Adjuvant treatment with the PARP inhibitor olaparib showed beneficial effects for patients with BRCA1/2 mutations and high-risk, HER2-negative, early-stage, primary breast cancer. In addition, patient-reported outcomes demonstrate no negative impact on the quality of life.
OlympiA (NCT02032823) is a randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of the PARP inhibitor olaparib in patients with germline BRCA1/2 mutations and high-risk, HER2-negative, early-stage, primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. A recently published interim analysis at a median follow-up of 2.5 years showed the 3-year invasive disease-free survival (IDFS) to be 85.9% in the olaparib group and 77.1% in the placebo group (difference of 8.8%; HR for invasive disease or death 0.58; P<0.001) . However, chemotherapy has substantial acute toxicity in early-stage breast cancer, which delays recovery. Additional adjuvant therapy could add acute toxicity, leading to a longer delay in recovery. Therefore, in OlympiA, patient-reported outcomes (PROs) were collected to guide discussion between physicians and patients regarding the risks and benefits of additional adjuvant therapy. Dr. Patricia Ganz (UCLA School of Medicine, CA, USA) presented the results . The OlympiA trial included 1,836 patients with HER2-negative, germline BRCA1/2-mutated, early-stage breast cancer who had received local treatment and neoadjuvant or adjuvant chemotherapy. Participants were randomized (1:1) to 1 year adjuvant olaparib or placebo. PRO assessments were done at baseline and every 6 months, up to 2 years. The primary hypothesis stated that patients on olaparib may experience greater fatigue severity at 6 and 12 months compared with patients on placebo. Secondary hypotheses focussed on gastrointestinal symptom severity and quality of life. Data from 1,535 patients were available for these analyses. Baseline scores for fatigue were well balanced between study arms and clinically meaningful lower in OlympiA patients compared with healthy women. Patients treated with olaparib experienced a higher increase in fatigue scores at 6 and 12 months compared with patients treated with placebo. However, the difference between groups (-1.3 at 6 months and -1.5 at 12 months) did not reach the prespecified border of a clinically meaningful difference of 3 points. At 18 and 24 months, there were no differences in fatigue scores between patients treated with olaparib or placebo. Scores for nausea and vomiting were clinically meaningfully higher in patients treated with olaparib at 6 and 12 months, not at 18 and 24 months. Diarrhea was not increased for either treatment group during the study. Physical functioning, emotional functioning, nor global health status was impaired over time for either treatment group. “In conclusion, these results show that treatment with olaparib comes with a clinically meaningful increase in nausea and vomiting during the first year of treatment,” said Dr. Ganz. “Olaparib does not induce a clinically meaningful increase of fatigue, diarrhea, or quality of life.”
- Tutt ANJ, et al. N Engl J Med 2021;384:2394-2405.
- Ganz PA, et al. Quality of life results from OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high risk HER2 negative breast cancer. SABCS 2021 Virtual Meeting, abstract GS4-09.
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