Travel grant: K.A.M Oncology/Haematology; Financial Interests, Personal, Other, Travel grant: Demo. A.N. Christopoulou: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Sponsored Conferences: AstraZeneca; Financial Interests, Personal, Other, Sponsored Conferences: Roche; Financial Interests, Personal, Other, Sponsored Conferences: MSD; Financial Interests, Personal, Other, Sponsored Conferences: BMS; Financial Interests, Personal, Other, Sponsored Conferences: Sanofi; Financial Interests, Personal, Other, Sponsored conferences: Amgen; Financial Interests, Personal, Other, sored conferences: Pfizer; Financial Interests, Personal, Other, Sponsored conferences: Novartis. A. Psyrri: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: Kura. E. Kosmas: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Chiesi; Financial Interests, Personal, Invited Speaker: Vianex Hellas; Financial Interests, Personal, Invited Speaker: Elpen Hellas; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Menarini; Financial Interests, Personal, Invited Speaker: Vocate; Financial Interests, Personal, Invited Speaker: CSL Behring; Financial Interests, Personal, Writing Engagements: Menarini; Financial Interests, Personal, Writing Engagements: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Chiesi; Financial Interests, Personal, Speaker’s Bureau: Vianex Hellas; Financial Interests, Personal, Speaker’s Bureau: Elpen Hellas; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Menarini; Financial Interests, Personal, Speaker’s Bureau: CSL Behring; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Chiesi; Financial Interests, Personal, Advisory Board: Elpen Hellas; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Menarini; Financial Interests, Personal, Advisory Board: Vocate; Financial Interests, Personal, Advisory Board: CSL Behring; Financial Interests, Personal, Principal Investigator: Menarini; Financial Interests, Personal, Principal Investigator: Boehringer Ingelheim; Financial Interests, Personal, Principal Investigator: Novartis. A. Koumarianou: Financial Interests, Personal, Advisory Role: Genesis Pharma; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Other, Travel grant: MSD; Financial Interests, Personal, Other, Educational grant: Novartis; Financial Interests, Personal, Other, Educational grant: Pfizer; Financial Interests, Personal, Other, Educational grant: Merck; Financial Interests, Personal, Other, Educational grant: Roche; Financial Interests, Personal, Other, Educational grant: BMS; Financial Interests, Personal, Other, Educational grant: MSD; Financial Interests, Personal, Other, Educational grant: Genesis Pharma; Financial Interests, Personal, Other, Educational grant: Ipsen. G. Fountzilas: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Genprex; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Ariad; Financial Interests, Personal, Stocks/Shares: RFL Holdings; Financial Interests, Personal, Stocks/Shares: Formycon. G. Mountzios: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Advisory Role: Boehringer; Financial Interests, Personal, Other, Honoraria: Boehringer; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Travel grant: AstraZeneca; Financial Interests, Personal, Other, Travel grant: Roche; Financial Interests, Personal, Other, Travel grant: Pfizer; Financial Interests, Personal, Other, Travel grant: BMS; Financial Interests, Personal, Other, Travel grant: MSD; Financial Interests, Personal, Other, Travel grant: Takeda; Financial Interests, Personal, Other, Travel grant: Boehringer; Financial Interests, Personal, Other, Travel grant: Merck; Financial Interests, Personal, Other, Travel grant: Novartis; Financial Interests, Personal, Other, Travel grant: Astellas; Financial Interests, Personal, Other, Travel grant: Pierre Fabre. All other authors have declared no conflicts of interest.