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Abstract GS1-02: Final results of KEYNOTE-355: Randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer

2022; American Association for Cancer Research; Volume: 82; Issue: 4_Supplement Linguagem: Inglês

10.1158/1538-7445.sabcs21-gs1-02

1538-7445

Javier Cortés, David W. Cescon, Hope S. Rugo, Zbigniew Nowecki, Seock‐Ah Im, Mastura Md Yusof, Carlos Gallardo, O. N. Lipatov, Carlos H. Barrios, Jose Manuel Perez‐García, Hiroji Iwata, Norikazu Masuda, Marco Torregroza Otero, Erhan Gökmen, Sherene Loi, Zifang Guo, Xuan Zhou, Vassiliki Karantza, Wilbur Pan, Peter Schmid,

Cancer Immunotherapy and Biomarkers

Abstract Background: In the phase 3 KEYNOTE-355 trial (NCT02819518), pembrolizumab (pembro) combined with chemotherapy (chemo) showed statistically significant improvements in OS and PFS compared to placebo + chemo in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 with a combined positive score (CPS) ≥10. There were no statistically significant differences between treatment groups in the CPS ≥1 population, and statistical significance was not tested in the ITT population due to the prespecified testing strategy. Here, we compare outcomes in subgroups of patients by additional CPS cut-offs to the primary results of KEYNOTE-355. Methods: 847 patients with measurable disease per RECIST v1.1, ECOG PS 0-1, and ≥6 month disease-free interval were randomized 2:1 to pembro + chemo (nab-paclitaxel 100 mg/m2 days 1, 8, and 15 every 28 days; paclitaxel 90 mg/m2 days 1, 8, and 15 every 28 days; or gemcitabine 1000 mg/m2 + carboplatin AUC 2 days 1 and 8 every 21 days) or placebo + chemo for up to 35 administrations of pembro/placebo or until progression/intolerable toxicity. Patients were stratified by chemo type (taxane or gemcitabine-carboplatin), PD-L1 status (CPS ≥1 or <1), and prior neoadjuvant/adjuvant treatment with same-class chemo (yes or no). Dual primary endpoints were OS and PFS (RECIST v1.1, blinded independent central review) in patients with PD-L1-positive tumors (CPS ≥10 and ≥1) and in the ITT population. Hazard ratios (HRs) and 95% CIs in the additional CPS subgroups were based on an unstratified Cox model. Results: At the time of the final analysis (data cutoff, June 15, 2021), the median time from randomization to data cutoff was 44 months. Baseline characteristics of the CPS 1-9, 10-19, and ≥20 subgroups were generally similar to those of the ITT population. In the primary analyses, the HRs (95% CI) for OS were 0.73 (0.55-0.95) in the CPS ≥10 subgroup, 0.86 (0.72-1.04) in the CPS ≥1 subgroup, and 0.89 (0.76-1.05) in the ITT population; HRs (95% CI) for PFS were 0.66 (0.50-0.88), 0.75 (0.62-0.91), and 0.82 (0.70-0.98), respectively. Efficacy data are presented for the additional CPS subgroups in the Table. For OS, results in the CPS 1-9 subgroup showed comparable efficacy for pembro + chemo and placebo + chemo; however, results in the CPS 10-19 and CPS ≥20 subgroups showed a similar treatment benefit with the addition of pembro. Results for PFS were generally consistent with those observed for OS. Conclusions: These results provide support that CPS ≥10 is a reasonable cut-off to define the population of patients with metastatic TNBC expected to derive treatment benefit from pembro + chemo. Table. Efficacy in additional subgroups of patients by PD-L1 CPSCPS subgroupTreatmentMedian OS, mo (95% CI)OS HR (95% CI)*Median PFS, mo (95% CI)PFS HR (95% CI)*1-9†Pembro + Chemo. n = 20513.9. (12.2-16.6)1.09 (0.85-1.40)5.7. (5.4-7.4)0.85 (0.65-1.11)Placebo + Chemo n = 10815.5. (12.4-17.6)5.6. (5.3-7.6)10-19†Pembro + Chemo. n = 8020.3. (15.2-29.0)0.71 (0.46-1.09)9.9. (7.4-11.8)0.70 (0.44-1.09)Placebo + Chemo n = 3917.6. (10.3-25.8)7.6. (5.3-9.7)≥20‡Pembro + Chemo. n = 14024.0 (19.0-28.3)0.72 (0.51-1.01)9.2 (7.6-11.8)0.62 (0.44-0.88)Placebo + Chemo n = 6415.6. (12.3-20.8)5.4 (3.9-7.2)*Analyses based on an unstratified Cox model. †Post-hoc analyses. ‡Prespecified exploratory analyses. Citation Format: Javier Cortes, David W. Cescon, Hope S. Rugo, Zbigniew Nowecki, Seock-Ah Im, Mastura Md Yusof, Carlos Gallardo, Oleg Lipatov, Carlos Henrique Barrios, Jose Perez-Garcia, Hiroji Iwata, Norikazu Masuda, Marco Torregroza Otero, Erhan Gokmen, Sherene Loi, Zifang Guo, Xuan Zhou, Vassiliki Karantza, Wilbur Pan, Peter Schmid. Final results of KEYNOTE-355: Randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS1-02.