All times are listed in CEST (Central European Summer Time)
- D. Tan (Singapore, Singapore)
- H. Wakelee (Stanford, United States of America)
To view the Session Chair DOI click here
1O - Osimertinib versus gefitinib followed by osimertinib in patients with EGFR-mutant non-small cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE trial
- J. REMON MASIP (Villejuif, France)
- J. REMON MASIP (Villejuif, France)
- S. Ponce Aix (Madrid, Spain)
- A. Callejo Perez (Barcelona, Spain)
- K. Al-rabi (Amman, Jordan)
- R. Bernabe Caro (Seville, Spain)
- L. Greillier (Marseille, France)
- M. Majem Tarruella (Barcelona, Spain)
- N. Reguart Aransay (Barcelona, Spain)
- I. Monnet (Creteil, France)
- S. Cousin (Bordeaux, France)
- P. Garrido Lopez (Madrid, Spain)
- G. Robinet (Brest, France)
- R. Garcia Campelo (A Coruña, Spain)
- A. Madroszyk Flandin (Marseille, Cedex, France)
- J. Mazieres (Toulouse, France)
- H. Curcio (Caen, France)
- Y. Pretzenbacher (Brussels, Belgium)
- A. C. Dingemans (Rotterdam, Netherlands)
- R. Dziadziuszko (Gdansk, Poland)
Abstract
Background
APPLE is a 3 arms phase II non-comparative trial exploring the sequential treatment approach of gefitinib followed by osimertinib or osimertinib frontline in patients with advanced EGFR-mutant NSCLC. Here we report the exploratory analysis of the outcome with osimertinib frontline compared to a sequential approach.
Methods
Patients were randomized to: arm A (osimertinib until RECIST progression -PD-), arm B (gefitinib until the emergence of circulating tumor DNA EGFR T790M mutation or RECIST PD) or arm C (gefitinib until RECIST PD), and then switch to osimertinib in both arms B and C. In this analysis, arms B and C were pooled. Primary endpoint: Progression Free Survival rate “on osimertinib” at 18 months (PFSR-OSI-18) in arm B (H0: PFSR-OSI-18 of ≤40%). Secondary endpoints: overall survival (OS) and Brain PFS (BPFS). Primary analyses were performed in per-protocol population (PPP). In all arms, contrast-enhanced brain CT-scan was performed every 8 weeks.
Results
From 11/2017 to 02/2020, 156 patients were randomized (arm A:53, arm B/ C:103), and 136 were included in the PPP. Most patients were females (56.6% and 69.9%), with EGFR Del19 (66% and 64%). Baseline brain metastases: 19% and 29.1%, respectively. In pooled arms B/C, 70% of patients received osimertinib at PD. In arm A, PFS on osimertinib was 19.5 months. The PFSR-OSI-18 was 51.1% in Arm A and 61% in pooled arms B/C. The median OS was NR in arm A vs 42.8 (95% CI: 28.6-NR) months (mo) in pooled arm B/C, with 18-months OS of 84.4% and 82.3%, respectively. In all arms, 68 brain progression events were observed. Median time to brain PD in arm A and B/C were 34.3 mo (95% confidence interval, CI:26.9-NR) and 22.3 mo (95%CI:18.6–22.3), and corresponding hazard ratio was 0.54 (90% CI: 0.34–0.86) with 18-months BPFS of 82.2% and 63.5%, respectively.
Conclusions
In advanced EGFR mutant-NSCLC, upfront treatment with osimertinib shows a significant reduction in the risk of brain progression, with comparable OS versus the sequential treatment approach.
Clinical trial identification
NCT02856893.
Legal entity responsible for the study
EORTC.
Funding
AstraZeneca.
