U.S. Oncology Research, The Woodlands, TX
Robert L. Coleman , Amit M. Oza , Domenica Lorusso , Carol Aghajanian , Ana Oaknin , Andrew Dean , Nicoletta Colombo , Johanne I Weberpals , Andrew R. Clamp , Giovanni Scambia , Alexandra Leary , Robert W. Holloway , Margarita Amenedo Gancedo , Peter C.C. Fong , Jeffrey C. Goh , David M. O'Malley , Sandra M. Goble , Lara Maloney , Jonathan A. Ledermann
Background: In ARIEL3 (NCT01968213), rucaparib maintenance treatment led to significant improvement vs placebo for the primary endpoint of investigator-assessed progression-free survival (PFS) in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma responsive to the last line of platinum therapy (Coleman et al. Lancet. 2017;390:1949–61). The largest benefit was observed in pts with carcinomas with a BRCA mutation or high loss of heterozygosity (LOH), a marker of homologous recombination deficiency (HRD). However, rucaparib also improved PFS in pts with carcinomas negative by HRD test (ie, BRCA wild-type with low LOH), a subset of pts for which there is no identified molecular mechanism conferring PARP inhibitor sensitivity. Among these pts (rucaparib, n = 107; placebo, n = 54), median PFS was 6.7 vs 5.4 months, respectively (HR, 0.58 [95% CI 0.40–0.85]; P= 0.0049), and 31.8% vs 4.3% were progression-free at 1 yr. In this post hoc exploratory analysis, we further evaluated the efficacy of rucaparib maintenance vs placebo in this subset of pts. Methods: Pts were randomized 2:1 to oral rucaparib (600 mg BID) or placebo. For this analysis, investigator-assessed PFS and safety were evaluated in pts with HRD-negative carcinoma, defined as BRCA wild-type with genomic LOH < 16% using Foundation Medicine’s T5 NGS assay. Results: Visit cutoff dates for efficacy and safety were Apr 15, 2017, and Dec 31, 2019. Across subgroups based on demographic or disease characteristics, the trend of rucaparib benefit vs placebo was consistently observed in pts with HRD-negative carcinoma (Table). The safety profile of rucaparib in the HRD-negative population was consistent with that of the overall safety population reported previously. Conclusions: Rucaparib maintenance reduced risk of progression in pts with ovarian carcinomas, including those not associated with HRD, regardless of clinical prognostic factors.
Baseline Characteristic | Subcategory | HR (95% CI) | Subcategory | HR (95% CI) |
---|---|---|---|---|
Age | < 65 years (n = 86) | 0.48 (0.25–0.90) | ≥65 years (n = 75) | 0.56 (0.31–1.03) |
Race | White (n = 128) | 0.64 (0.42–0.98) | Other/unknown (n = 33) | 0.52 (0.22–1.23) |
Measurable disease at baseline | Yes (n = 66) | 0.60 (0.32–1.12) | No (n = 95) | 0.53 (0.31–0.89) |
Bulky disease at baseline | Yes (n = 36) | 0.62 (0.25–1.54) | No (n = 125) | 0.59 (0.39–0.91) |
Number of prior chemotherapy regimens | 2 (n = 112) | 0.65 (0.42–1.03) | ≥3 (n = 49) | 0.48 (0.22–1.06) |
Previous bevacizumab use | Yes (n = 40) | 0.60 (0.25–1.45) | No (n = 121) | 0.57 (0.37–0.88) |
Number of prior platinum regimens | 2 (n = 113) | 0.64 (0.41–1.00) | ≥3 (n = 48) | 0.51 (0.23–1.15) |
Time to disease progression with penultimate platinum | 6–≤12 months (n = 57) | 0.44 (0.23–0.85) | > 12 months (n = 104) | 0.66 (0.42–1.05) |
Response to last platinum | RECIST complete response (n = 56) | 0.44 (0.22–0.91) | RECIST/CA-125 partial response (n = 105) | 0.65 (0.41–1.01) |
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