Results
PARPi monotherapy was comparable to platinum-based chemotherapy
in patients with secondary platinum-sensitive relapse.
A total of 64 patients were eligible for this retrospective analysis,
including 31 (48.4%) in the study group and 33 (51.6%) in the control
group. The median age at diagnosis of enrolled patients was 49 years,
and the majority (75.0%) of patients had BRCA1 mutations. The baseline
characteristics of patients were shown in Table 1 and Table S1, and were
generally well balanced in age of diagnosis (p=0.599), neoadjuvant
chemotherapy followed by interval debulking surgery (NAC-IDS), FIGO
stage (p=0.645), residual lesions of primary surgery (p=0.985), CA125
level at secondary platinum-sensitive relapse (p=0.356) or primary
debulking surgery (PDS) (p=0.875), PFI after 1st(p=0.243) and 2nd (p=0.363) platinum-based
chemotherapy.
Tumor response of PARPi monotherapy and platinum-based chemotherapy was
the primary observation of this study. 28 patients (90.3%) with PARPi
monotherapy were on medication for more than 6 months, and 11 patients
(35.5%) for more than 12 months. All 31 patients in study group were
evaluable and showed excellent outcomes, with 24 patients (77.4%)
meeting the criteria for disease remission. Tumor evaluation was
available in 25 patients (75.8%) who received platinum-based
chemotherapy, and disease remission was achieved in 21 patients
(84.0%), which was comparable to PARPi monotherapy (p=0.538), and there
was no statistical difference in median PFS between the two groups
(Figure 2A; median PFS, 8.6 vs. 11.1 months, HR=0.89, p=0.679).
Due to the limitations of retrospective studies, we only collected
comparisons of hematological toxicity between the two treatments. The
incidence of hematologic toxicity ≥ 3 CTCAE was similar in both groups,
with no statistical difference (35.5% vs. 28.6%, p=0.602).
Myelodysplastic syndromes (MDS) and acute myelocytic leukemia (AML) did
not occur in patients treated with PARPi monotherapy at follow-up.
2. PARPi monotherapy after
secondary platinum-sensitive relapse significantly prolonged
post-recurrent survival.
Ten patients in control group were treated with PARPi in posterior lines
and were not included in the survival analysis.
The
median duration of post-recurrent follow-up for survival analysis was
30.0 months in PARPi monotherapy group, and 27.0 months in control
group. Treatment with PARPi monotherapy resulted in a 65% reduction in
the risk of death compared with control group (Figure 2B; HR=0.35, 95%
Cl 0.14 to 0.87, p=0.024), and the median PRS was not reached (NR) in
the PARPi monotherapy group compared with 33.3 months in the control
group.
Univariate analysis was performed, and included the following variables:
age at diagnosis, BRCA1/2 mutation status, PARPi monotherapy or not,
residual lesions (R0, no residual lesions; R1, residual lesions less
than 1 cm; R2, residual lesions more than 1 cm), FIGO stage, NAC-IDS or
PDS, CA-125 level at secondary recurrence, primary and secondary PFI,
and the results were shown in Table S2. Variables significantly
associated with PRS included PARPi monotherapy vs. platinum-based
chemotherapy (HR=0.36, 95%CI 0.15-0.92, p=0.032) and residual lesions
(R0 vs. R1/R2, HR=0.29, 95%CI 0.11-0.78, p=0.014). In the multivariate
analysis, FIGO stage at diagnosis was additionally included (I or II vs.
III or IV, HR=0.18, 95%CI 0.24-1.35, p=0.096), and the results showed
that PARPi monotherapy remained significant (HR=0.33, 95%CI 0.12-0.94,
p=0.038), whereas residual lesions (R0 vs. R1/R2, HR=0.42, 95%CI
0.15-1.17, p=0.097) and FIGO stage at diagnosis (I or II vs. III or IV,
HR=0.33, 95%CI 0.04-2.74, p=0.305) showed no statistical significance.