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Olaparib Plus Durvalumab Show Durable Activity in Germline BRCA+ Breast, Ovarian Cancer

Wayne Kuznar
Published Online:3:30 PM, Wed October 9, 2019

The median follow-up for OS was 19.8 months, at which time the median OS was 21.5 months in the full analysis set, 20.5 months in the TNBC cohort, 22.4 months in the HR-positive subgroup, 23.4 months in those receiving 0 or 1 prior lines of chemotherapy, and 16.9 months in those receiving 2 prior lines.

PD-L1 expression was ≥1% in tumor cells in 33% of patients and ≥1% in immune cells in 57% of patients using the Ventana PD-L1 (SP263) assay. When OS was examined by PD-L1 status in tumor cells, the median OS was 23.9 months in patients with PD-L1 tumor cell expression ≥1% compared with 18.8 months in those with PD-L1 expression in tumor cells <1%. In patients with PD-L1 expression ≥1% in immune cells, the median OS was 21.5 months, compared with 16.9 months in those with immune cell PD-L1 expression <1%.

Patients with expression of CD3-positive tumor infiltrating lymphocytes (TILs) ≥458 cell/mm2 had a median OS of 21.5 months, compared with 19.2 months in those with CD3 TILs <458 cell/mm2. The presence of CD8-positive TILs also appeared to affect survival: those with CD8 TIL expression ≥140 cell/mm2 had a median OS of 23.4 months versus 18.6 months in those with CD8 TIL expression <140 cell/mm2.

A subset of 9 patients had disease progression at or before 28 weeks. Of these, potential mechanisms of resistance were BRCA2 reversion mutation (n = 1), lack of BRCA2 allele-specific loss of heterozygosity (n = 1), TP53BP1 mutation (n = 1), and PD-L1 and PD-L2 amplification (n = 1).

Safety analysis included all 34 patients. “There were no new safety signals,” said Domchek. “Longer follow-up indicates that the olaparib/durvalumab combination continues to be well tolerated.”

Dose reduction of olaparib was required because of AEs in 6 (18%) patients and the dose of durvalumab had to be reduced in 7 (21%) patients because of AEs. One patient discontinued olaparib and 3 discontinued durvalumab because of AEs. Twelve (35%) patients had an immune-mediated AE, with hypothyroidism (15%) being the most common.

“Further research is needed to determine if there are particular subsets of patients who benefit from the addition of durvalumab to olaparib,” said Domchek.
 
References
  1. Drew Y, Kaufman B, Banerjee S, et al. Phase II study of olaparib + durvalumab (MEDIOLA): Updated results in germline BRCA-mutated platinum-sensitive relapsed (PSR) ovarian cancer (OC). Presented at 2019 ESMO Congress; September 27-October 1, 2019; Barcelona, Spain. Abstract 1190PD.
  2. Domchek SM, Postel-Vinay S, Im S-A, et al. Phase II study of olaparib (O) and durvalumab (D) (MEDIOLA): Updated results in patients (pts) with germline BRCA-mutated (gBRCAm) metastatic breast cancer (MBC). Presented at 2019 ESMO Congress; September 27-October 1, 2019; Barcelona, Spain. Abstract 1191O.


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