Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair–Deficient/Microsatellite Instability–High Metastatic Colorectal Cancer
Michael J. OvermanMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchSara LonardiMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchKa Yeung Mark WongMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchHeinz‐Josef LenzMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchFabio GelsominoMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchMassimo AgliettaMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchMichael A. MorseMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchEric Van CutsemMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchRay McDermottMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchAndrew HillMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchMichael B. SawyerMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchAlain HendliszMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchBart NeynsMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchMagali SvrcekMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchRebecca A. MossMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchJean-Marie LedeineMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchZ. Alexander CaoMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchShital KambleMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchScott KopetzMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology ResearchThierry AndréMichael J. Overman and Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX; Sara Lonardi, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova; Fabio Gelsomino, University Hospital of Modena, Modena; Massimo Aglietta, Institute for Cancer Research and Treatment of Candiolo, University of Torino Medical School, Turin, Italy; Ka Yeung Mark Wong, Sydney Medical School, University of Sydney, Sydney, New South Wales; Andrew Hill, Tasman Oncology Research
2018en
ABI
Аннотация
Purpose Nivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported. Patients and Methods Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR. Results Of 119 patients, 76% had received ≥ two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reached; most responses (94%) were ongoing at data cutoff. Progression-free survival rates were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%. Statistically significant and clinically meaningful improvements were observed in patient-reported outcomes, including functioning, symptoms, and quality of life. Grade 3 to 4 treatment-related adverse events (AEs) occurred in 32% of patients and were manageable. Patients (13%) who discontinued treatment because of study drug-related AEs had an ORR (63%) consistent with that of the overall population. Conclusion Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC.
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