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Department of Gynecologic Oncology, the Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital & Institute, Sichuan, Cancer Center, Chengdu 610041, ChinaDepartment of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
Department of Gynecologic Oncology, the Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital & Institute, Sichuan, Cancer Center, Chengdu 610041, China
Department of Gynecologic Oncology, the Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital & Institute, Sichuan, Cancer Center, Chengdu 610041, China
Department of Gynecologic Oncology, the Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital & Institute, Sichuan, Cancer Center, Chengdu 610041, China
Department of Gynecologic Oncology, the Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital & Institute, Sichuan, Cancer Center, Chengdu 610041, China
Department of Biochemistry & Molecular Biology, the Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Chengdu 610041, China
Department of Gynecologic Oncology, the Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital & Institute, Sichuan, Cancer Center, Chengdu 610041, China
From 2019 to 2022, the proportion of PSR maintenance therapy with PARPi increased from 29.6% to 62.2%.
•
There were substantial differences between the patients in actual clinical settings and the RCTs population.
•
The mPFS was 26.1 months in a real-world study regarding PARPi maintenance therapy in recurrent ovarian cancer patients.
•
CR to the primary therapy was the independent factor favorably affecting PFS in the new treatment mode.
Abstract
Objective
To assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS).
Methods
We retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors.
Results
Between 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2–32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081–9.757, P = 0.036).
Conclusions
PARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode.
]. According to the 2020 Global Cancer Statistics, there were approximately 314,000 new cases and 207,000 deaths worldwide, whereas in China, there were approximately 55,000 new cases and 38,000 deaths [
]. Patients with early stage ovarian cancer are usually asymptomatic, and approximately 75% of them are in an advanced stage [International Federation of Gynecology and Obstetrics (FIGO) stage III–IV] when they first present with symptoms [
]; thus, the prognosis is often poor, with median progression-free survival (PFS) of 12–18 months, and five-year overall survival (OS) rate of approximately 30% [
]. There had been no meaningful improvement in >30 years.
In recent years, poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) therapy has facilitated breakthroughs in maintenance therapy for ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) and holds promise for enabling a clinical cure in some patients with advanced diseases. Study19, SOLO2, NOVA, NORA, and other randomized controlled trials (RCTs) have indicated that PARPi maintenance therapy can significantly prolong PFS and reduce the risk of disease progression or death in patients with platinum-sensitive recurrence (PSR); among them, those with BRCA mutations receive the greatest benefit [
Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.
Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial.
Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial.
]. To date, PARPi is recommended by the National Comprehensive Cancer Network (NCCN) guidelines for maintenance therapy in ovarian cancer patients with PSR after platinum-based chemotherapy has achieved complete response (CR) or partial response (PR) [
The above well-designed and standardized RCTs provide high-level medical evidence and are also an important basis for guideline recommendations and clinical practice. However, patients treated in actual clinical settings often differ from the research participants in RCTs selected by strict inclusion and exclusion criteria. The status of PARPi therapy in actual clinical settings in our hospital and how the needs of actual patients with ovarian cancer differ from those in these representative RCTs are unknown issues worthy of further discussion, and no relevant studies have been reported so far. Therefore, this study retrospectively analyzed single-center real-world clinical data, regarding PARPi maintenance therapy in patients with recurrent ovarian cancer to assess the actual clinical application and efficacy of PARPi therapy and preliminarily explore prognostic factors. It is expected that the prognosis of patients with ovarian cancer can be further improved.
2. Methods
2.1 Study design and participants
The real-world clinical data in this study were obtained from Sichuan Cancer Hospital and were seperated into two parts. Patients from different time periods were selected for various purposes.
In the first part of the study, to calculate the annual proportion of ovarian cancer patients with PSR who received PARPi maintenance therapy and dynamics of this metric, patients were selected for analysis between January 1, 2019, and May 31, 2022 (part 1 of the results below). The guideline-based criteria for patients who were suitable for PARPi maintenance therapy were as follows: (1) inclusion criteria: ovarian cancer patients with PSR who achieved CR or PR after platinum-based chemotherapy, with or without secondary cytoreduction surgery (SCS), who therefore, exhibited indications for PARPi maintenance therapy according to the 2022 version 1 NCCN guidelines [
]; patients who completed post-relapse chemotherapy in our hospital between January 1, 2019 and May 31, 2022 and patients who received a pathological diagnosis in our hospital. (2) exclusion criteria: patients who received previous PARPi treatment.
In the second part of the study, to analyze the prognosis and prognostic factors, patients were enrolled from August 2018 when the PARPi was launched in China untill December 31, 2021 (parts 2, 3, and 4 of the results below). The criteria for enrollment were as follows: (1) inclusion criteria: recurrent ovarian cancer patients who received PARPi maintenance therapy in our hospital between August 2018 and December 31, 2021 (subject to the start time of maintenance therapy) with or without SCS in the course of treatment, and patients who received a pathological diagnosis in our hospital. (2) exclusion criteria: Patients with incomplete clinicopathological data and those who received previous PARPi treatment.
