Found 1 Presentation For Request "424p"
424P - Avelumab added to FOLFIRI plus cetuximab followed by avelumab maintenance in patients with previously untreated RAS wild-type colorectal cancer: The phase-II FIRE-6 (AIO KRK-0118)
- Sebastian Stintzing (Berlin, Germany)
Abstract
Background
The FIRE-6 avelumab study (AIO KRK-0118) was performed in RAS-wild-type mCRC patients. This multi-center single-arm study tested the efficacy of avelumab maintenance during 1st-line therapy after 4 cycles of induction treatment with FOLFIRI plus cetuximab (FOLFIRI/Cet) followed by 4 cycles of combination treatment using FOLFIRI/Cet plus avelumab. Subsequently, treatment was continued with avelumab until progression or intolerable toxicity.
Methods
Patients received FOLFIRI (irinotecan plus 5-FU/FA) every two weeks plus cetuximab weekly at the standard dosing schedule. After 4 cycles of therapy, avelumab (10mg/kg q2w) was added to FOLFIRI/Cet and continued for another 4 cycles before maintenance with avelumab monotherapy was started. Median progression-free survival (PFS) according to RECIST v1.1 was evaluated as primary endpoint. With a target PFS ≥ 12.88 months, the study was designed to reject the null hypothesis of PFS ≤8.0 months with a power of 80% at a one-tailed significance level of 0.025. Secondary endpoints included ORR, OS, safety, and tolerability.
Results
From November 2019 to June 2021, 57 patients were treated within the study protocol. Treatment with FOLFIRI/Cet plus avelumab was well tolerated and no new or unexpected toxicities were observed. Median PFS was 7.0 months in 47 evaluable patients. Overall response rate was 73.2% with a disease control rate of 87.5%. Median time on avelumab maintenance was 1.9 months with a range up to 15.6 months. Median OS was not reached at the time of the latest data cut-off with only 21.4% of OS events had occurred.
Conclusions
With a median PFS of 7.0 months, FIRE-6 avelumab did not reach its pre-specified endpoint. Avelumab maintenance after FOLFIRI/Cet therefore is not effective to postpone disease progression after FOLFIRI/Cet induction therapy in first-line RASwt mCRC patients. Some long-term responders are present and will be further analyzed. FOLFIRI/Cet plus avelumab is safe and feasible as no unexpected toxicities occurred. FIRE-6 avelumab confirms the efficacy with respect to tumor response and disease control of FOLFIRI plus cetuximab as first-line treatment of patients with RAS wild-type mCRC.
Clinical trial identification
Protocol code: FIRE-6, EudraCT number: 2018-002010-12.
Legal entity responsible for the study
Klinikum der Universität München.
Funding
Merck KGaA, Darmstadt.
Disclosure
S. Stintzing: Financial Interests, Personal, Advisory Board: AMGEN, Bayer, BMS, Eisai, Lilly, Merck KGaA, MSD, Pierre Fabre, Roche, Sanofi, Servier, Taiho, Takeda; Financial Interests, Personal, Invited Speaker: AMGEN, Bayer, BMS, EISAI, Leo Pharma, Lilly, Merck KGaA, MSD, Pierre Fabre, Roche, Sanofi, Servier, Taiho, Takeda; Financial Interests, Institutional, Research Grant: Merck KGaA, Pierre Fabre, Servier, Roche. I. Schwaner: Financial Interests, Personal, Expert Testimony: Abbvie, Amgen, AstraZeneca, Beigene, BMS, Incyte, Janssen, Lilly, Roche, Servier. L. Fischer von Weikersthal: Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Pierre Fabre. V. Heinemann: Financial Interests, Personal, Expert Testimony: Merck, Amgen, Roche, Sanofi, SIRTEX, Servier, Pfizer, Pierre-Fabre, AstraZeneca; Financial Interests, Personal, Invited Speaker: Merck, Amgen, Roche, Sanofi, SIRTEX, BMS, MSD, Novartis, Boehringer-Ingelheim, Servier, Pierre Fabre, Celgene, Terumo; Financial Interests, Institutional, Research Grant: Merck, Amgen, Roche, Sanofi, Pfizer, Boehringer-Ingelheim, SIRTEX, Bayer, Servier; Financial Interests, Personal, Other, Travel accommodation expenses: Merck, Roche, Amgen, SIRTEX, Bayer, Servier. All other authors have declared no conflicts of interest.