NICE Guidance Supports Olaparib Use in BRCA-Mutant Breast, Prostate Cancer

The National Institute for Health and Care Excellence (NICE) announced final draft guidance recommending the PARP inhibitor olaparib (Lynparza) for patients withHER2-negative, high-risk early breast cancer harboring a BRCA1/2 mutation, as well as for those with previously treated hormone-relapsed metastatic prostate cancer with a BRCA1/2 mutation. NICE anticipates publishing the final guidance in May 2023.¹

“We know how important it is for [individuals] with these types of cancer to have more treatment options that enable them to maintain or improve their quality of life,” Helen Knight, director of medicines evaluation at NICE said in a news release.¹ “For adults with this type of early breast cancer, being able to have a targeted treatment after surgery and chemotherapy will increase the chance of curing the disease and reduce the likelihood of developing incurable advanced disease. For adults with advanced prostate cancer, it can also mean delaying chemotherapy and its associated [adverse] effects and allowing them to have more time with their families and loved ones.”

The decision reversed an earlier draft decision from NICE that did not recommend olaparib for adult patients with breast cancer who have already had treatment with chemotherapy prior to or following surgery. NICE has made positive recommendations in its prior appraisals of breast cancer treatments since 2016 (n = 19).¹

The recommendations in both prostate and breast cancer considered cost-effectiveness estimates in addition to clinical trial evidence. Findings from both estimates showed that the cost-effectiveness was within what NICE considered an acceptable use of National Health Service (NHS) resources.^2,3

Regarding the breast cancer recommendation, NICE endorsed olaparib as a monotherapy or in combination with endocrine therapy. The agent was recommended for patients who have received treatment with neoadjuvant or adjuvant chemotherapy.²

NICE considered evidence from AstraZeneca, the manufacturer of olaparib, in making their recommendation, namely, clinical trial evidence from the phase 3 OlympiA trial (NCT02032823). The randomized trial compared olaparib with placebo in patients with BRCA-mutant, HER2-negative, high-risk early breast cancer following chemotherapy, surgery, and radiation therapy.²

The primary end point was invasive disease-free survival (iDFS). Distant disease-free survival (DDFS) and overall survival (OS) represented secondary end points.²

Findings from the study showed that, at a median follow-up of 3.5 years (IQR, 2.5-4.5) in the intention-to-treat population, patients in the olaparib arm (n = 921) experienced a significant OS benefit compared with those in the placebo arm (n = 915; HR, 0.68; 98.5% CI, 0.47-0.97; P = .0009). Additionally, 4-year OS, iDFS, and DDFS rates all favored the olaparib arm: 89.8% vs 86.4%; 82.7% vs 75.4%; and 86.5% vs 79.1%.⁴

In their prostate cancer recommendation, NICE advocated for olaparib for patients whose disease had progressed following treatment with hormonal agents, such as enzalutamide (Xtandi) and abiraterone acetate (Zytiga).³

NICE cited clinical trial evidence from the phase 3 PROfound study (NCT02987543), which compared olaparib with enzalutamide or abiraterone acetateamong patients with metastatic castration-resistant prostate cancer. The primary end point was radiographic progression-free survival and secondary end points included OS.³

Findings from the trial showed that patients in the licensed population and the BRCA-mutation prior taxane subgroup treated with olaparib experienced a higher median progression-free survival (PFS) compared with those who received abiraterone acetate or enzalutamide, 9.0 months (95% CI, 7.4-10.8) vs 1.9 months (95% CI, 1.7-3.5), respectively. The median OS in this patient population also favored the olaparib arm, 17.5 months (95% CI, 13.0-25.3) vs 11.9 months (95% CI, 8.2-15.2), respectively.³

However, NICE noted in their draft guidance that the comparator treatments in PROfound did not reflect NHS practice. Thus, they used findings from the phase 3 CARD trial (NCT02485691) to make an indirect comparison of olaparib with cabazitaxel. Findings showed that treatment with olaparib provided an OS and a PFS benefit compared with cabazitaxel. The precise results were not reported, as AstraZeneca considered them to be confidential.³

“Olaparib represents an important development in the treatment of early breast and advanced prostate cancer and today’s announcement addresses a significant need by giving people with these types of cancer access to an effective, targeted treatment,” Knight added in the news release.¹

References

1. NICE final draft guidance recommends olaparib for early breast cancer and metastatic prostate cancer following new commercial deals. News release. National Institute for Health and Care Excellence. April 6, 2023. Accessed April 7, 2023. https://www.nice.org.uk/
2. Olaparib for adjuvant treatment of BRCA mutation-positive HER2-negative high-risk early breast cancer after chemotherapy. National Institute for Health and Care Excellence. April 2023. Accessed April 7, 2023. https://www.nice.org.uk/
3. Geyer CE Jr, Garber JE, Gelber RD, et al; OlympiA Clinical Trial Steering Committee and Investigators. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022;33(12):1250-1268. doi:10.1016/j.annonc.2022.09.159
4. Olaparib for previously treated BRCA mutation-positive hormone-relapsed metastatic prostate cancer. National Institute for Health and Care Excellence. April 2023. Accessed April 7, 2023. https://www.nice.org.uk/