Relevance of Platinum-free Interval and <i>BRCA</i> Reversion Mutations for Veliparib Monotherapy after Progression on Carboplatin/Paclitaxel for g<i>BRCA</i> Advanced Breast Cancer (BROCADE3 Crossover)

Puhalla, Shannon; Dièras, Véronique; Arun, Banu K.; Kaufman, Bella; Wildiers, Hans; Han, Hyo S.; Ayoub, Jean-Pierre; Stearns, Vered; Yuan, Yuan; Helsten, Teresa; Riley-Gillis, Bridget; Murphy, Erin S.; Kundu, Madan G.; Wu, Meijing; Maag, David; Ratajczak, Christine K.; Ramathal, Cyril; Friedlander, Michael

doi:10.1158/1078-0432.ccr-21-0748

Cited by 10 publications

(8 citation statements)

References 36 publications

(51 reference statements)

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“…The gBRCA testing in TNBC/HER2-negative BC patients is potentially cost-effective The cost-effectiveness of the first-line use of PARPi or the universal testing in the general population of BC is not convincing [36][37][38][39][40][41][42]. Tuffaha et al reported the cost-effectiveness of the gBRCA testing established at the 10% pretest probability threshold [43]; hence expanding the gBRCA test from TNBC to all HER2-negative BC patients is potentially cost-effective, considering the high prevalence (~9.7%) of gBRCA mutations in HER2-negative BC patients.…”

Section: Primary Findingsmentioning

confidence: 99%

All HER2-negative breast cancer patients need gBRCA testing: cost-effectiveness and clinical benefits

Luo

et al. 2022

Br J Cancer

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Background The OlympiA trial demonstrated the benefits of adjuvant usage of olaparib for high-risk patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) and germline BRCA (gBRCA) mutation. This provoked thoughts on the clinical criteria of gBRCA testing. This study aims to estimate the costs and benefits of gBRCA testing and adjuvant olaparib therapy for patients with triple-negative breast cancer (TNBC) and hormone-receptor (HR)-positive and HER2-negative BC in China and the United States of America (USA). Methods We used a Markov chain decision tree analytic model to compare three gBRCA screening policies in China and the USA: (1) no gBRCA testing; (2) selected gBRCA testing and (3) universal gBRCA testing for nonmetastatic TNBC and HR-positive HER2-negative BC patients. We modelled the benefit of systemic therapy and risk-reducing surgeries among patients identified with pathogenic or likely pathogenic variants (PVs) in BRCA1 and BRCA2. Results Changing from the selected gBRCA testing to the universal gBRCA testing in TNBC patients is cost-effective, with the incremental cost-effectiveness ratios (ICERs) being 10991.1 and 56518.2 USD/QALY in China and the USA, respectively. Expanding universal gBRCA testing to HR-positive HER2-negative BC and TNBC patients has ICERs of 2023.3 and 16611.1 USD/QALY in China and the USA, respectively. Discussion By performing gBRCA testing on all HER2-negative BC patients, adjuvant olaparib can be offered to high-risk patients with a PV in BRCA1 or BRCA2. These patients are also candidates for risk-reducing surgeries, an important aspect of their survivorship care, and these interventions can improve survival outcomes. With the willingness-to-pay thresholds being 31,500.0 and 100,000.0 USD per QALY gained in China and the USA, respectively, universal gBRCA testing is likely cost-effective for all HER2-negative BC patients. This simplified criterion of gBRCA testing for BC is recommended for adoption by current guidelines in China and the USA.

