Abstract discussant of the NORA trial, Antonio González-Martín, MD, PhD, Director of the Department of Medical Oncology at Clinica Universidad de Navarra, Madrid, said that despite the results of this ad hoc interim analysis, “the jury is still out” regarding the overall survival benefit of PARP (poly [ADP-ribose] polymerase) inhibitors as maintenance in platinum-sensitive recurrent ovarian cancer.

Antonio González-Martín, MD, PhD

Study Limitations and Strengths

“This a nonprespecified ad hoc analysis with less than 50% of events, and no information about the predefined number of events for the preplanned overall survival was provided,” said Dr. González-Martín, commenting on the study’s limitations. “The absence of information on subsequent therapies beyond PARP inhibitors and the lack of analysis according to homologous recombination deficiency [HRD] are also worth nothing.”

On the other hand, Dr. González-Martín called the adjusted overall survival analysis for subsequent PARP inhibitor treatment a strength of the study. “This is important and necessary information, given the recent concerns about overall survival in patients with nongermline BRCA–mutated tumors treated with PARP inhibitor maintenance in relapse,” he explained.

Valid or Exploratory Endpoints

The crucial question, according to Dr. González-Martín, is whether overall survival was a real secondary endpoint or an exploratory ­endpoint.

“Considering that patients with HRD tumors should receive PARP inhibitors in the first-line setting regardless of BRCA status, overall survival should be appropriately powered to be considered a secondary endpoint,” said Dr. González-Martín. “Otherwise, it should be taken as an exploratory endpoint in maintenance trials for patients with recurrent ovarian cancer.”

According to Dr. González-Martín, however, progression-free survival, time to second disease progression, and time to second subsequent therapy are valid endpoints in recurrent ovarian cancer for making clinical decisions for individual patients. In addition, he added, these endpoints support the use of a PARP inhibitor as maintenance in second or further lines, regardless of BRCA status.

“Patients with non–BRCA-mutated tumors who are candidates to receive a PARP inhibitor as maintenance in the recurrent setting should be informed about contradictory data on overall survival and the limitations in the interpretation,” Dr. González-Martín concluded. “Clinical and translational research about the mechanisms of resistance to PARP inhibitor and the optimal therapy sequence is eagerly needed.” 

DISCLOSURE: Dr. González-Martín has reported financial relationships with Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, HederaDx, Immunogen, Illumina, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Roche, SOTIO, SUTRO, Seagen, and Takeda.