The University of Texas MD Anderson Cancer Center, Houston, TX
Robert L. Coleman , Amit M. Oza , Domenica Lorusso , Carol Aghajanian , Ana Oaknin , Andrew Peter Dean , Nicoletta Colombo , Johanne I Weberpals , Andrew R. Clamp , Giovanni Scambia , Alexandra Leary , Robert W. Holloway , Margarita Amenedo , Peter C.C. Fong , Jeffrey C. Goh , David M. O'Malley , Teresa Cameron , Lara Maloney , Sandra Goble , Jonathan A. Ledermann
Background: In ARIEL3, rucaparib maintenance treatment significantly improved progression-free survival (PFS) vs placebo in all predefined, nested cohorts: BRCA mutation; BRCA mutation + wild-type BRCA/high loss of heterozygosity (LOH); and intent-to-treat (ITT) population. Methods: Pts were randomized 2:1 to receive oral rucaparib 600 mg BID or placebo. Exploratory endpoints of time to first subsequent therapy (TFST), time to investigator-assessed PFS on the subsequent line of treatment or death (PFS2), and time to second subsequent therapy (TSST) were assessed in the predefined cohorts. Results: Exploratory efficacy endpoint data are given in the Table. As of Dec 31, 2017, the most common treatment-emergent adverse events (TEAEs) of any grade (rucaparib vs placebo) were nausea (75.8% vs 36.5%), asthenia/fatigue (70.7% vs 44.4%), dysgeusia (39.8% vs 6.9%), and anemia/decreased hemoglobin (39.0% vs 5.3%). The most common grade ≥3 TEAEs were anemia/decreased hemoglobin (21.5% vs 0.5%) and alanine/aspartate aminotransferase increase (10.2% vs 0.0%). Conclusions: Rucaparib significantly improved the clinically meaningful endpoints TFST, PFS2, and TSST vs placebo in all predefined cohorts of pts with platinum-sensitive, recurrent OC. The updated safety profile was consistent with prior reports. Clinical trial information: NCT01968213
BRCA mutant | BRCA mutant or BRCA wild type/LOH high | ITT | ||||
---|---|---|---|---|---|---|
Rucaparib (n=130) | Placebo (n=66) | Rucaparib (n=236) | Placebo (n=118) | Rucaparib (n=375) | Placebo (n=189) | |
TFST | ||||||
Median, mo | 19.0 | 7.2 | 16.4 | 7.6 | 12.5 | 7.4 |
HR (95% CI); P value | 0.29 (0.20–0.42); | 0.40 (0.30–0.52); | 0.43 (0.35–0.53); | |||
P<0.0001 | P<0.0001 | P<0.0001 | ||||
PFS2 | 26.1 | 17.9 | 24.7 | 17.9 | 21.1 | 16.5 |
Median, mo | 0.44 (0.29–0.69); | 0.57 (0.41–0.79); | 0.62 (0.48–0.79); | |||
HR (95% CI); P value | P=0.0003 | P=0.0006 | P=0.0001 | |||
TSST | NR | 19.4 | 26.5 | 19.4 | 22.2 | 18.6 |
Median, mo | 0.49 (0.31–0.78); | 0.58 (0.41–0.82); | 0.70 (0.54–0.91); | |||
HR (95% CI); P value | P=0.0024 | P=0.0018 | P=0.0064 |
Visit cutoff Apr 15, 2017 (date of unblinding for primary efficacy analyses).
HRs estimated with a Cox proportional hazards model.
CI, confidence interval; HR, hazard ratio; NR, not reached.
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Abstract Disclosures
2022 ASCO Annual Meeting
First Author: Robert L. Coleman
2018 ASCO Annual Meeting
First Author: Carol Aghajanian
2023 ASCO Annual Meeting
First Author: Bradley Corr
2018 ASCO Annual Meeting
First Author: Ana Oaknin