Systematic review: pneumonitis with PARP inhibitors

Abstract

According to the results of a systematic review and meta-analysis reported in Gynecologic Oncology, patients treated with poly(ADP-ribose) polymerase (PARP) inhibitors have an increased risk of pneumonitis, which although rare is important to recognize because it may be severe and lift-threatening . The study searched CENTRAL, CBMdisc, clinicaltrials.gov, CNKI, Embase, PubMed and wanfang to identify 16 phase II or III randomised controlled trials involving 5771 patients which compared PARP inhibitors with placebo (n=14) or other chemotherapies (n=2). The most commonly involved drug was olaparib (n=10), followed by veliparib (n=3), niraparib (n=2) and rucaparib (n=1). The incidence of pneumonitis in PARP inhibitor recipients (0.79%) was significantly higher than the incidence in controls (0.24%; Peto odds ratio [OR] 2.68; 95% CI 1.31, 5.47; p=0.007). Pneumonitis was considered a serious adverse event in 14 of the 28 PARP inhibitor recipients. Subgroup analyses did not reveal significant between-group differences, except a lower risk in patients who received <600 mg/day of olaparib (OR 0.14; 0.01, 2.17) compared to 600 mg/day (OR 4.12; 1.68, 10.11). In addition, a retrospective disproportionality analysis involved data from the US FDA’s Adverse Event Reporting System (FAERS) database. A total of 84 cases were identified, involving olaparib (n=61), niraparib (n=20), rucaparib (n=2) and talazoparib (n=1). Median patient age was 62 years. Death occurred in 13 cases (16%). Time to pneumonitis onset was 1–588 (median 81) days; the authors note that 87% of the adverse events occurred within 6 months . PARP inhibitors were associated with significant over-reporting of pneumonitis (reporting odds ratio [ROR] 4.08; 3,29, 5.06). Olaparib was associated with the most significant pneumonitis signal (ROR 11.44; 8.88, 14.74), followed by niraparib (ROR 2.19; 1.05, 3.40); there were not enough cases involving rucaparib or talazoparib for analysis. The significant risk of pneumonitis related to PARPis versus control treatment suggested that these events might be toxicities specific to PARPis , note the authors. Considering the large difference in the onset timing of pneumonitis in the FAERS database , they add, constant vigilance for the signs and symptoms of this toxicity is required, especially during the first 6 months .