Interpretation
The GCIG considered PFS as the primary endpoint in front-line therapy for ovarian cancer, and not OS, because of the confounding effects of post-progression therapy on OS.7,21 Advances in various post-progression therapies, such as BEV,11−14,18 trientine,22 and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor,4,23−25 may help extend patients’ lives. We provided evidence while we observed a longer median OS in the BEV throughout group compared to that in GOG-218 and ICON7, even in patients who received only chemotherapy. When adjusted by multivariate analysis, our real-world findings corresponded to the GCIG consensus and emphasized the role of BEV throughout in PFS prolongation. This phenomenon is observed in the improved OS after using BEV in relapsed EOC, specifically in the platinum-sensitive subgroup.
A significantly improved PFS when adding olaparib after a response to chemotherapy plus BEV has occurred and a higher incidence of reversible grade ≥ 3 haematologic AEs were reported in the PAOLA-1 trial.26 Tewari et al. reported the reductions in risk of death for BRCA1/2-mutated or non-BRCA1/2 HRD carcinomas when compared to the wild type.9 However, BRCA/HRD testing was not predictive of BEV activity. Our patients had a shorter median PFS than that of the non-Olaparib arm in PAOLA-1 trial26 or those in real-world studies.15−17 The reason for these discrepancies may be multifactorial, including different study designs, shorter maintenance duration or lower dosage of BEV, more complex disease, or reimbursement issues in the real-world setting.
Platinum resistance is an indicator of poor prognosis, and its involved mechanism is complex.27−29 Lee et al. reported that the effectiveness of BEV-included chemotherapy was feasible but varied according to the chemotherapy partner in platinum-resistant EOC.20 A real-world small study showed PFS benefits of early BEV-added chemotherapy, but insignificant survival differences between platinum-resistant and –sensitive recurrent EOC.30 However, we provided more favourable oncologic outcomes of BEV-added relapse therapy in platinum-sensitive patients. Furthermore, CCC has been thought of as a platinum-resistant malignancy. The histological distribution of EOC in Asia is quite different from that in the West. Serous, endometrioid, and CCC histology constituted 40–50%, 15–20%, and 15–20%, respectively, of EOC in Taiwan from 2000–2008.31 Komiyama et al. reported that BEV-added front-line therapy was effective for advanced-stage clear cell carcinoma.17 However, the lack of benefits of BEV on clinical outcomes across different histologies in our study is similar to findings recorded in the ICON7 final results.10Therefore, BEV could be applied regardless of histology in either an early or advanced stage.
Haematologic AEs were the most common in BEV-included trials in EOC,7,8,11−14 while similar results were observed in our study. Its safety was also promising in our relapse therapy. The cumulative incidences of hypertension and proteinuria were associated with median cumulative BEV dosages32 or the treatment durations17 in Asian women. However, our patients had less BEV-specific incidences and lower grades of AEs. This may be related to lower dosages, or fewer treatment cycles in most patients, which were in concordance with lower incidence rates of hypertension, proteinuria, GI, or non-CNS bleeding events in the BEV throughout arm in ICON7 than that in GOG-218.7,8