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Section: Primary Findingsmentioning

confidence: 99%

All HER2-negative breast cancer patients need gBRCA testing: cost-effectiveness and clinical benefits

Luo

et al. 2022

Br J Cancer

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“…Studies have confirmed that low concentrations of taxane‐based drugs can upregulate the expression of BRCA1 in normal breast cells and breast cancer cells with low BRCA1 expression 6,7 . In a portion of clinical cases of taxane resistance, various pathways of acquired taxane resistance were activated, in which BRCA1 expression was found to be up‐regulated 8 . Regarding the mechanism of BRCA1 mutation leading to drug resistance of paclitaxel, we believe that it is related to homologous recombination (HR) pathway, which is a DNA repair mechanism in which BRCA proteins play a major role.…”

Section: Discussionmentioning

confidence: 93%

Case report: Emerging BRCA mutation confers benefit from olaparib after chemotherapy intolerance in advanced triple‐negative breast cancer

Shen,

Wu,

et al. 2024

Clinical Case Reports

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Key Clinical MessageIn a patient with metastatic breast cancer, an acquired BRCA mutation in the BRCA gene was detected, resulting in benefits from olaparib treatment. This underscores the importance of ongoing genetic phenotype testing after paclitaxel chemotherapy.AbstractTriple‐negative breast cancer (TNBC) is associated with a poor prognosis and elevated mortality risk. BRCA mutations are commonly regarded as prevalent mutations in TNBC patients, strongly associated with congenital familial heredity. Dynamic changes in mutation sites, however, are rarely reported. In this case report, we report a 59‐year‐old TNBC patient who developed pulmonary metastases post‐chemoradiotherapy. No BRCA mutations were detected through NGS. After 7.6 months of nab‐paclitaxel treatment, the patient experienced progression of lung metastases, and BRCA mutations were detected through NGS testing. Subsequent administration of olaparib resulted in a reduction in lung metastasis, demonstrating significant therapeutic efficacy. This case underscores the infrequent occurrence of treatment‐induced BRCA mutations and emphasizes the significance of dynamic NGS genetic testing for real‐time assessment of a patient's mutational status.

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“…Among them, a platinum-free interval longer than 180 days was correlated with greater veliparib activity. 49 Regarding combination with immunotherapy, the TOPA-CIO phase II trial explored the safety and efficacy of niraparib in combination with pembrolizumab in patients with metastatic triple negative breast cancer (TNBC) including a cohort of patients with tumor BRCA1/2 mutation. 50 Among 15 patients with a tumor BRCA1/2 mutation, the objective response rate (ORR) was 47% and the median PFS was 8.3 months (95% CI, 2.1-not estimable).…”

Section: Practical Applicationsmentioning

confidence: 99%

Current Systemic Treatments for the Hereditary Cancer Syndromes: Drug Development in Light of Genomic Defects

Hasanov

Pimentel

Cruellas

et al. 2022

American Society of Clinical Oncology Educational Book

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Advances in the genetic basis of different tumors have led to identification of tumor vulnerabilities that can be turn into targeted therapies. In this regard, PARP inhibitors cause synthetic lethality with tumors harboring BRCA1 or BRCA2 genetic alterations. On the other hand, tumors with microsatellite instability, either due to germline or sporadic alterations, are candidates for immune checkpoint inhibitors. Finally, patients with von Hippel-Lindau disease who carry a germline alteration in the VHL gene may benefit form belzutifan, a hypoxia-inducible factor 2 alpha inhibitor. Overall, research on the underlying pathological mechanisms of these tumors has provided new therapeutic opportunities that might be expanded to other sporadic tumors with similar biology.

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Relevance of Platinum-free Interval and BRCA Reversion Mutations for Veliparib Monotherapy after Progression on Carboplatin/Paclitaxel for gBRCA Advanced Breast Cancer (BROCADE3 Crossover)

Cited by 10 publications

References 36 publications

All HER2-negative breast cancer patients need gBRCA testing: cost-effectiveness and clinical benefits

All HER2-negative breast cancer patients need gBRCA testing: cost-effectiveness and clinical benefits

Case report: Emerging BRCA mutation confers benefit from olaparib after chemotherapy intolerance in advanced triple‐negative breast cancer

Current Systemic Treatments for the Hereditary Cancer Syndromes: Drug Development in Light of Genomic Defects

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