Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416).

Authors

null

Priyanka Sharma

University of Kansas Medical Center, Westwood, KS

Priyanka Sharma , Eve Rodler , William E. Barlow , Julie Gralow , Shannon Leigh Huggins-Puhalla , Carey K. Anders , Lori J. Goldstein , Ursa Abigail Brown-Glaberman , Thu-Tam Huynh , Christopher Scott Szyarto , Andrew K. Godwin , Harsh B Pathak , Elizabeth M. Swisher , Marc R Radke , Kirsten M Timms , Danika L. Lew , Jieling Miao , Lajos Pusztai , Daniel F. Hayes , Gabriel N. Hortobagyi

Organizations

University of Kansas Medical Center, Westwood, KS, University of California Davis Comprehensive Cancer Center, Sacramento, CA, SWOG Statistical and Data Management Center/Fred Hutchinson Cancer Research Center, Seattle, WA, Seattle Cancer Care Alliance, Seattle, WA, University of Pittsburgh Hillman Cancer Center, Pittsburgh, PA, Duke University Cancer Center, Durham, NC, Fox Chase Cancer Center, Philadelphia, PA, University of New Mexico/New Mexico MU-NCORP, Albuquerque, NM, Kaiser Permanente NCORP/Kaiser Permanente Medical Group, Anaheim, CA, Genesee Hematology Oncology PC/Michigan CRC NCORP, Flint, MI, University of Kansas Medical Center, Kansas City, KS, University of Washington Medical Center, Seattle, WA, Myriad Genetic Laboratories, Inc., Salt Lake City, UT, Yale University, New Haven, CT, University of Michigan, Ann Arbor, MI, University of Texas MD Anderson Cancer Center, Houston, TX

Research Funding

U.S. National Institutes of Health
U.S. National Institutes of Health, AbbVie Inc

Background: PARP inhibitors(i) are effective in BRCA-mutation-associated metastatic breast cancer(MBC). However, there are no studies evaluating PARPi + platin chemotherapy in BRCA wild-type(wt) TNBC. Approximately 1/2 of BRCAwt TNBC demonstrate homologous recombination deficiency (HRD) resulting in a BRCA-like phenotype which might render them sensitive to PARPi. S1416 compared the efficacy of cisplatin plus PARPi veliparib (Vel) or placebo (P) in 3 groups of MBC: gBRCA+; BRCA-like; and non-BRCA-like. Methods: Patients (pts) with metastatic TNBC or gBRCA1/2-associated MBC, who had received < 1 line of prior therapy were treated with cisplatin (75mg/m2) plus Vel or P (300 mg po BID days 1-14), every 3 weeks. All pts underwent central gBRCA testing. A priori established multipronged biomarker panel was used to classify BRCAwt pts into BRCA-like and non-BRCA-like groups, and included myChoice HRD score, somatic BRCA1/2 mutations, BRCA1 methylation and non-BRCA1/2 HR germline mutations. Primary end-point was progression-free survival (PFS) in the three pre-defined groups; secondary end-points included objective response rate (ORR), overall survival (OS), toxicity. Results: 323/335 randomized pts were eligible for efficacy evaluation; 31% had received 1 prior chemotherapy for MBC. 248 pts were classified into the three groups: (1) 37 gBRCA+ (2) 101 BRCA-like; (3) 110 non- BRCA-like. Remaining 75 could not be classified due to missing biomarker information. In the gBRCA+ group (which reached 62% of its projected accrual), numerically better PFS was noted with Vel compared to P (HR=0.64; p=0.26) though this difference was not statistically significant. In BRCA-like group improved PFS was noted with Vel vs P (median PFS 5.7 vs 4.3 months HR=0.58; p=0.023, 1 years PFS 20% vs 7%). Numerically better OS (median OS 13.7 vs 12.1 months, HR=0.66; p=0.14) and ORR (45% vs 35%, p=0.38) were noted with Vel vs P in BRCA-like group. Non-BRCA-like group did not show benefit of veliparib for PFS (HR=0.85; p=0.43) neither did the unclassified group (HR=0.97). Grade 3/4 neutropenia (46% vs 19%) and anemia (23% vs 7%) occurred at higher frequency in Vel arm compared to P. Conclusions: Addition of Vel to cisplatin significantly improved PFS and showed a trend towards improved OS for BRCA-like advanced TNBC. Integral biomarkers used in this study identified a subgroup of BRCAwt TNBC who benefited from addition of PARPi to cisplatin; platinum plus PARPi combination should be explored further in BRCA-like TNBC. Clinical trial information: NCT02595905.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Oral Abstract Session

Session Title

Breast Cancer—Metastatic

Track

Breast Cancer

Sub Track

Triple-Negative

Clinical Trial Registration Number

NCT02595905

Citation

J Clin Oncol 38: 2020 (suppl; abstr 1001)

DOI

10.1200/JCO.2020.38.15_suppl.1001

Abstract #

1001

Abstract Disclosures