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ASCO 2021 | OlympiA: adjuvant olaparib in gBRCAm, HER2-negative, high-risk, early breast cancer
Erika Hamilton, MD, Sarah Cannon Research Institute, Nashville, TN, speaks on the findings of OlympiA (NCT02032823), a randomized, double-blind, Phase III trial evaluating adjuvant olaparib after neoadjuvant chemotherapy in patients with germline BRCA1/2 mutations (gBRCAm) and high-risk HER2-negative early breast cancer. Adjuvant olaparib resulted in a significantly improved invasive disease-free survival and distant disease free-survival with acceptable toxicity. Dr Hamilton concludes by addressing the implications of this study, including increased access to coverage for BRCA testing. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.
Transcript (edited for clarity)
From OlympiAD and EMBRACA of the benefit of PARP inhibitors for metastatic breast cancer that has BRCA alterations. In this study OlympiA, looked at this in the adjuvant setting. So, it was high risk patients that were HER2-negative. And there were a few categories you could fall into to gain access to this trial. First, you could have not had a pCR to neoadjuvant chemotherapy or for ER-positive disease have at least four positive lymph nodes or for triple-negative disease, have a positive lymph node or at least a T2 tumor...
From OlympiAD and EMBRACA of the benefit of PARP inhibitors for metastatic breast cancer that has BRCA alterations. In this study OlympiA, looked at this in the adjuvant setting. So, it was high risk patients that were HER2-negative. And there were a few categories you could fall into to gain access to this trial. First, you could have not had a pCR to neoadjuvant chemotherapy or for ER-positive disease have at least four positive lymph nodes or for triple-negative disease, have a positive lymph node or at least a T2 tumor.
So, we could say that this is a little bit of our higher risk patients that were HER2-negative. They all had surgery. They all had chemotherapy with anthrocyclin and a taxane, et cetera. And then they either went on to supportive care or watchful waiting, which is the standard in the adjuvant setting or they received olaparib for one year. We saw an 8.8% improvement in invasive disease-free survival. So, not seeing any cancer come back and a 7.1% improval and distant disease-free survival.
So, this was pretty exciting. There certainly was some toxicity with agents. Most of it, the grade three, grade four toxicity was actually hematologic toxicity. So, decrease in white blood cell counts, neutrophils, anemia, et cetera. So, in the grand scheme of things, those side effects tend to be a little bit easier to tolerate for patients, it’s a laboratory side effect. Certainly, PARP inhibitors do also have some fatigue that can be a challenge for patients. So, we also saw a little bit of a trend towards improved overall survival although that’s not statistically significant yet, but the hazard ratio is 0.68.
I think this has several implications. I think that this drug will be approved in the adjuvant setting for these high-risk patients. I also think what it’s going to lead to is increased access and coverage for BRCA testing for patients. It really wasn’t until our approval of olaparib and talazoparib in the metastatic setting that we had a blanket approval for all HER2-negative patients to have BRCA testing. And now that we have a therapeutic in the early space, I think this full family history and tree, et cetera, having to sometimes fight with insurance companies for coverage, hopefully, we’ll go away and we’re going to have more universal BRCA testing.
I’m hopeful that actually identifying these patients and the families that harbor this alteration may even go on to prevent cancers as we have a better idea of who needs risk mitigation strategies in this space.
Dr. Hamilton discloses research funding (payable to institution only, no personal funds) from : OncoMed, Genentech/Roche, Zymeworks, Rgenix, ArQule, Clovis, Silverback Therapeutics, Millenium, Acerta Pharma, Sermonix Pharmaceuticals, Torque, Black Diamond, Karyopharm, Infinity Pharmaceuticals, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Fochon, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Hospital, Hutchinson MediPharma, MedImmune, SeaGen, Puma Biotechnology, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Takeda, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, Abbvie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, Merck, PharmaMar, Olema, Polyphor, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs
Dr. Hamilton discloses consulting/advisory role payments( to institution only, no personal funds accepted) from: Genentech/Roche, Boehringer Ingelheim, Novartis, Dantari, Lilly, Merck, Puma Biotechnology, Silverback Therapeutics, CytomX, Pfizer, Mersana, Black Diamond, H3 Biomedicine, Daiichi Sankyo, AstraZeneca, Arvinas, Deciphera Pharmaceuticals, Eisai, Seagen