Disclosure
J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, MSD, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, Takeda, Sanofi; Financial Interests, Personal, Expert Testimony: OSE Immunotherapeutics; Non-Financial Interests, Personal, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Personal, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca; Non-Financial Interests, Personal, Member, Secretary of the Lung Cancer Group at the EORTC: EORTC. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Genzyme Corporation, Chugai pharmaceutical, Eisai, Inivata, Ipsen, Turning Point Therapeutics. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Eli Lilly, Pfizer, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, AbbVie, BMS, MSD, Novartis, Sanofi, Takeda, Pfizer, PharmaMar. N. Reguart Aransay: Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, Bayer, Novartis, Sanofi, Janssen, AstraZeneca, Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Boehringer Ingelheim, Guardant, BMS, Pfizer, Amgen, Novartis. I. Monnet: Other, Personal, Other, invitation to virtual ASCO 2021 and 2022: Pfizer; Other, Personal, Other, invitation to ESMO congress 2021 and 2022: Takeda. P. Garrido Lopez: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BMS, GlaxoSmithKline, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Sanofi, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Advisory Board, Spouse: Boehringer Ingelheim, Gebro, Janssen, Nordic; Financial Interests, Personal, Invited Speaker, Spouse: Boehringer Ingelheim, Janssen; Financial Interests, Personal, Other, Data monitoring committee for INC280I12201 trial in 2020: Novartis; Financial Interests, Personal, Invited Speaker, CACZ885V2201C_CANOPY-N trial: Novartis; Financial Interests, Personal, Other, Lung Cancer Medical Education TASC Committee 2021: Janssen; Financial Interests, Institutional, Invited Speaker: Novartis, Janssen, AstraZeneca, Pfizer, Blue print, Apollomics, Amgen, Array Biopharma; Financial Interests, Personal, Invited Speaker, IO102-012/KN-764 trial: IO Biotech; Financial Interests, Personal, Invited Speaker, JNJ-61186372 (JNJ-372) Clinical Development Program: Janssen; Non-Financial Interests, Personal, Leadership Role, Council member as Women for Oncology Committee ChairFellowship and Award Committee and Press CommitteeFaculty for lung and other thoracic tumours: ESMO; Non-Financial Interests, Personal, Leadership Role, President of the Spanish Federation of Medical Societies (FACME) 2020-2022Past President 2023-2024: FACME; Non-Financial Interests, Personal, Leadership Role, Former President of Spanish Medical Oncology Society: SEOM; Non-Financial Interests, Personal, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (AECC) and also Board member: AECC; Non-Financial Interests, Personal, Leadership Role, IASLC Women in Thoracic Oncology Working Group Member: IASLC; Non-Financial Interests, Personal, Advisory Role, Member of the Spanish National Health Advisory Board: Spanish Minister of Health; Non-Financial Interests, Personal, Advisory Role, Assessment for lung cancer screening evaluation: EUnetHTA; Non-Financial Interests, Personal, Advisory Role: Spanish National Evaluation network (RedETS); Non-Financial Interests, Personal, Advisory Role, scientific advisory group member for clinical immunological, oncology and lung cancer areas: EMA; Other, Personal, Other, My son is working in the pharma company TEVA as an engineer. I do not have any kind of relationship with TEVA: TEVA. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Sanofi, Amgen, Bayer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Takeda, Eli Lilly, Janssen, Pfizer, AstraZeneca, Eli Lilly, Amgen, Daiichi Sankyo, Roche, Roche, JNJ, Mirati; Financial Interests, Institutional, Research Grant: Amgen; Non-Financial Interests, Personal, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Personal, Member: IASCL, ASCO, AACR. All other authors have declared no conflicts of interest.
2O - Phase II randomized study of osimertinib (OSI) with or without local consolidative therapy (LCT) for metastatic EGFR mutant non-small cell lung cancer (NSCLC): Analysis of adverse events (AEs)
- S. J. Ghandi (Houston, United States of America)
- S. J. Ghandi (Houston, United States of America)
- M. B. Antonoff (Houston, United States of America)
- G. Blumenschein Jr. (Houston, United States of America)
- Z. Liao (Houston, United States of America)
- D. R. Gomez (New York, United States of America)
- J. Y. Chang (Houston, United States of America)
- S. H. Lin (Houston, United States of America)
- T. Cascone (Houston, United States of America)
- C. Gay (Houston, United States of America)
- J. Tu (Houston, United States of America)
- X. Le (Houston, United States of America)
- A. Tsao (Houston, United States of America)
- M. S. O’Reilly (Houston, United States of America)
- M. S. Ning (Houston, United States of America)
- C. Blakley (San Francisco, United States of America)
- C. G. Rusthoven (Denver, United States of America)
- A. A. Vaporciyan (Houston, United States of America)
- S. G. Swisher (Houston, United States of America)
- J. V. Heymach (Houston, United States of America)
- Y. Y. Elamin (Houston, United States of America)
Abstract
Background
Most patients with EGFR mutant NSCLC who have an initial response to OSI exhibit persistent residual disease that may enable emergence of acquired resistance. Eliminating residual disease with LCT may delay resistance and improve clinical outcomes. Safety of OSI with LCT, however, is not well defined. Here we report safety data from a multicenter randomized phase II study of OSI with or without LCT for patients with EGFR mutant NSCLC.
