Project Description

Oral Abstract Presentation
Selected by the 2020 Annual Meeting Scientific Program Committee
Type: Oral Abstract Presentation
Presenter: Nadine Tung, MD
Presented: May 29, 2020
Abstract ref: 1002
Subtitles/Captions:

Authors: Nadine M. Tung, Mark E. Robson, Steffen Ventz, Cesar Augusto Santa-Maria, Paul Kelly Marcom, Rita Nanda, Payal D Shah, Tarah Jean Ballinger, Eddy Shih-Hsin Yang, Michelle E. Melisko, Adam Brufsky, Shaveta Vinayak, Michelle Demeo, Colby Jenkins, Susan M. Domchek, Gerburg M. Wulf, Ian E. Krop, Antonio C. Wolff, Eric P. Winer, Judy Ellen Garber, Translational Breast Cancer Research Consortium; Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute, Boston, MA; Memorial Sloan Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Brookline, MA; Northwestern University Feinberg School of Medicine, Chicago, IL; Duke University Medical Center, Durham, NC; The University of Chicago, Chicago, IL; University of Pennsylvania, Philadelphia, PA; Indiana University, Indianapolis, IN; University of Alabama at Birmingham, Birmingham, AL; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Pittsburgh Medical Center, Division of Hematology Oncology, Pittsburgh, PA; University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH; Dana-Farber Cancer Institute, Boston, MA; Beth Israel Deaconess Medcl Ctr, Boston, MA; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA

Abstract Disclosures

Research Funding: Astra-Zeneca

Background: Olaparib, a PARP inhibitor, is approved for HER2-negative MBC in gBRCA1/2 mutation carriers. Olaparib Expanded, an investigator-initiated study, assessed the response to olaparib in MBC patients with sBRCA1/2 mutations or g/s mutations in DDR-pathway genes other than BRCA1/2.

Methods: Eligibility included: MBC with measurable disease; progression on < 2 metastatic chemotherapy regimens. Prior PARP inhibitor or progression on platinum was not allowed. Cohort 1 included patients with germline mutations in non-BRCA1/2 DDR-pathway genes. In Cohort 2 were those with somatic mutations in these genes or BRCA1/2; germline testing was required only to exclude a gBRCA mutation if a sBRCA mutation was present. Patients received olaparib 300 mg bid until progression or unacceptable toxicity. For each cohort, a single-arm Simon two-stage design was used with 13 then 14 patients in the 1st and 2nd stages, respectively. The null hypothesis within each cohort [≤ 5% objective response rate (ORR)] would be rejected if > 4 responses were seen at the end of stage 2. Secondary endpoints include clinical benefit rate, progression-free survival, and duration of response.

Results: 54 patients enrolled from March 2018 to Jan 2020; 1 ineligible sBRCA2 was excluded. Median age was 59 yrs (range: 30-87). 40 patients had ER+ HER2-, 3 HER2+, and 10 TNBC. 87% had a mutation in PALB2, sBRCA1/2, ATM or CHEK2. ORR was 29.6% (8/27, 90%-CI: 15.6%-47.1%) in Cohort 1 and 38.5% (10/26, 90%-CI: 22.5%-56.4%) in Cohort 2. Responses were gene specific (Table): gPALB2 and sBRCA mutations predicted response; no responses were seen with only a CHEK2 or ATM mutation. To date, responses as long as 16.4 months have been observed. Responses were seen in all subtypes: 5/10 TNBC, 1/3 HER2+, 12/40 ER+ HER2-. 11 responses occurred after prior CDK4/6 inhibitor. In June 2020, final data for confirmed ORR and secondary endpoints will be reported.

Conclusions: In this proof-of-principle study, single-agent olaparib successfully met its primary endpoint in both cohorts. Activity was seen largely in patients with MBC and sBRCA1/2 or gPALB2 mutations but not with ATM or CHEK2 mutations. Clinical trial information: NCT03344965.

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Oral Abstract Presentation
Selected by the 2020 Annual Meeting Scientific Program Committee
Type: Oral Abstract Presentation
Presenter: Nadine Tung, MD
Presented: May 29, 2020
Abstract ref: 1002
Subtitles/Captions: