Comparison of pembrolizumab/chemotherapy versus olaparib from a practical standpoint

Comparative aspectOlaparibPembrolizumab/Chemotherapy
Clinical trialOlympiADKeynote 355
Eligibility in mTNBCgBRCA, sBRCA, gPALB2*CPS ≥ 10
Response rate reported60%41%
Median duration of response6.4 Months (IQR, 2.8 to 9.7) in the olaparib group compared to 7.1 months (IQR, 3.2 to 12.2) in the standard chemotherapy group12.8 Months (95% CI 9.9–25.9) in pembrolizumab/chemotherapy group compared to 7.3 months (95% CI 5.5–15.4) in the chemotherapy group
Median time to onset of response47 DaysNot reported
Median PFS7.0 Months versus 4.2 months in the olaparib group compared to the standard-therapy group respectively (HR 0.58; 95% Cl 0.43–0.80; P < 0.001).9.7 Months with pembrolizumab-chemotherapy compared to 5.6 months with placebo-chemotherapy respectively; HR 0.65, 95% CI 0.49–0.86; one-sided P = 0.0012 (co-primary objective met)
OSNo OS benefit in the ITT. OS of 22.6 months compared to 14.7 months if used in the 1st line setting (HR 0.55; 95% CI 0.33–0.95, P = 0.02)**OS of 23.0 months compared to 16.1 months in the placebo-chemotherapy group (HR 0.73; 95% CI 0.55–0.95; P = 0.0093)



Active severe autoimmune disease
Possible adverse effectsMyelosuppression, nausea, vomiting, risk of MDS/AML, pneumonitisAny autoimmune adverse events including but not limited to irreversible hypophysitis, adrenal insufficiency, thyroiditis, fatal cardiomyositis
ConvenienceOral therapy requiring monthly follow up to monitorIV therapy every 3 weeks

* Patients with HER2 negative MBC with gPALB2 or sBRCA1/2 mutations were found to benefit from treatment with olaparib according to TBCRC 048, a phase II trial of olaparib for MBC and homologous recombination-related gene mutations; ** post hoc analysis. IQR: interquartile range; MDS: myelodysplastic syndrome; AML: acute myeloid leukemia; IV: intravenous