Methods
Metastatic NSCLC patients with tyrosine kinase inhibitor naïve EGFR mutation (L858R/Exon 19 deletion) or T790M resistance mutation after prior therapy received 6–12 weeks of induction OSI. Patients without progression per RECIST 1.1 were randomized to OSI alone vs LCT plus OSI until progression. Primary objective was progression free survival. Secondary objective was safety. Patients were evaluated every 8 weeks using CTCAE v4.0. All possible, probable, and definite treatment related AEs were analyzed.
Results
From 2018 to 2022, 122 patients (median age: 65, range: 30–88) were randomized (63 to OSI alone; 59 to OSI plus LCT). Among 59 patients who received LCT, 35 (59%) received RT alone, 17 (29%) received surgery alone, and 7 (12%) received both RT and surgery. At median follow up of 16 months (range: 2–49), there were no grade 4/5 AEs. There was no significant difference in grade 3 AEs between OSI alone and OSI plus LCT (16% vs 29%; p = 0.08). The most common grade 3 AEs with OSI alone were hyponatremia (4.8%), transaminitis (4.8%), and pneumonitis (3.4%). The most common grade 3 AEs with OSI plus LCT were hyponatremia (6.8%), diarrhea (3.4%), empyema (3.4%), and pneumonitis (1.7%). Among 42 patients that received RT, 1 (2%) had a grade 3 AE possibly related to RT (non-cardiac chest pain). Among 24 surgical patients, 3 (13%) had surgery related grade 3 AEs (1 arterial injury, 2 empyema). Common grade 1–2 AEs with OSI plus LCT were fatigue (56%), diarrhea (45%), dyspnea (31%), cough (29%), pneumonitis (10%), dysphagia (12%), and esophagitis (7%).
Conclusions
OSI plus LCT is well tolerated in EGFR mutated metastatic NSCLC patients without significant increase in serious AEs compared to OSI alone.
Clinical trial identification
NCT03410043.
Legal entity responsible for the study
The University of Texas MD Anderson Cancer Center.
Funding
National Comprehensive Cancer Network (NCCN).
Disclosure
S.J. Gandhi: Financial Interests, Institutional, Research Grant: Nanobiotix Inc, BMS, Gateway Foundation.
Invited Discussant 1O and 2O
- D. Tan (Singapore, Singapore)
- D. Tan (Singapore, Singapore)
Q&A
- D. Tan (Singapore, Singapore)
- D. Tan (Singapore, Singapore)
3O - Long-term efficacy, safety, and predictors of response to amivantamab among patients with post-platinum EGFR Ex20ins-mutated advanced NSCLC
- P. Garrido Lopez (Madrid, Spain)
- P. Garrido Lopez (Madrid, Spain)
- N. Girard (Paris, France)
- B. Cho (Seoul, Korea, Republic of)
- J. Sabari (New York, United States of America)
- A. Spira (Fairfax, United States of America)
- R. E. Sanborn (Portland, United States of America)
- K. Goto (Kashiwa, Japan)
- J. Yang (Taipei City, Taiwan)
- J. Curtin (Spring House, United States of America)
- X. Lyu (Shanghai, China)
- A. He (Horsham, United States of America)
- J. Penton (High Wycombe, United Kingdom)
- J. Edwards (High Wycombe, United Kingdom)
- G. Low Massin (Singapore, Singapore)
- K. Xia (Spring House, United States of America)
- M. Chioda (Spring House, United States of America)
- M. Thayu (Spring House, United States of America)
- R. E. Knoblauch (Spring House, United States of America)
- P. Mahadevia (Spring House, United States of America)
- N. Leighl (Toronto, Canada)
Abstract
Background
Amivantamab (ami), an EGFR and MET bispecific antibody with immune cell-directing activity, is approved to treat patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations (Ex20ins) who progressed on prior platinum-based chemotherapy. This report presents long-term results for this population.
Methods
Pts with EGFR Ex20ins advanced NSCLC whose disease progressed on platinum-based chemotherapy were recruited in CHRYSALIS. Pts who received the approved phase II dose of 1050 mg (1400 mg, ≥80 kg) by 08 Jun 2020 were included. Response was assessed by investigator per RECIST v1.1.
