In the world of PARP inhibition, the battle between AstraZeneca/Merck & Co’s (AZ/MSD) Lynparza and GlaxoSmithKline’s (GSK) Zejula now rages as fiercely as the infamous and ongoing battle in the immunotherapy world between Bristol-Myers Squibb’s Opdivo and Merck & Co’s Keytruda.
On 29 April 2020, the FDA approved Zejula for maintenance therapy in advanced ovarian, fallopian tube, or primary peritoneal cancer patients who are in complete or partial response to frontline platinum-based chemotherapy. With the FDA granting priority review designation in January 2020 to a supplemental new drug application (sNDA) for Lynparza in this same setting, a decision is now imminent.
FDA approval for Zejula is based on the placebo-controlled Phase III trial known as PRIMA, whereby GSK’s drug demonstrated a progression-free survival (PFS) of 13.8 months versus 8.2 months in the placebo arm. Subset analyses have shown that in homologous recombination deficient (HRD)-positive patients, PFS is 21.9 months in the Zejula arm versus 10.4 months in the placebo group.
The sNDA for Lynparza is based on the Phase III trial known as PAOLA-1, which combines AZ/MSD’s drug with bevacizumab, the previous standard of care for high-risk patients in this setting, and compares it to bevacizumab alone. Subset analyses have shown that in HRD-positive patients, PFS is 37.2 months in the Lynparza + bevacizumab arm versus 17.7 months with bevacizumab alone.
Lynparza was already well-entrenched in the first-line maintenance setting for patients who harbour BRCA1/2 mutations, following FDA approval in 2018 off the back of the placebo-controlled Phase III SOLO-1 study in this setting. At 41 months, median PFS had not been reached in the Lynparza arm of the trial and was at 14.1 months in the placebo arm.
Zejula’s recent approval has given GSK the competitive edge in the frontline treatment setting, as it is independent of biomarker status. The approval of this drug based on all-comers means Zejula can be administered to a much wider population of patients in the maintenance setting. Of note, BRCA-positive patients—for which Lynparza was indicated based on SOLO-1 data—account for around 20% of patients in the first-line maintenance setting.
Despite being well-entrenched in the first-line maintenance setting and showing arguably better clinical outcomes (PFS) in HRD-positive patients compared with Zejula, Lynparza will face stiff competition from GSK’s PARP inhibitor. Further, decision-makers will need to weigh the benefit of prescribing bevacizumab in addition to AZ/MSD’s PARP inhibitor and determine which patients will benefit most from this combination versus PARP inhibitor alone or bevacizumab alone.