Background

The OlympiAD study (NCT02000622) showed a significant progression-free survival benefit for olaparib monotherapy over chemotherapy treatment of physician's choice (TPC) in patients (pts) with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm). We examined olaparib tolerability in these pts to further characterize the most common adverse events (AEs).

Methods

OlympiAD was a randomized, open-label, Phase III study in gBRCAm, HER2-negative mBC pts who had received ≤2 chemotherapy lines in the metastatic setting. Pts were randomized 2:1 to olaparib tablet (300 mg bid) or single-agent TPC (capecitabine, eribulin or vinorelbine). Treatment continued until disease progression or unacceptable toxicity.

Results

302 pts were randomized to olaparib (n=205) or TPC (n=97). Six TPC pts declined study treatment due to treatment allocation and were excluded from safety analyses. There were fewer Grade ≥3 AEs with olaparib vs TPC (36.6% vs 50.5%, respectively) and a low rate of discontinuation due to toxicity (4.9% for olaparib vs 7.7% for TPC). Anemia, nausea, vomiting, fatigue and headache were more frequent with olaparib, and neutropenia, decreased white blood cells (WBC) and palmar-plantar erythrodysesthesia (PPE) were more common with TPC. Incidence and outcome for the most common AEs (>20% pts in either arm) are shown in the table. There were no Grade ≥3 nausea or vomiting with olaparib. The first onset of nausea in either arm was typically within the first month of treatment. Prevalence of nausea with olaparib treatment was highest in the first 3 months (˜30% of pts), decreasing to ˜15% for the remainder of the study period. Grade ≥3 anemia was more frequent in the olaparib versus TPC arms. More olaparib pts required blood transfusion (18.0%) than TPC pts (5.5%), and there was more concomitant use of erythropoietin stimulating agents with olaparib than TPC (5.9% vs 1.0%, respectively). Anemia onset was early, typically in the first 3 months of starting treatment. The prevalence of anemia was relatively stable over time. Grade ≥3 neutropenia was more frequent in pts receiving TPC instead of olaparib. There was a slightly higher incidence of concomitant granulocyte-colony stimulating factor treatment with TPC (8.2%) vs olaparib (5.4%).

  Olaparib N=205 (%) TPC N=91 (%) 
  Any grade [≥G3] Dose reduction [interruption] Discontinuation Any grade [≥G3] Dose reduction [interruption] Discontinuation 
Nausea 58 [0] 1 [2] 35 [1] 2 [0] 
Vomiting 30 [0] 1 [2] 15 [1] 2 [0] 
Diarrhea 21 [1] 0 [1] 22 [0] 3 [1] 
Anemia 40 [16] 14 [15] 26 [4] 1 [2] 
Neutropenia 27 [9] 7 [10] 50 [26] 14 [18] 
Decreased WBC 16 [3] 1 [4] 21 [10] 4 [1] 
Fatigue 29 [3] 2 [2] 23 [1] 1 [1] 
Headache 20 [1] 0 [0] 15 [2] 1 [0] 
PPE 1 [0] 0 [0] 21 [2] 8 [6] 
  Olaparib N=205 (%) TPC N=91 (%) 
  Any grade [≥G3] Dose reduction [interruption] Discontinuation Any grade [≥G3] Dose reduction [interruption] Discontinuation 
Nausea 58 [0] 1 [2] 35 [1] 2 [0] 
Vomiting 30 [0] 1 [2] 15 [1] 2 [0] 
Diarrhea 21 [1] 0 [1] 22 [0] 3 [1] 
Anemia 40 [16] 14 [15] 26 [4] 1 [2] 
Neutropenia 27 [9] 7 [10] 50 [26] 14 [18] 
Decreased WBC 16 [3] 1 [4] 21 [10] 4 [1] 
Fatigue 29 [3] 2 [2] 23 [1] 1 [1] 
Headache 20 [1] 0 [0] 15 [2] 1 [0] 
PPE 1 [0] 0 [0] 21 [2] 8 [6] 

AEs of any cause. MedDRA preferred terms are combined for 1) anemia and 2) neutropenia

Conclusions

Gastrointestinal toxicity in either arm was mostly mild to moderate, and typically reported early after treatment initiation. Anemia was more frequent in olaparib pts but rarely led to treatment cessation. Olaparib tablets were generally well tolerated in HER2-negative mBC pts with a gBRCAm, with a lower rate of Grade ≥3 AEs compared with chemotherapy.

Citation Format: Domchek SM, Robson M, Im S-A, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Conte P, Bannister W, Goessl C, Runswick S, Goel S, Tung N. Tolerability of olaparib monotherapy versus chemotherapy in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation: OlympiAD [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-12.