University of Pittsburgh Medical Center, Division of Hematology Oncology, Pittsburgh, PA
Adam Brufsky , Sung-Bae Kim , Zanete Zvirbule , Luc Yves Dirix , Alexandru E. Eniu , Francisco Carabantes , Yann Izarzugaza , Jeroen Mebis , Joohyuk Sohn , Matthew Wongchenko , Saibah Chohan , Reena Amin , V. A. McNally , David Miles , Sherene Loi
Background: COLET showed that the addition of C (MEK1/2 inhibitor) to P resulted in an increased ORR (38%; Brufsky, SABCS 2017); IMpassion130 demonstrated clinical benefit with the combination of PD-L1 inhibitor A and nP as 1L tx for pts with mTNBC (Schmid, N Engl J Med, 2018). We investigated the efficacy and safety of A + C + P/nP in pts with mTNBC, as this combination may target multiple cancer immune escape mechanisms simultaneously. Methods: In the multi-stage, multi-cohort Phase II COLET study, pts with histologically confirmed mTNBC were randomized 1:1 to receive 1L tx with A 840 mg IV (d1, d15) + C 60 mg qd (d3-d23) + P 80 mg/m2 IV (d1, d8, d15; cohort 2) or + nP 100 mg/m2 (d1, d8, d15; cohort 3) in 28-day cycles until progression or toxicity. The primary endpoint (EP) was confirmed ORR per investigator-assessed RECIST 1.1. Additional EPs were DOR, PFS, OS, safety and exploratory efficacy by PD-L1 status. Results: As of 10 Aug 2018 (6.5-mo median follow-up), 63 and 62 pts were evaluable for efficacy and safety, respectively. In cohorts 2 and 3, 21 pts (66%) and 20 pts (65%) had received neo/adjuvant taxane tx, 9 pts (28%) and 6 pts (19%) had a disease-free interval of ≤12 mo, respectively. All pts had ≥1 AE; 69% and 70% had Gr 3-5 AEs and 47% and 43% had serious AEs in cohorts 2 and 3, respectively. Efficacy data for all pts and by PD-L1 expression on tumor-infiltrating immune cells (IC ≥1%; PD-L1+) are summarized in the Table. Conclusions: ORRs were similar between the A + C + P arm and A + C + nP arm. Numerically higher ORR and PFS were observed in pts with PD-L1+ disease. The combination’s safety profile was consistent with the known individual safety profiles, and A did not increase toxicity. Clinical trial information: NCT02322814
A + C + P | A + C + nP | |||||
---|---|---|---|---|---|---|
All Ptsa (n=32) | PD-L1+ (n=16) | PD-L1− (n=9) | All Ptsb,c (n=31) | PD-L1+ (n=15) | PD-L1− (n=11) | |
Confirmed ORR, n (%) | 11 (34) | 7 (44) | 1 (11) | 9 (29) | 5 (33) | 3 (27) |
CR | 2 (6) | 1 (6) | 0 | 0 | 0 | 0 |
PR | 9 (28) | 6 (38) | 1 (11) | 9 (29) | 5 (33) | 3 (27) |
SD, n (%) | 11 (34) | 3 (19) | 5 (56) | 16 (52) | 9 (60) | 5 (45) |
PD, n (%) | 10 (31) | 6 (38) | 3 (33) | 3 (10) | 0 | 2 (18) |
6-mo PFS rate, % | 40.5 | 55.6 | 20.0 | 50.1 | 55.3 | 46.0 |
6-mo OS rate, % | 84.1 | 85.6 | 75.0 | 90.0 | 86.7 | 90.1 |
a 7 pts and b 5 pts with unknown PD-L1 status. c 3 pts not evaluable.
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