4O - Patient-reported outcomes from the CodeBreaK 200 phase III trial comparing sotorasib versus docetaxel in KRAS G12C-mutated NSCLC

Background

In the CodeBreaK 200 phase III trial, sotorasib significantly improved PFS (primary endpoint) versus docetaxel in previously treated KRAS^G12C-mutated NSCLC. Previously described patient-reported outcomes (PROs) favored sotorasib over docetaxel for global health status, physical functioning, dyspnea, and cough (ESMO 2022, LBA10). Here, we report the severity and impact of symptoms on patients’ quality of life (QOL) in response to treatment.

Methods

In this trial, 345 patients who progressed after receiving platinum-based chemotherapy and a checkpoint inhibitor were randomized 1:1 to receive sotorasib (960 mg orally QD) or docetaxel (75 mg/m² intravenously Q3W). Well-established, validated questionnaires captured patients’ perception of their QOL and symptom burden: EuroQOL-5 Dimension Visual Analogue Scale (EQ-5D VAS), PRO-Common Terminology Criteria for Adverse Events (CTCAE), Brief Pain Inventory (BPI), and question GP5 from the Functional Assessment of Cancer Therapy Tool General form (FACT-G). For ordinal outcomes, change from baseline to week 12 was assessed with generalized estimating equations.

Results

Compared with patients receiving sotorasib, those receiving docetaxel were more severely bothered by their side effects (odds ratio [OR] 5.71) and experienced symptoms at a higher severity (pain: OR 2.94, aching muscles: OR 4.40, aching joints: OR 4.17, mouth or throat sores: OR 4.26). Further their symptoms more strongly interfered with their usual/daily activities (pain: OR 3.18, aching muscles: OR 3.90, aching joints: OR 10.68). QOL worsened five days after initial docetaxel treatment while remaining stable with sotorasib (change from baseline in VAS score: –8.4 vs 1.5). The VAS showed a long-term worsening of QOL with docetaxel while the VAS remained stable with sotorasib (–5.8 vs 2.2 at week 12).

Conclusions

Patients treated with sotorasib reported less severe symptoms than those treated with docetaxel; hence, their daily lives were positively affected. In addition to improving clinical efficacy outcomes, sotorasib maintained QOL versus docetaxel suggesting that sotorasib may be a more tolerable treatment option for patients with pretreated, KRAS^G12C-mutated advanced NSCLC.

Clinical trial identification

NCT04303780.

Editorial acknowledgement

Medical writing support provided by Dr. Kristina Y. Aguilera (Ph.D.), Amgen Inc.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

