Safety and Efficacy Results of Retreatment With a PARP Inhibitor Monotherapy in Late-Line Recurrent Ovarian Cancer: Results From a Subset of the QUADRA Trial

Abstract

OBJECTIVES: Promising data in the front- and second-line settings are moving the use of poly(ADP-ribose) polymerase inhibitors (PARPi) earlier in the treatment of ovarian cancer (OC); thus, data on PARPi retreatment have increasing clinical relevance. It remains unknown whether patients (pts) who discontinue PARPi treatment for disease progression or other reasons (eg, planned fixed duration, adverse events [AEs], treatment fatigue) will experience different tumor response upon re-exposure. Here, we present safety and efficacy data from the subset of pts with prior PARPi exposure before niraparib monotherapy for late-line recurrent OC in the QUADRA trial (NCT02354586). METHODS: Eligible pts had recurrent serous OC and ≥3 prior lines of chemotherapy. Pts with prior PARPi exposure (niraparib, rucaparib, olaparib, or veliparib) in any setting were eligible to enroll. Pts received niraparib 300 mg once daily until disease progression. Treatment-emergent AEs (TEAEs) were managed with dose reduction to 200 or 100 mg daily. The primary endpoint was overall response rate per RECIST v1.1. RESULTS: Of 463 treated pts on this trial, 37 had prior PARPi exposure (monotherapy, n=26; combination therapy, n=11). Thirty-three pts discontinued prior PARPi due to disease progression and 4 for other reasons. Overall, 35 pts had evaluable response data; 1 pt (3%) had a confirmed partial response, and 12 (34%) had stable disease for at least 7 weeks. Clinical benefit rate at 16 weeks was 20%. Figure 1 shows the change in tumor size over time. Of note, among the 4 pts who had not progressed during prior PARPi treatment, 1 pt had a clinical response that did not meet RECIST criteria (normalization of elevated CA-125 levels and baseline tumor no longer observed). Table 1 shows safety data. CONCLUSIONS: This analysis demonstrates the safety of PARPi retreatment, as TEAEs did not increase among pts with prior PARPi exposure as compared with PARPi-naïve pts. In this small dataset of pts with heavily pretreated recurrent OC, pts who progressed on prior PARPi gained limited benefit from subsequent PARPi monotherapy. However, future studies should address unanswered questions such as (1) the efficacy of PARPi retreatment among pts who discontinue PARPi treatment for reasons other than progression, (2) whether another PARPi can be safely re-administered after discontinuation for toxicity, and (3) if PARPi resistance can be overcome by a PARPi-free interval or with combination therapy. LEARNING OBJECTIVES: Learners will be able to identify critical questions related to PARPi retreatment. ATTACHMENT: On next page [Formula presented] [Formula presented]