Abstract 32P
Background
In CodeBreak 300 (NCT05198934), a phase 3 study evaluating two doses of soto (960 mg and 240 mg) + pani against investigator’s choice of T/T or rego in pts with chemorefractory KRAS G12C-mutated mCRC, both doses of soto resulted in better health-related quality of life (HRQOL) and a trend to decreased risk of deterioration. Here, we present patient-reported tolerability from CodeBreaK 300.
Methods
Patient-reported tolerability was assessed using the Functional Assessment of Cancer Therapy - General (FACT-G) item GP5 (“I am bothered by side effects of treatment”) at study baseline and every 4 weeks thereafter. Responses to the FACT-G GP5 item were rated on a 5-point Likert scale from “Not at all” to “Very much”. Patient-reported tolerability was also assessed by skin toxicity adverse event per CTCAE v5.0 in pts receiving soto + pani based on pooled data from the two arms. Patient-reported outcome (PRO) scores were summarized descriptively in pts who had a baseline and at least one postbaseline PRO score.
Results
Of the 160 randomized pts, 129 (81%) were included in this analysis. Patient’s side effect bother at baseline and week 9 was comparable across all three arms (Table). Among pts treated with soto + pani, pts experiencing grade ≥ 2 skin toxicity reported more “Quite a bit” or “Very much” side effect bother at week 9 than pts experiencing grade ≤ 1 (23% vs 10%); however, this difference was transient. Table: 32P
| Time point | Likert rating | Soto 960 mg + pani | Soto 240 mg + pani | Investigator’s choice |
| Baseline | Number of pts | 41 | 45 | 43 |
| Not at all / A little bit | 85% | 89% | 91% | |
| Somewhat | 10% | 2% | 7% | |
| Quite a bit / Very much | 5% | 9% | 2% | |
| Week 9 | Number of pts | 31 | 33 | 17 |
| Not at all / A little bit | 74% | 67% | 65% | |
| Somewhat | 13% | 21% | 24% | |
| Quite a bit / Very much | 13% | 12% | 12% |
Conclusions
PRO scores suggest that soto + pani do not increase general side effect bother more than T/T or rego despite an increase in skin toxicity. Altogether, PRO scores complement previously reported improvements in clinical outcomes and HRQOL, thus supporting soto 960 mg + pani as a potential standard of care in pts with KRAS G12C-mutated chemorefractory mCRC.
Clinical trial identification
NCT05198934.
Editorial acknowledgement
Medical writing support was provided by Marlesa Godoy, PhD (Amgen Inc.) and Christopher Nosala, PhD, CMPP (Amgen Inc.).
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis, Pfizer; Financial Interests, Personal, Expert Testimony: Astellas; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis; Non-Financial Interests, Leadership Role, President of the scientific committee of the ARCAD foundation until end 2022: ARCAD Foundation; Non-Financial Interests, Leadership Role, Chair of the ARCAD pancreas research group: ARCAD Foundation; Non-Financial Interests, Leadership Role, Member of the administrative council, the scientific committee, the executive board and responsible for the international relationships /partnership for FFCD in the prodige intergroup: Federation Francophone de Cancerologie Digestive (FFCD). M. Fakih: Financial Interests, Personal, Advisory Board, Consultant: AstraZeneca, Bayer Corporation, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, One meeting: Eisai Oncology; Financial Interests, Personal, Advisory Board, One meeting: Entos, Merck, Seattle Genetics, Xenthera; Financial Interests, Personal, Advisory Board, Also Editorial Boards & Consulting: Mirati Therapeutics; Financial Interests, Personal, Advisory Board: Nouscom, Roche/Genentech; Financial Interests, Personal, Advisory Board, Consulting: Pfizer, Taiho Oncology; Financial Interests, Institutional, Research Grant: AgenusBio, Genentech/imCORE, Verastem. L. Salvatore: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bayer, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Servier; Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Servier; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Bayer, Celgene, Merck