D.M. Waterhouse: Financial Interests, Personal, Invited Speaker, Speaker, Advisory Event, Travel: BMS; Financial Interests, Personal, Invited Speaker, Speaker, Advisory Event: AstraZeneca, Janssen, EMD Serono; Financial Interests, Personal, Invited Speaker, Speaker, Advisory Event, Consultant: Amgen, Merck; Financial Interests, Personal, Advisory Role, Advisory Event, Consultant: Jazz Pharmaceuticals, Fresenius Kbi; Financial Interests, Personal, Advisory Role, Advisory Event: Exelixis, Eisai, Pfizer, Mirati, Regeneron/Sanofi, Eli Lilly, Sanofi, Astellas, Gilead. S. Rothschild: Financial Interests, Personal and Institutional, Advisory Role, Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Eisai, Eli Lilly, Merck Serono, MSD Oncology, Novartis, Roche Pharma AG, Takeda, Amgen, Otsuka; Financial Interests, Institutional, Funding: AbbVie, Bristol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, Merck Serono, Roche Pharma AG; Financial Interests, Personal, Other, Travel, accommodations, expenses: Sanofi, Roche Pharma AG, Bristol-Myers Squibb, MSD Oncology, AstraZeneca, Takeda, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Other: Federal Drug Commission of the Federal Office of Public Health, Swiss Group for Clinical Cancer Research (SAKK); Financial Interests, Institutional, Other, Honoraria: Roche Pharma AG, Roche Pharma AG, Bristol-Myers Squibb, Boehringer Ingelheim, MSD Oncology, Novartis, Amgen, Eli Lilly, Eisai, Merck Serono, Pfizer, Takeda, Bayer, Janssen Oncology, Otsuka, PharmaMar, Sanofi. B. Mennecier: Financial Interests, Personal, Advisory Role, Consultant: Amgen. F. Bozorgmehr: Financial Interests, Personal, Other, Honoraria: Novartis, MSD, ChugaiPharma, Roche, AstraZeneca, Janssen, Amgen, Novocure; Financial Interests, Personal, Funding: BMS, AstraZeneca, Roche. M. Majem: Financial Interests, Personal and Institutional, Funding: BMS; Financial Interests, Personal, Other, Financial and non-financial support: MSD, Boehringer Ingelheim, AstraZeneca, Roche; Financial Interests, Personal, Other: Kyowa Kyrin, Pierre Fabre, Novartis, Sanofi; Non-Financial Interests, Personal, Other: Eli Lilly. M. van den Heuvel: Financial Interests, Personal and Institutional, Funding, Sponsorship or research funding: Amgen, AstraZeneca, BMS, Janssen Pharmaceutica, Stichting Treatmeds, Merck, MSD, Novartis, Pamgene, Pfizer, Roche, Roche diagnostics; Financial Interests, Personal, Other: AbbVie, AstraZeneca, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche. H. Linardou: Financial Interests, Personal, Advisory Role, Consulting: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Merck, Amgen, Boehringer Ingelheim, Pfizer, Eli Lilly; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, AbbVie, GSK, Amgen, Boehringer Ingelheim, Pfizer, Eli Lilly; Financial Interests, Personal, Expert Testimony: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Amgen, Boehringer Ingelheim, Pfizer, Eli Lilly; Financial Interests, Personal, Other, Support for meeting attendance and/or travel: Roche, Novartis, BMS, MSD, AstraZeneca, GSK, Amgen, Boehringer Ingelheim, Pfizer; Financial Interests, Personal, Advisory Board, Data Safety Monitoring Board or Advisory Board: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Amgen, Boehringer Ingelheim, Pfizer, Eli Lilly; Non-Financial Interests, Personal, Leadership Role, Leadership or fiduciary role: European Society for Medical Oncology W4O Core Committee, Hellenic Cooperative Oncology Group- President of the Scientific Committee and Member of the Board of Directors, Hellenic Foundation for Cancer Research- Member of Board of Directors, W4O-Hellas- Legal Representative Member of Board of Directors, FAIRLIFE LCC- Member of Board of Directors; Financial Interests, Personal and Institutional, Other, PI in sponsored clinical trials: Bristol Myers Squibb, Boehringer Ingelheim, Roche, AbbVie, Eli Lilly, Novartis, AstraZeneca, Amgen, PPD, Parexel ILR, Qualitis, Health Data Specialist. B. Chul-Cho: Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Personal and Institutional, Funding: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Eli Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Financial Interests, Personal, Advisory Role, Consultant: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Medpacto, Blueprint medicines, Blueprint medicines, Hanmi; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Invited Speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp., J INTS BIO. R. Roberts-Thomson: Financial Interests, Personal, Advisory Board: Novartis, Bristol Myers Squibb, Merck Sharp and Dohme, Pfizer, AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Roche, AstraZeneca, Pierre Fabre, Merck Sharp and Dohme. I. Okamoto: Financial Interests, Institutional, Research Grant: Amgen, Astellas Pharma, Novartis, AbbVie; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD Oncology, Eli Lilly, Bristol-Myers Squibb, Chugai Pharma; Financial Interests, Personal, Other: Pfizer. N. Blais: Financial Interests, Personal, Advisory Role, Consulting: Amgen, AstraZeneca, Bayer, BeiGene, BMS, EMD Serono, Ipsen, Merck, Novartis, Pfizer, Roche, Sanofi, Servier, Takeda. G. Schvartsman: Financial Interests, Personal, Advisory Role, Consulting: Amgen, Bristol-Myers Squibb, Merck, Sharp and Dome, AstraZeneca, Sanofi, Takeda, Novartis. I. Chmielewska: Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD, Roche, BMS, Takeda. M. Forster: Financial Interests, Personal and Institutional, Research Grant: CRUK, AstraZeneca, Boehringer Ingelheim, MSD, Merck; Financial Interests, Personal, Advisory Board: Transgene; Financial Interests, Personal, Advisory Role, Consulting: Achilles, Amgen, AstraZeneca, Bayer, Boxer, Bristol-Myers Squibb, Celgene, EQRx, Guardant Health, Immutep, Ixogen, Janssen, Merck, MSD, Nanobiotix, Novartis, Oxford VacMedix, PharmaMar, Pfizer, Roche, Takeda, UltraHuman. B. Stollenwerk: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. C.C. Obiozor: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. Y. Wang: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. S. Novello: Non-Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Amgen, BI, MSD, Eli Lilly, Takeda, Pfizer, Roche, Novartis, Sanofi, GSK; Financial Interests, Personal, Advisory Role: AstraZeneca, Amgen, BI, MSD, Eli Lilly, Takeda, Pfizer, Roche, Novartis, Sanofi, GSK. All other authors have declared no conflicts of interest.