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Response to Immune Checkpoint Inhibitors Not Tied to BRCA 1/2 Mutations in Ovarian Cancer
Chicago, Illinois—Results from a recent study being presented at the 2019 ASCO Annual Meeting show that in heavily pretreated patients with ovarian cancer being given immune checkpoint inhibitors, BRCA 1/2 mutations were not related to improved response or survival.
“Alterations in the DNA mismatch repair pathway increase susceptibility to immune checkpoint inhibition (ICI). Tumors with BRCA-related DNA repair defects may have increased antigenicity, which could drive response to ICI. Responses to ICI in ovarian cancer…have been modest,” according to lead investigator Ying L. Liu, PhD, Memorial Sloan-Kettering Cancer Center - Fellowship (GME Office), New York, and colleagues.
Seeking to determine the relationship between BRCA mutations and response to ICI and survival in recurrent ovarian cancer, Dr Liu et al conducted a retrospective review of 103 women with recurrent ovarian cancer and BRCA mutations (90 germline and 33 somatic testing) who received ICI between January 2013 and July 2018 at a single center.
They compared clinical characteristics and duration of ICI (long, ≥24 weeks vs short <24 weeks) using BRCA status and calculated progression-free (PFS) and overall survival (OS) from start of ICI via a Kaplan Meier survival analysis. In addition, CoxPH models and a logrank test were used to evaluate survival differences by BRCA status.
“Deleterious germline (g) or somatic (s) BRCA 1/2 mutations were present in 29 (28%) women (12 gBRCA1, 9 gBRCA2, 3 sBRCA1, 5 sBRCA2, 1 gBRCA1/sBRCA1, 3 gBRCA2/sBRCA2, and 1 gBRCA2/sBRCA1),” the investigators said.
Although patients with BRCA mutations had received more previous lines of therapy before ICI (median 5 vs 4; P = .03) and had longer times from diagnosis to ICI than their counterparts without BRCA mutations (median, 54 vs 38.5 months; P = .01), there were no significant differences between the 2 arms in other variables, such as histology (86%, high grade serous), stage at diagnosis (96%, Stage III/IV), and platinum status (83%, resistant; P >.05).
There were 4 (15%) patients with BRCA mutations had longer durations of ICI than 20 (27%) patients without mutations (P = .20). The median PFS was 2.2 months (95% CI, 1.7-2.7) versus 3.4 months (95% CI, 2.1-4.0) respectively (hazard ratio [HR], 1.22; 95% CI, 0.78-1.91; P = .38).
The median OS was 21.3 months (95% CI, 13.7-31.8) versus 19.8 months (95% CI, 13.8-25.3) in those with and without BRCA mutations, respectively, at a median follow-up of 23.3 months. Dr Liu and colleague said that, after adjusting for previous therapy lines and time from diagnosis to ICI, this finding was not significantly different (HR, 1.00; 95% CI, 0.54-1.87; P = .99).
“In our study of heavily pretreated OC pts [ovarian cancer patients] receiving ICI, BRCA 1/2 mutations were not associated with improved response or survival. These findings should be validated in larger studies,” they concluded.—Hina Khaliq
Liu YL, Boland JL, Cadoo KA, et al. Response to immune checkpoint inhibition and survival in BRCA-associated recurrent ovarian cancer. Presented at: the 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 2615.
