Messaggi chiave
- OlympiA è uno studio randomizzato di fase III che ha confrontato 1 anno di terapia adiuvante con olaparib rispetto a placebo in pazienti con carcinoma mammario precoce (eBC) ad alto rischio, HER2-, con mutazioni germinali di BRCA1/2. È stata condotta un’analisi degli esiti riferiti dai pazienti, con endpoint primario la fatigue misurata sulla scala FACIT-F.
- L’analisi, comprensiva di un totale di 1538 pazienti, ha evidenziato una differenza statisticamente, ma non clinicamente significativa nella gravità della fatigue a favore del gruppo placebo rispetto a olaparib a 6 e 12 mesi, ma non successivamente. Durante il trattamento, sono emerse alcune differenze clinicamente significative tra i gruppi in relazione ad altri sintomi, come nausea e vomito, non però nelle sottoscale funzionali o nello stato di salute globale.
- I risultati della presente analisi integrano i dati di tossicità registrati dagli sperimentatori e suggeriscono un minimo impatto di olaparib adiuvante sulla fatigue post-chemioterapia e su altre misure di qualità della vita in pazienti con eBC BRCA1/2-mutato, ad alto rischio.
Abstract
Purpose
- The OlympiA randomized phase III trial compared 1 year of olaparib (OL) or placebo (PL) as adjuvant therapy in patients with germline BRCA1/2, high-risk human epidermal growth factor receptor 2-negative early breast cancer after completing (neo)adjuvant chemotherapy ([N]ACT), surgery, and radiotherapy.
- The patient-reported outcome primary hypothesis was that OL-treated patients may experience greater fatigue during treatment.
Methods
- Data were collected before random assignment, and at 6, 12, 18, and 24 months. The primary end point was fatigue, measured with the Functional Assessment of Chronic Illness Therapy-Fatigue scale.
- Secondary end points, assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 item, included nausea and vomiting (NV), diarrhea, and multiple functional domains.
- Scores were compared between treatment groups using mixed model for repeated measures. Two-sided p values <0.05 were statistically significant for the primary end point. All secondary end points were descriptive.
Results
- One thousand five hundred and thirty-eight patients (NACT: 746, ACT: 792) contributed to the analysis. Fatigue severity was statistically significantly greater for OL versus PL, but not clinically meaningfully different by prespecified criteria (≥3 points) at 6 months (diff OL v PL: NACT: -1.3 [95% CI, -2.4 to -0.2]; p = 0.022; ACT: -1.3 [95% CI, -2.3 to -0.2]; p = 0.017) and 12 months (NACT: -1.6 [95% CI, -2.8 to -0.3]; p = 0.017; ACT: -1.3 [95% CI, -2.4 to -0.2]; p = 0.025).
- There were no significant differences in fatigue severity between treatment groups at 18 and 24 months. NV severity was worse in patients treated with OL compared with PL at 6 months (NACT: 6.0 [95% CI, 4.1 to 8.0]; ACT: 5.3 [95% CI, 3.4 to 7.2]) and 12 months (NACT: 6.4 [95% CI, 4.4 to 8.3]; ACT: 4.5 [95% CI, 2.8 to 6.1]).
- During treatment, there were some clinically meaningful differences between groups for other symptoms but not for function subscales or global health status.
Conclusions
- Treatment-emergent symptoms from OL were limited, generally resolving after treatment ended. OL- and PL-treated patients had similar functional scores, slowly improving during the 24 months after (N)ACT and there was no clinically meaningful persistence of fatigue severity in OL-treated patients.