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