دورية أكاديمية
Standard-Dose Pembrolizumab Plus Alternate-Dose Ipilimumab in Advanced Melanoma: KEYNOTE-029 Cohort 1C, a Phase 2 Randomized Study of Two Dosing Schedules
| العنوان: | Standard-Dose Pembrolizumab Plus Alternate-Dose Ipilimumab in Advanced Melanoma: KEYNOTE-029 Cohort 1C, a Phase 2 Randomized Study of Two Dosing Schedules |
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| المؤلفون: | Long, Georgina, Robert, Caroline, Butler, Marcus, Couture, Felix, Carlino, Matteo, O'Day, Steven, Atkinson, Victoria, Cebon, Jonathan, Brown, Michael, Dalle, Stéphane, Hill, Andrew, Gibney, Geoffrey, Mccune, Steven, Menzies, Alexander, Niu, Cuizhen, Ibrahim, Nageatte, Moreno, Blanca Homet, Diab, Adi |
| المساهمون: | Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard Lyon |
| المصدر: | ISSN: 1078-0432. |
| بيانات النشر: | HAL CCSD American Association for Cancer Research |
| سنة النشر: | 2021 |
| المجموعة: | HAL Lyon 1 (University Claude Bernard Lyon 1) |
| مصطلحات موضوعية: | [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | International audience ; Abstract Purpose: Standard-dose pembrolizumab plus alternative-dose ipilimumab (1 mg/kg Q3W for 4 doses) were tolerable and had robust antitumor activity in advanced melanoma in cohort B of the phase 1 KEYNOTE-029 study. Cohort C evaluated standard-dose pembrolizumab with two other alternative ipilimumab regimens. Patients and Methods: Patients with treatment-naive unresectable stage III/IV melanoma were randomly assigned 1:1 to pembrolizumab 200 mg Q3W for ≤24 months plus ipilimumab 50 mg Q6W for 4 doses (PEM200+IPI50), or the same pembrolizumab regimen plus ipilimumab 100 mg Q12W for 4 doses (PEM200+IPI100). Primary end points were incidence of grade 3–5 treatment-related adverse events (TRAE) and objective response rate (ORR) per RECIST v1.1 by independent central review. Per protocol-defined thresholds, grade 3–5 TRAE incidence ≤26% indicated meaningful toxicity reduction and ORR ≥48% indicated no decrease in efficacy versus data reported for other PD-1 inhibitor/ipilimumab combinations. Results: Median follow-up on February 18, 2019, was 16.3 months in PEM200+IPI50 (N = 51) and 16.4 months in PEM200+IPI100 (N = 51). Grade 3–5 TRAEs occurred in 12 (24%) patients in PEM200+IPI50 and 20 (39%) in PEM200+IPI100. One patient in PEM200+IPI50 died from treatment-related autoimmune myocarditis. Immune-mediated AEs or infusion reactions occurred in 21 (42%) patients in PEM200+IPI50 and 28 (55%) in PEM200+IPI100. ORR was 55% in PEM200+IPI50; 61% in PEM200+IPI100. Conclusions: Pembrolizumab 200 mg Q3W plus ipilimumab 50 mg Q6W or 100 mg Q12W demonstrated antitumor activity above the predefined threshold; pembrolizumab plus ipilimumab 50 mg Q6W had lower incidence of grade 3–5 TRAEs than the predefined threshold, suggesting a reduction in toxicity. See related commentary by Jameson-Lee and Luke, p. 5153 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-04065982; https://hal.science/hal-04065982Test |
| DOI: | 10.1158/1078-0432.CCR-21-0793 |
| الإتاحة: | https://doi.org/10.1158/1078-0432.CCR-21-0793Test https://hal.science/hal-04065982Test |
| رقم الانضمام: | edsbas.D61BF3EA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1158/1078-0432.CCR-21-0793 |
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