559MO - Rechallenge with EGFR inhibitors in ctDNA RAS/BRAF wild type refractory metastatic colorectal cancer: Individual patients’ data pooled analysis from 4 phase II trials

Background

Rechallenge with anti-EGFR inhibitors demonstrated clinical activity in patients (pts) with refractory circulating tumor DNA (ctDNA) RAS/BRAF wild type (wt) metastatic colorectal cancer (mCRC) and it is included as an option in clinical guidelines. However, the available evidence (III C) is derived from small retrospective/prospective studies.

Methods

We conducted an individualized patients’ data pooled analysis of pts enrolled in the CAVE, VELO, CRICKET and CHRONOS trials treated with anti-EGFR rechallenge with RAS/BRAF wt ctDNA. Overall survival (OS), progression free survival (PFS), overall response rate (ORR) and disease control rate (DCR) were calculated. Safety was reported.

Results

Overall, 114/194 pts that received anti-EGFR rechallenge as experimental therapy (48 cetuximab plus avelumab, 26 trifluridine/tipiracil plus panitumumab, 13 irinotecan plus cetuximab and 27 panitumumab) had RAS/BRAF wt baseline plasma ctDNA and were included in the current analysis. The study population included heavily pre-treated pts: 83/114 (72.8%) and 31/114 (27.2%) pts received rechallenge with EGFR inhibitors as third- or later lines of treatment, respectively. Median PFS (mPFS) and median OS (mOS) were 4.0 months (95% CI, 3.2-4.7) and 13.1 months (95% CI, 9.5-16.7). One patient achieved complete response (CR), 19 pts displayed partial response (PR), while 65 and 29 had stable disease (SD) and progressive disease as best response, respectively. The ORR (CR+PR) was 17.5% (20/114); DCR (CR+PR+SD) was 74.6% (85/114). Almost one of three pts significantly benefited from anti-EGFR rechallenge therapy (6-months PFS rate, 32.5%; 18-months OS rate, 31.6%). Treatments showed manageable toxicity, in lines with previous findings.

Conclusions

Results of this individual patients’ pooled analysis demonstrate promising clinical activity of rechallenge with EGFR inhibitors with nearly one-third of the pts experiencing long PFS that lead to prolonged survival. Thus, rechallenge with anti-EGFR-based strategies might be considered as a therapeutic option in the continuum of care of pts with refractory ctDNA RAS/BRAF wt mCRC.

Clinical trial identification

NCT05291156; NCT05468892; NCT02296203; NCT03227926.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Regione Campania; Merck Serono; Amgen.

Disclosure

D. Ciardiello: Financial Interests, Personal, Other, Travel Support: Merck Serono, Bristol Myers Squibb, Sanofi. D. Rossini: Financial Interests, Personal, Speaker, Consultant, Advisor: Takeda. A. Avallone: Financial Interests, Personal, Advisory Board: Amgen, Servier. F. Pietrantonio: Financial Interests, Personal, Advisory Board: Amgen, Roche, Lilly, Sanofi, Bayer; Financial Interests, , Advisory Board: Merck Serono, Servier. S. Lonardi: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, Lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi Sankyo, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Pierre Fabre, GSK, Roche, Astellas; Financial Interests, Institutional, Coordinating PI: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, Bristol Myers Squibb. G. Masi: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Amgen. S. Siena: Financial Interests, Personal, Advisory Board, Advisory Board Member: Agenus, AstraZeneca, Bristol Myers Squibb, Checkmab, Daiichi Sankyo, GSK, Novartis, Seagen, T-One-Therapeutics. A. Bardelli: Financial Interests, Personal, Advisory Board: NeoPhore, Inivata; Financial Interests, Personal, Research Funding: AstraZeneca, Boehringer Ingelheim; Financial Interests, Personal, Other, shareholder: NeoPhore . F. Ciardiello: Financial Interests, Personal, Advisory Board: Roche, Merck Serono, Servier, Pierre Fabre, Pfizer; Financial Interests, Institutional, Research Grant: Merck Serono, Roche, Amgen; Financial Interests, Institutional, Local PI: Pfizer, Pierre Fabre, Servier. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Amgen, Pierre Fabre, Nordic Pharma; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Institutional, Coordinating PI: Roche, Bayer, Servier, Merck; Financial Interests, Institutional, Local PI: Seagen, Hutchinson. A. Sartore Bianchi: Financial Interests, Personal, Advisory Board: Amgen, Bayer, Servier, Novartis, Sanofi. T. Troiani: Financial Interests, Personal, Advisory Board: Roche, Merck Serono, Sanofi, Servier, Novartis, Bayer. E. Martinelli: Financial Interests, Personal, Invited Speaker: Merck Serono, Bayer, Merck, ESMO; Financial Interests, Personal, Writing Engagement, Advisory board and invited speaker and travel grant: Pierre Fabre; Financial Interests, Personal, Writing Engagement, Advisory board and Invited speakers: Incyte; Financial Interests, Personal, Writing Engagement, Advisory board and invited speaker: Servier, Roche; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Writing Engagement, Travel grant: AstraZeneca; Financial Interests, Personal, Writing Engagement, Advisory board: MSD. All other authors have declared no conflicts of interest.