Serono, Pierre Fabre, Sanofi, Servier. T. Esaki: Financial Interests, Personal, Invited Speaker: Chugai, Taiho, EP force, MSD, Daiichi Sankyo, Eli Lilly, Ono, Bristol; Financial Interests, Institutional, Research Grant: MSD, Novartis, Ono, Nihon Kayaku, IQVIA, Daiichi Sankyo, Chugai, Syneos Health Clinical, Pfizer, Dainippon Sumitomo, Quintiles, Eli Lilly, Parexel, Astellas, Astellas Amgen Biopharma, Eisai, Bayer, Asahikasei Pharma; Financial Interests, Institutional, Funding: Chugai, Nihon Kayaku. D.P. Modest: Financial Interests, Personal, Invited Speaker: Takeda, Taiho, Amgen, Servier, Merck, Onkowissen, MSD, AstraZeneca, Pierre Fabre, GSK, Medison, COR2ED, JE, 21up, Seagen; Financial Interests, Personal, Advisory Board: Amgen, Servier, Merck, MSD, Takeda, G1, Onkowissen, Pierre Fabre, AstraZeneca, Regeneron; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Invited Speaker: Servier. D. Paez: Financial Interests, Personal, Advisory Role: Amgen, Esteve; Financial Interests, Personal, Speaker’s Bureau: Amgen, MSD, Novartis; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Amgen, Ipsen, Lilly, Merck KGaA, Sanofi. M.V. Karamouzis: Financial Interests, Personal, Other, Honoraria: Astellas Pharma, BMS, MSD, Pfizer Hellas, Roche, Servier; Financial Interests, Personal, Speaker’s Bureau: BMSi; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Ipsen. E. Ruiz: Financial Interests, Personal, Advisory Board: Roche, Amgen, BMS, Bayer, Pfizer; Financial Interests, Personal, Invited Speaker: Roche, Merck, Astellas; Non-Financial Interests, Member: ASCO. T.W. Kim: Financial Interests, Institutional, Research Grant: Genentech, Genome insight. Y. Kuboki: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb Japan, Lilly Japan, Taiho Pharmaceutical, Takeda; Financial Interests, Personal, Advisory Role: Amgen, Boehringer Ingelheim, Incyte, Janssen Oncology, Takeda; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Amgen, Incyte; Financial Interests, Institutional, Research Grant: AbbVie, Amgen, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Chugai Pharma, Genmab, GSK, Incyte, Janssen Oncology, Jiangsu Hengrui Pharmaceuticals, Lilly, Merck Serono, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda. D. Cunningham: Financial Interests, Personal, Stocks/Shares: Ovibio; Non-Financial Interests, Personal, Advisory Board: Ovibio; Financial Interests, Institutional, Research Grant: 4SC, Bayer, Clovis Oncology, Leap Oncology, Lilly, MedImmune, Roche. K. Yeh: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, PhytoHealth, Novartis, Ono, Merck, AstraZeneca, Pierre Fabre, MSD, Bayer; Non-Financial Interests, Member: American Society of Clinical Oncology, American Association for Cancer Research. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Pierre Fabre, Nordic Pharma, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Institutional, Invited Speaker: Roche, Bayer, Servier, Merck, Seagen, Hutchinson. J. Wang: Financial Interests, Personal, Full or part-time Employment: RTI Health Solutions. Q. Tran: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. J. Chao: Financial Interests, Personal, Advisory Board: Merck, Amgen, Daiichi Sankyo, Bristol Myers Squibb, Astellas, Turning Point Therapeutics, Silverback Therapeutics, Guardant Health, Novartis, Geneos; Financial Interests, Personal, Invited Speaker: Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting: Lilly, AstraZeneca, Roche, Coherus Biosciences, Foundation Medicine; Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Institutional, Funding: Merck, Brooklyn Immunotherapeutics. Z. Chen: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. F. Pietrantonio: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, MSD, Bayer, Organon, Astellas; Financial Interests, Personal, Invited Speaker: Amgen, Merck Serono, BMS, Lilly, Servier, Bayer, Pierre Fabre, AstraZeneca, Astellas; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Incyte, Agenus. All other authors have declared no conflicts of interest.