NICE Recommends Talazoparib for Advanced BRCA1/2-Mutant, HER2– Breast Cancer

Helen Knight

The National Institute for Health and Care Excellence (NICE) has recommended talazoparib (Talzenna), within its marketing authorization, for the treatment of adult patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA1 or BRCA2 mutations following receipt of an anthracycline, taxane, or both, and endocrine therapy for hormone receptor–positive disease if clinically indicated, according to final draft guidance from the agency.¹

The recommendation reverses the agency’s earlier draft decision to not recommend talazoparib for adults with BRCA1/2-mutant, HER2-negative locally advanced or metastatic breast cancer after prior chemotherapy.²

Prior to the announcement, Pfizer announced an increased discount to the price of the PARP inhibitor.² According to the agency, the cost-effectiveness estimates for the agent, taking into consideration the disease’s severity and effects on quality and length of life, are within the range that is considered an acceptable use of National Health Service (NHS) resources.¹

“[This] announcement addresses a significant need by giving [patients] with these types of cancer access to an additional treatment. And because talazoparib is taken as a once-daily tablet…it’s much more convenient for [patients] who would otherwise need to go into hospital for intravenous chemotherapy,” Helen Knight, director of medicines evaluation at NICE, said in a news release.²

The agent first received approval from the FDA in 2018 for patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.³

Efficacy of the agent was evaluated in the phase 3 EMBRACA trial (NCT01945775), which enrolled 431 patients with germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer. Eligible patients were randomly assigned 2:1 to receive 1 mg of oral talazoparib daily (n = 287) or physician’s choice of chemotherapy (n = 144) consisting of capecitabine, eribulin, gemcitabine, or vinorelbine.⁴

Eligibility criteria required patients to have received no more than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease. Moreover, patients must have received treatment with an anthracycline and/or a taxane, unless contraindicated, in the neoadjuvant, adjuvant, and/or metastatic setting.

The primary end point of the study was progression-free survival (PFS), as assessed by blinded independent central review. Secondary end points were overall survival (OS), safety, and overall response rate.

Previously reported results showed that talazoparib led to a significant improvement in PFS vs chemotherapy (HR, 0.542; 95% CI, 0.413-0.711; P < .0001).

The final OS analysis of the trial was conducted with median follow-up of 44.9 (95% CI, 37.9-47.0) months and 36.8 months (95% CI, 34.3-43.0) for talazoparib and chemotherapy, respectively. At this time, the median OS was 19.3 months (95% CI, 16.6-22.5) with talazoparib vs 19.5 months (95% CI, 17.4-22.4) with chemotherapy, failing to demonstrate a statistically significant benefit with talazoparib (HR, 0.848; 95% CI, 0.670-1.073; P = 0.17). The 12-, 24-, and 36-month PFS rates with talazoparib were 71% (95% CI, 66%-76%), 42% (95% CI, 36%-47%), and 27% (95% CI, 22%-33%), respectively, vs 74% (95% CI, 66%-81%), 38% (95% CI, 30%-47%), and 21% (95% CI, 14%-29%), respectively, with chemotherapy,.

Despite the lack of OS improvement, talazoparib showed significant improvements and delays in time to definitive clinically meaningful deterioration in global health status/quality of life and breast symptoms vs chemotherapy (P < .01).

“Although some uncertainty in the clinical evidence remains, when considering the impact of advanced breast cancer and its effect on quality and length of life, the improved discount from the company means we can now recommend talazoparib for use in the NHS,” Knight concluded.¹

References

1. National Institute for Health and Care Excellence – final draft guidance - talazoparib for treating HER2-negative advanced breast cancer with germline BRCA mutations. NICE. January 2024. Accessed January 22, 2024. https://www.nice.org.uk/guidance/gid-ta10366/documents/674
2. 300 people to benefit from new treatment for advanced breast cancer recommended by NICE following price deal. NICE. January 19, 2024. Accessed January 22, 2024. https://www.nice.org.uk/news/article/300-people-to-benefit-from-new-treatment-for-advanced-breast-cancer-recommended-by-nice-following-price-deal
3. FDA approves talazoparib for gBRCAm HER2-negative locally advanced or metastatic breast cancer. FDA. October 16, 2018. Accessed January 22, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-talazoparib-gbrcam-her2-negative-locally-advanced-or-metastatic-breast-cancer#:~:text=On%20October%2016%2C%202018%2C%20the,advanced%20or%20metastatic%20breast%20cancer
4. Litton JK, Hurvitz SA, Mina LA, et al. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial.Ann Oncol. 2020;31(11):1526-1535. doi:10.1016/j.annonc.2020.08.2098