Subgroup analysis of olaparib monotherapy versus chemotherapy by hormone receptor and BRCA mutation status in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation: OlympiAD

Senkus-Konefka, E.; Domchek, S; Im, S-A; Xu, Binghe; Armstrong, Anne; Masuda, Norikazu; Delaloge, S; Li, W; Tung, Nadine; Conte, P.F.; Wu, Wei; Goessl, Carsten; Runswick, Sarah; Robson, M. E.

doi:10.1016/s0959-8049(18)30285-5

Cited by 9 publications

(7 citation statements)

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“…41 To evaluate the clinical efficacy of combining the PARP inhibitor niraparib with the PD-1 inhibitor pembrolizumab, the phase II TOPACIO trial (ClinicalTrials.gov identifier: NCT02657889) enrolled 55 patients with advanced or mTNBC and found an ORR of 47% and a median PFS of 8.3 months among the 15 patients with tumor BRCA mutations. 42 Within the limits of cross-trial comparisons, this ORR was slightly lower than the ORRs of 55% and 62% associated with single-agent PARP inhibitor therapy in patients with TNBC and germline BRCA mutations in the OlympiAD (NCT02000622) 43 and EMBRACA 44 (NCT01945775) trials, respectively. However, the median PFS was longer than those observed in the TNBC subgroups of these trials, which were 5.5 and 5.8 months, respectively.…”

Section: Targeted Therapy Combination Regimensmentioning

confidence: 84%

Role of Immunotherapy in Triple-Negative Breast Cancer

Keenan

Tolaney

2020

Journal of the National Comprehensive Cancer Network

363

298

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Immune checkpoint inhibitors (ICIs) have led to durable clinical remissions in many metastatic cancers. However, the single-agent efficacy of ICIs in breast cancer is low, including in triple-negative breast cancer (TNBC), which has several key characteristics that enhance ICI responses. Strategies to improve anticancer immune responses in TNBC are urgently needed to extend survival for patients with metastatic disease. This review presents ICI monotherapy response rates and discusses combination strategies with chemotherapy, targeted therapies, and novel immunotherapies. It concludes with a summary of immunotherapy biomarkers in TNBC and a call to action for future directions of research critical to advancing the efficacy of immunotherapy for patients with TNBC.Although response rates to ICIs are higher in TNBC than in hormone receptor-positive and HER2-positive breast cancers, the single-agent efficacy is still low, with monotherapy response rates ranging from approximately 5% in

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Section: Targeted Therapy Combination Regimensmentioning

confidence: 84%

Role of Immunotherapy in Triple-Negative Breast Cancer

Keenan

Tolaney

2020

Journal of the National Comprehensive Cancer Network

363

298

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“…21 Tumor mutations in BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) (tBRCAmut) cause defects in HRR and are estimated to be present in 20% to 25% of patients with basal-like TNBC. 21,22 In the registrational phase 3 trial of the PARP inhibitor olaparib, 23,24 the subgroup of patients with germline BRCAmut TNBC had an objective response rate (ORR) of 55% and experienced a benefit in PFS compared with patients receiving the physician's choice of treatment (5.6 vs 2.9 months). In the registrational phase 3 trial of talazoparib tosylate, 25,26 patients with germline BRCA mutation TNBC had an ORR of 62% and a PFS of 5.8 months.…”

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confidence: 99%

Open-label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer

et al. 2019

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IMPORTANCE Poly(adenosine diphosphate-ribose) polymerase inhibitor and anti-programmed death receptor-1 inhibitor monotherapy have shown limited clinical activity in patients with advanced triple-negative breast cancer (TNBC).OBJECTIVE To evaluate the clinical activity (primary) and safety (secondary) of combination treatment with niraparib and pembrolizumab in patients with advanced or metastatic TNBC. DESIGN, SETTING, AND PARTICIPANTSThis open-label, single-arm, phase 2 study enrolled 55 eligible patients with advanced or metastatic TNBC irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression at 34 US sites. Data were collected from

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“…Of the 47 efficacy evaluable patients, ORR was 21% overall and 47% in patients with tumor BRCA1/2 mutations [45]. This ORR is comparable to the ORR seen with single-agent PARP inhibitor therapy in patients with metastatic TNBC and germline BRCA1/2 mutations in the OlympiAD and EMBRACA trials, 55% and 62% respectively [38,39]. The addition of immunotherapy may meaningfully prolong PFS in responders, however, with a median PFS of 8.3 months for patients with a BRCA1/2 mutation enrolled in the TOPACIO trial versus 5.5 and 5.8 months for patients enrolled in the OlympiAD and EMBRACA trials, respectively.…”

Section: Parp Inhibitorsmentioning

confidence: 75%

“…In a different model, PARP inhibitors combined with anti-CTLA-4 therapy in BRCA1-deficient ovarian tumor models were found in vitro to induce longterm survival [37]. PARP inhibitors, such as olaparib and talazoparib, as monotherapy are FDA-approved for the treatment of metastatic germline BRCA-mutant breast cancer based on the results from the OlympiAD and EMBRACA trials [38][39][40][41]. BRCA1 mutation carriers develop TNBC more often than BRCA1/2 wild-type counterparts [42] and increasing evidence suggests mutations in other genes involved in the homologous recombination DNA damage repair pathway are associated with TNBC and may predict responsiveness to PARP inhibition [43,44].…”

Section: Parp Inhibitorsmentioning

confidence: 99%

Checkpoint inhibitor therapy for metastatic triple-negative breast cancer

Heeke

Tan

2021

Cancer Metastasis Rev

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Immunotherapy has become a mainstay of cancer treatment in many malignancies, though its application in breast cancer remains limited. Of the breast cancer subtypes, triple-negative breast cancers (TNBCs) are characterized by immune activation and infiltration and more commonly express biomarkers associated with response to immunotherapy. Checkpoint inhibitor therapy has shown promising activity in metastatic TNBC. In 2019, the US FDA granted accelerated approval of atezolizumab, a programmed death-ligand 1 (PD-L1) inhibitor, in combination with nab-paclitaxel for unresectable locally advanced or metastatic PD-L1-positive TNBC, based on the results of the phase III IMpassion130 trial. In 2020, the FDA also granted accelerated approval of pembrolizumab, a PD-1 inhibitor, in combination with chemotherapy for locally recurrent unresectable and metastatic PD-L1-positive TNBC, based on results of the phase III KEYNOTE-355 trial. Additional combination strategies are being explored in the treatment of metastatic TNBC, with the goal of augmenting antitumor activity. In this review, the clinical development of checkpoint inhibitors in the treatment of metastatic TNBC will be discussed, including clinical outcomes with monotherapy and combination therapy regimens, biomarkers that may predict for benefit, and future directions in the field.

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Subgroup analysis of olaparib monotherapy versus chemotherapy by hormone receptor and BRCA mutation status in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation: OlympiAD

Cited by 9 publications

References 0 publications

Role of Immunotherapy in Triple-Negative Breast Cancer

Role of Immunotherapy in Triple-Negative Breast Cancer

Open-label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer

Checkpoint inhibitor therapy for metastatic triple-negative breast cancer

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