Ana Oaknin, MD, PhD, Head of the Gynecologic Cancer Program at Vall d’Hebron Institute of Oncology, Barcelona, discussed the PRIMA/ENGOT-OV26/GOG-3012 trial along with the results of the phase III PAOLA-1/ENGOT-ov25 trial of olaparib plus bevacizumab maintenance. According to Dr. Oaknin, the positive results reported at the European Society for Medical Oncology Congress 2019 for poly (ADP-ribose) polymerase (PARP) inhibitors as maintenance therapy translate into “a paradigm shift in the first-line treatment of ovarian cancer.”
Ana Oaknin, MD, PhD
All three trials—PRIMA, PAOLA-1, and VELIA/GOG-3005, which evaluated veliparib—demonstrated statistically significant and clinically meaningful benefits in progression-free survival, with some suggestion of an overall survival benefit also observed. Despite the similarities among the studies, their populations and induction regimens were different, so Dr. Oaknin cautioned against comparing the results. Of note, in the PRIMA trial, virtually all patients with stage III disease had visual residual disease after surgery, and 35% had stage IV disease. Hazard ratios are more relevant for comparison, she commented.
Benefit for All Biomarker Subgroups
The benefit with niraparib was observed across all biomarker subgroups. As in the other trials, the magnitude of benefit was greatest in the BRCA-mutated population (hazard ratio = 0.40), although patients with BRCA wild-type disease also benefited (hazard ratio = 0.50). “The results in patients with HRD [homologous recombination deficiency] lacking a BRCA mutation identify a new population who could significantly benefit from treatment with niraparib,” Dr. Oaknin stated.
As a prespecified exploratory endpoint, all the trials examined the benefit of PARP inhibitors in HRD-negative (ie, HRD-proficient) patients, which comprised 34% of the PRIMA population and (with HRD-unknown status) 52% of women in PAOLA-1. It is interesting to note that only in the PRIMA trial did the PARP inhibitor reduce the risk of disease progression in HRD-negative patients (hazard ratio = 0.68); this was not observed in PAOLA-1 (hazard ratio = 0.92) or VELIA/GOG-3005 (hazard ratio = 0.80).
Dr. Oaknin did express some concern about the rate of dose reductions (71%) and dose interruptions (79%) in patients receiving niraparib. However, she acknowledged, just 12% of this arm discontinued treatment due to toxicity.
Based on the results of PRIMA, PAOLA-1, and VELIA/GOG-3005, Dr. Oaknin shared these concluding remarks: “The benefit of adding a PARP inhibitor as maintenance therapy to first-line treatment is clinically meaningful enough to justify its use as a new standard of care. Although the benefit is clinically meaningful in the overall population, we should consider progression-free survival outcomes, according to the biomarker status, in the selection of optimal therapy. For this, a companion diagnostic test will be needed.”
DISCLOSURE: Dr. Oaknin has served as a consultant as well as served on the speakers bureau for or received travel funding from AstraZeneca, Clovis Oncology, ImmunoGen, PharmaMar, Roche, and Tesaro.
In women with advanced ovarian cancer responding to first-line chemotherapy, maintenance therapy with the PARP inhibitor niraparib significantly reduced the risk of disease progression by 38% overall and by 60% in women with BRCA mutations. Even patients without a homologous recombination...