KEY TAKEAWAYS
- A phase 3 OlympiA trial tested olaparib in patients with certain genetic mutations (BRCA1/2) to improve outcomes for early breast cancer (EBC).
- The trial’s second prespecified IA demonstrated a significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC.
- Improvements in the previously reported, statistically significant endpoints of iIDFS and DDFS with no new safety signals.
- Median follow-up of 3.5 years, the olaparib group had a 4-year OS of 89.8%, while the placebo group had a 4-year OS of 86.4%, translating to a 3.4% improvement in OS for the olaparib group.
- Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups, and no new safety signals were identified, including no new cases of acute myeloid leukemia or myelodysplastic syndrome.
Patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer were evaluated in the randomized, double-blind OlympiA trial, which compared 1 year of oral poly (adenosine diphosphate-ribose) polymerase inhibitor olaparib to matching placebo as adjuvant therapy (EBC). Invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) have both shown statistically significant improvement since the first prespecified interim analysis (IA).
Overall mortality was lower in the olaparib group compared to the placebo group, although the difference was not statistically significant (OS). Updates to IDFS, DDFS, and safety have been included in this, the second IA of OS, which has been reported. Following (neo)adjuvant chemotherapy, surgery, and radiation therapy (if needed), 1,836 patients were randomly assigned to receive either olaparib or a placebo. In addition to the study of medicine, endocrine therapy was used for hormone receptor-positive tumors. For OS at this IA to be statistically significant, P0.015 was needed.
The second IA of OS showed a significant improvement in the olaparib group compared to the placebo group with a median follow-up of 3.5 years [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. The olaparib group had a four-year OS of 89.8%, while the placebo group had an OS of 86.4% (Δ3.4%, 95% CI -0.1% to 6.8%). IDFS after 4 years was 82.7% in the olaparib group compared to 75.4% in the placebo group (Δ 7.3%, 95% CI 3.0% to 11.5%), while DDFS at 4 years was 86.5% compared to 79.1% (Δ 7.4%, 95% CI 3.6% to 11.5%).
It was found in the analysis of subsets that all major groups benefited from treatment for OS, IDFS, and DDFS. There were no newly reported occurrences of adverse events, such as leukemia or myelodysplastic syndrome, and no new safety flags were found. After a median follow-up of 3.5 years, patients with gBRCA1/2pv-associated EBC who received adjuvant olaparib had significantly longer overall survival than those who received placebo. There were no new safety flags.
Source: https://pubmed.ncbi.nlm.nih.gov/36228963/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02032823
C E Geyer Jr, J E Garber, R D Gelber, G Yothers, M Taboada, L Ross, P Rastogi, K Cui, A Arahmani, G Aktan, A C Armstrong, M Arnedos, J Balmaña, J Bergh, J Bliss, S Delaloge, S M Domchek, A Eisen, F Elsafy, L E Fein, A Fielding, J M Ford, S Friedman, K A Gelmon, L Gianni, M Gnant, S J Hollingsworth, S-A Im, A Jager, Ó Þ Jóhannsson, S R Lakhani, W Janni, B Linderholm, T-W Liu, N Loman, L Korde, S Loibl, P C Lucas, F Marmé, E Martinez de Dueñas, R McConnell, K-A Phillips, M Piccart, G Rossi, R Schmutzler, E Senkus, Z Shao, P Sharma, C F Singer, T Španić, E Stickeler, M Toi, T A Traina, G Viale, G Zoppoli, Y H Park, R Yerushalmi, H Yang, D Pang, K H Jung, A Mailliez, Z Fan, I Tennevet, J Zhang, T Nagy, G S Sonke, Q Sun, M Parton, M A Colleoni, M Schmidt, A M Brufsky, W Razaq, B Kaufman, D Cameron, C Campbell, (2022). 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. Annals of Oncology, 33(12), pp.1250–1268. doi:https://doi.org/10.1016/j.annonc.2022.09.159.
