Hope S. Rugo, MD, Professor, Department of Medicine (Hematology/Oncology); and Director, Breast Oncology and Clinical Trials Education, UCSF Helen Dillard Family Comprehensive Cancer Center speaks about ESMO 2021 Abstract – #LBA16, Proffered Paper: Final Results of KEYNOTE-355: A Randomized, Double-Blind, Phase 3 Study of Pembrolizumab + Chemotherapy vs Placebo + Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer (TNBC).
LBA16 Abstract:
Background:
In a previous interim analysis of KEYNOTE-355 (NCT02819518), patients (pts) with metastatic TNBC whose tumors expressed PD-L1 (CPS 10) saw a substantial improvement in PFS compared to placebo (pbo) + chemo (HR, 0.65, 95 percent CI, 0.49"“0.86; one-sided P=0.0012 [P-value threshold, 0.00411]). The final findings for the dual primary endpoint of OS as well as other research endpoints are presented.
Methods:
For up to 35 administrations of pembro/pbo or until progression/intolerable toxicity, 847 patients with de novo metastases or a 6-month DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin) or pbo + chemo. Prior (neo)adjuvant therapy with same-class chemo was stratified by chemo type (taxane or gemcitabine-carboplatin), PD-L1 status (CPS 1 or 1), and PD-L1 status (CPS 1 or 1). (yes or no). PFS (RECIST v1.1 by BICR) and OS in patients with PD-L1+ tumors (CPS 10 and 1) and all patients are the main objectives (ITT). ORR is a supplementary metric. AEs were tracked and graded according to the NCI CTCAE v4.0.
Results:
The median follow-up was 44.1 months as of June 15, 2021. In patients with CPS 10 tumors, pembro with chemo substantially increased OS vs to chemo alone (Table). The p-value threshold for a substantial OS advantage of pembro + chemo in patients with CPS 1 tumors was not satisfied, thus no formal ITT testing was done. The advantage of pembro + chemo on PFS was similar to previous findings. In patients with CPS 10 tumors, pembro with chemo enhanced ORR. With PD-L1 enrichment, the pembro treatment effect increased for all endpoints. The rate of grade 3-5 treatment-related AEs was 68.1 percent with pembro + chemo (2 fatalities) vs 66.9% with chemo alone (0 deaths).
Conclusions:
In patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 (CPS 10) who received Pembro + chemo, there was a statistically significant and clinically relevant improvement in OS compared to chemo alone. There were no new safety signals discovered.
Clinical trial identification
NCT02819518.