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Efficacy

Both olaparib and talazoparib have approvals for use in gBRCA-mutated breast cancer (HER-2 negative) [1-5].

Olaparib was the first PARP inhibitor to demonstrate benefit over standard treatment (investigator’s choice of one out of three standard non-platinum chemotherapy regimens) in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer [1].

In the phase III, randomized, open-label OlympiAD trial, median progression-free survival for olaparib (300 mg twice daily) was 7.0 months compared to 4.2 months for standard of care (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.43 – 0.80; p<0.0009). Time to second progression or death (TTSP) was longer for olaparib versus chemotherapy, but overall survival was similar for both study arms. More patients in the standard chemotherapy group received further treatment with PARP inhibitors, platinum-based therapy, or other cytotoxic chemotherapy after first progression than in the olaparib group. The percentage of patients receiving first line treatment was 29% in each group. Olaparib was associated with fewer grade ≥3 adverse events than the standard-therapies (36.6% versus 50.5%). Health-related quality of life (HRQOL) measures improved slightly for olaparib and deteriorated slightly for standard therapy group, and overall olaparib treatment resulted in a delay in any clinically meaningful decrease in the QLQC30 score [1].

Talazoparib has also demonstrated benefit in patients with gBRCA mutations, HER2-negative, locally advanced or metastatic breast cancer [2]. In the phase III, randomised, open-label EMBRACA trial, the talazoparib patients had a median progression-free survival of 8.6 months versus 5.6 months with physician’s choice of non-platinum chemotherapy (HR 0.54; 95% CI 0.41 – 0.71; p<0.001). Overall survival was similar for both treatment groups; further anticancer treatment was received by 62% of patients in the talazoparib group, and 68% in the standard chemotherapy group. 39% of the patients in each arm of the study were receiving first-line treatment. Grade 3-4 haematologic adverse events occurred more often with talazoparib (55% vs 38%), whereas nonhaematological grade 3 events were similar for both treatment arms (32% and 38%). Talazoparib treatment was associated with a significant overall improvement in HRQOL from baseline whereas chemotherapy saw significant deterioration, and talazoparib significantly delayed time to deterioration compared with chemotherapy [6].

Table 2: Key efficacy data from trials of PARP inhibitors in breast cancer

Olaparib (tablets) vs chemotherapy (OlympiAD): gBRCA-mutated, HER2-negative metastatic BC [1].

PFS

7.0 vs 4.2; HR 0.58 (95% CI 0.43-0.80); p<0.001

TTSP

13.2 vs 9.3; HR 0.57 (95% CI 0.40-0.83); p=0.003

OS

19.3 vs 19.6; HR 0.90 (95%CI 0.63-1.29); p=0.57

ORR

59.9% vs 28.8%

Talazoparib vs chemotherapy (EMBRACA): gBRCA-mutated, HER2-negative locally advanced or metastatic BC [2].

PFS

8.6 (7.2-9.3) vs 5.6 (4.2-6.7); HR 0.54 (95%CI 0.41-0.71) p<0.001

OS

22.3 (18.1-26.2) vs 19.5 (16.3-22.4); HR 0.76 (95%CI 0.55-1.06) p=0.11

ORR*

62.6% vs 27.2%; OR 5.0 (95%CI 2.9-8.8) p<0.001

Unless otherwise indicated all data is in months (95% CI).
*Investigator assessed.
Blinded independent central review.
CI, confidence interval; gBRCA: germline BRCA mutations, HR, hazard ratio, OR, Odds Ratio, ORR: Overall Response Rate, OS: Overall Survival, PFS: Progression Free Survival, TTSP: Time to Second Progression.

References

  1. Robson M, Im SA, Senkus E et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017; 377: 523-533.
  2. Litton JK, Rugo HS, Ettl J et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med 2018; 379: 753-763.
  3. European Medicines Agency. Olaparib Summary of Product Characteristics. 2019.
  4. Food and Drug Administration. Olaparib. 2014.
  5. Food and Drug Administration. FDA approves talazoparib for gBRCAm HER2-negative locally advanced or metastatic breast cancer. 2018
  6. Ettl J, Martin M, Roché H et al. Quality of life with talazoparib versus physician’s choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Annals of Oncology 2018; 29: 1939-1947.

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