Results
As of Sep 2022, among 114 pts included, the median follow-up was 19.2 months and 48 (42%) pts alive. Investigator-assessed overall response rate (ORR) was 37% (95% CI, 28–46), with median duration of response of 12.5 months (95% CI, 6.9–19.3), median progression-free survival of 6.9 months (95% CI, 5.6–8.8), and median overall survival of 23 months (95% CI, 18.5–29.5). Activity was observed across subgroups, including the elderly (ORR of 32% and 33% for age ≥65 and ≥75, respectively), heavily pretreated pts (ORR of 53% for >2 prior lines, 42% for prior immunotherapy, and 52% for prior EGFR TKI therapy), or those sensitive or resistant to prior platinum-based chemotherapy (ORR of 36% and 31%, respectively). No new safety signals were detected, with rash (all grades, 89%) and infusion-related reactions (67%) remaining the most frequent toxicities. There are 48 (42%) pts on ami for ≥12 (28-day) cycles. Treatment is ongoing in 15 (13%) pts (11 responders and 4 with stable disease as best response) who have received ami for a median of 2.6 years. An analysis comparing pts without and with sustained clinical benefit (≥12 cycles on ami) will presented at the meeting, including plasma ctDNA data.
Conclusions
Ami demonstrated robust efficacy that was consistently observed across post-platinum patients with EGFR Ex20ins NSCLC, including the elderly, those with multiple prior lines, or those who were platinum sensitive or refractory. A subgroup derived long-term benefit; the mechanisms for which will be explored further.
Clinical trial identification
NCT02609776.
Editorial acknowledgement
Medical writing support was provided by Lumanity Communications, Inc.
Legal entity responsible for the study
The authors.
Funding
Janssen.
Disclosure
P. Garrido Lopez: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BMS, GlaxoSmithKline, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Sanofi, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Advisory Board, Spouse: Boehringer Ingelheim, Gebro, Janssen, Nordic; Financial Interests, Personal, Invited Speaker, Spouse: Boehringer Ingelheim, Janssen; Financial Interests, Personal, Other, Data monitoring committee for INC280I12201 trial in 2020: Novartis; Financial Interests, Personal, Invited Speaker, CACZ885V2201C_CANOPY-N trial: Novartis; Financial Interests, Personal, Other, Lung Cancer Medical Education TASC Committee 2021: Janssen; Financial Interests, Institutional, Invited Speaker: Novartis, Janssen, AstraZeneca, Pfizer, Blue Print, Apollomics, Amgen, Array Biopharma; Financial Interests, Personal, Invited Speaker, IO102-012/KN-764 trial: IO Biotech; Financial Interests, Personal, Invited Speaker, JNJ-61186372 (JNJ-372) Clinical Development Program: Janssen; Non-Financial Interests, Personal, Leadership Role, Council member as Women for Oncology Committee Chair Fellowship and Award Committee and Press Committee Faculty for lung and other thoracic tumours: ESMO; Non-Financial Interests, Personal, Leadership Role, President of the Spanish Federation of Medical Societies (FACME) 2020–2022Past President 2023–2024: FACME; Non-Financial Interests, Personal, Leadership Role, Former President of Spanish Medical Oncology Society: SEOM; Non-Financial Interests, Personal, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (AECC) and also Board member: AECC; Non-Financial Interests, Personal, Leadership Role, IASLC Women in Thoracic Oncology Working Group Member: IASLC; Non-Financial Interests, Personal, Advisory Role, Member of the Spanish National Health Advisory Board: Spanish Minister of Health; Non-Financial Interests, Personal, Advisory Role, Assessment for lung cancer screening evaluation: EUnetHTA; Non-Financial Interests, Personal, Advisory Role: Spanish National Evaluation network (RedETS); Non-Financial Interests, Personal, Advisory Role, scientific advisory group member for clinical immunological, oncology and lung cancer areas: EMA; Other, Personal, Other, My son is working in the pharma company TEVA as an engineer. I do not have any kind of relationship with TEVA: TEVA. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Personal, Other, Family member is an employee: AstraZeneca. B.C. Cho: Financial Interests, Personal, Other, Consulting role: 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, Janssen; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Invited Speaker: Interpark Bio Convergence Corp., J INTS BIO; 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, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: 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; Other, Personal, Other, Founder: DAAN Biotherapeutics. J. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Mirati Therapeutics. A. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines; Financial Interests, Personal, Other, Consulting or Advisory Role/Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol-Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Invited Speaker: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mersana, Mirati Therapeutics, Rubius, Synthekine, Blueprint Medicines. R.E. Sanborn: Financial Interests, Personal, Advisory Board: AstraZeneca, EMD Serono, Daiichi Sankyo, Eli Lilly, Janssen Oncology, Macrogenics, Sanofi Aventis, Regeneron, Mirati Therapeutics, GlaxoSmithKline; Financial Interests, Personal, Invited Speaker: Amgen, GlaxoSmithKline, Janssen Oncology; Financial Interests, Institutional, Funding, Funding for investigator-sponsored trial: Merck, AstraZeneca; Financial Interests, Institutional, Other, Institutional research support: BMS; Financial Interests, Institutional, Funding, Clinical trial funding: Jounce. K. Goto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Amoy Diagnosties Co.,Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Guardant Health Inc., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K., Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K.; Financial Interests, Personal, Expert Testimony: Medpace Japan K.K.; Financial Interests, Personal and Institutional, Funding: Amgen Inc., Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ignyta,Inc., Janssen Pharmaceutical K.K., Kissei Pharmaceutical CO., LTD., Kyowa Kirin Co., Ltd., Loxo Oncology, Inc., Medical & Biological Laboratories CO., LTD., Merck Biopharma Co., Ltd., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sumitomo Dainippon Pharma Co., Ltd., Spectrum Pharmaceuticals, Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics,Inc., Amgen Astellas BioPharma K.K., Bayer Yakuhin, Ltd., Blueprint Medicines Corporation., Life Technologies Japan Ltd., NEC Corporation., Novartis Pharma K.K.; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. J. Curtin: Financial Interests, Personal, Full or part-time Employment: Janssen R&D; Financial Interests, Personal, Stocks/Shares: Janssen R&D. X. Lyu: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. A. He: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. J. Penton: Financial Interests, Personal, Full or part-time Employment: Janssen R&D; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. J. Edwards: Financial Interests, Personal, Full or part-time Employment: Janssen-Cilag Ltd, Novartis Pharmaceuticals UK Ltd; Financial Interests, Personal, Stocks/Shares: AstraZeneca. G. Low Massin: Financial Interests, Personal, Full or part-time Employment: Janssen R&D; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. K. Xia: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. M. Chioda: Financial Interests, Personal, Full or part-time Employment: Janssen R&D; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. M. Thayu: Financial Interests, Personal, Full or part-time Employment: Janssen R&D; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment: Janssen R&D; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. P. Mahadevia: Financial Interests, Personal, Full or part-time Employment: Janssen R&D; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Eli Lilly, MSD, Pfizer, Roche, Takeda. All other authors have declared no conflicts of interest.
4O - Patient-reported outcomes from the CodeBreaK 200 phase III trial comparing sotorasib versus docetaxel in KRAS G12C-mutated NSCLC
- D. M. Waterhouse (Boston, United States of America)
- D. M. Waterhouse (Boston, United States of America)
- S. Rothschild (Basel, Switzerland)
- C. Dooms (Leuven, Belgium)
- B. Mennecier (Strasbourg, France)
- F. Bozorgmehr (Heidelberg, Germany)
- M. Majem Tarruella (Barcelona, Spain)
- M. Van den Heuvel (Nijmegen, Netherlands)
- H. Linardou (Athens, Greece)
- B. Chul-Cho (Seoul, Korea, Republic of)
- R. Roberts-Thomson (Woodville, Australia)
- I. Okamoto (Fukuoka, Japan)
- N. Blais (Montreal, Canada)
- G. Schvartsman (São Paulo, Brazil)
- K. Holmskov (Odense, Denmark)
- I. Chmielewska (Lublin, Poland)
- M. Forster (London, United Kingdom)
- B. Stollenwerk (Rotkreuz, Switzerland)
- C. C. Obiozor (Thousand Oaks, United States of America)
- Y. Wang (Thousand Oaks, United States of America)
- S. Novello (Orbassano, Italy)
Abstract
Background
In the CodeBreaK 200 phase III trial, sotorasib significantly improved PFS (primary endpoint) versus docetaxel in previously treated KRASG12C-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, KRASG12C-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.
Invited Discussant 3O and 4O
- J. Naidoo (Dublin, Ireland)
- J. Naidoo (Dublin, Ireland)
Q&A
- H. Wakelee (Stanford, United States of America)
- H. Wakelee (Stanford, United States of America)