2.2 Data collection
We retrieved and collected data of patients who met the inclusion and exclusion criteria of the above two parts using the electronic information system of our hospital. For patients who had received PARPi maintenance therapy, the relevant clinicopathological data were collected, including age, body mass index (BMI), primary tumor site, FIGO stage at diagnosis, pathological type, BRCA status, primary treatment [neoadjuvant chemotherapy (NACT), residual disease size after surgery, time of last chemotherapy, and response to primary therapy], recurrence time, post-recurrence treatment, and PARPi maintenance therapy. No visible residual disease after surgery was defined as R0, residual disease < 1 cm after surgery was defined as R1, and residual disease ≥ 1 cm after surgery was defined as R2. Response evaluation was performed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or CA125 levels. The patients were divided into olaparib and the niraparib groups according to the type of PARPi used.
2.3 Follow-up
All the enrolled patients were followed up until May 7, 2022, or death. PFS was defined as the time from the end of post-relapse chemotherapy to disease progression or the end of follow-up (non-relapse).
2.4 Statistical analysis
Statistical analyses were performed using SPSS version 25.0. Continuous variables with normal distribution were reported as mean ± standard deviation, and independent t-tests or one-way ANOVA were used for comparison. For continuous variables with non-normal distribution, the median [interquartile range (IQR)] was used for statistical description, and comparisons were performed using the Mann–Whitney U test or Kruskal–Wallis H test. Categorical variables were presented as frequencies and percentages [n (%)], and chi-square tests were used for comparisons between the groups. Univariate and multivariate analyses of PFS were conducted using the Cox proportional hazard model. Kaplan-Meier curves were created to assess clinicopathological variables and their associations with PFS. A log-rank (Mantel–Cox) test was used to compare the PFS. Results with P values < 0.05 were considered statistically significant.
3. Results
3.1 PARPi maintenance therapy in ovarian cancer patients with PSR
Between January 1, 2019, and May 31, 2022, 142 ovarian cancer patients with PSR who completed platinum-based chemotherapy and achieved CR or PR met the indications for PARPi maintenance therapy recommended by the NCCN guidelines in our hospital. Among them, 68 (47.9%, 68/142) patients received PARPi maintenance therapy, of which eight (29.6%, 8/27), 16 (53.3%, 16/30), 21 (43.8%, 21/48), and 23 (62.2%, 23/37) received PARPi maintenance therapy in 2019, 2020, 2021, and 2022 (January to May), respectively.
3.2 Real-world clinical data on PARPi maintenance therapy in patients with recurrent ovarian cancer
Between August 2018 and December 31, 2021, a total of 48 patients with recurrent ovarian cancer received PARPi maintenance therapy, including 40 with ovarian cancer, four with fallopian tube cancer, and four with primary peritoneal cancer. The median follow-up time was 17.8 months (IQR, 12.9–21.9), with no loss to follow-up. Patients were 53.3 ± 7.9 years old, the number of post-relapse chemotherapy courses was 6 (5–8), and the interval between the last chemotherapy and maintenance therapy was 40.5 days (IQR, 30.3–56.0). The clinicopathological data of the patients is presented in Table 1.
Table 1Comparison of clinicopathological characteristics between the two groups of patients.
Non-HGSC included 2 cases of high-grade endometrioid carcinoma, 1 case of low-grade serous carcinoma, 1 case of serous carcinoma with unknown grade, and 5 cases of adenocarcinoma (specific type unknown).
9 (18.8)
6 (18.8)
3 (18.8)
BRCA status [n (%)]
χ2 = 9.075
0.011
BRCA mutation
11 (22.9)
10 (31.3)
1 (6.3)
BRCA wild-type
22 (45.8)
10 (31.3)
12 (75.0)
Unknown
15 (31.3)
12 (37.5)
3 (18.8)
NACT at primary treatment [n (%)]
χ2 = 0.000
1.000
Yes
21 (43.8)
14 (43.8)
7 (43.8)
No
27 (56.3)
18 (56.3)
9 (56.3)
Residual disease after primary surgery [n (%)]
χ2 = 4.486
0.214
R0
20 (41.7)
13 (40.6)
7 (43.8)
R1
12 (25.0)
7 (21.9)
5 (31.3)
R2
5 (10.4)
5 (15.6)
0 (0.0)
Unknown
11 (22.9)
7 (21.9)
4 (25.0)
Response to primary platinum-based chemotherapy [n (%)]
χ2 = 0.000
1.000
CR
21 (43.8)
14 (43.8)
7 (43.8)
PR
16 (33.3)
11 (34.4)
5 (31.3)
Unknown
11 (22.9)
7 (21.9)
4 (25.0)
PFI [n (%)]
χ2 = 0.496
0.781
< 6 months
7 (14.6%)
4 (12.5%)
3 (18.8%)
6 ∼ < 12 months
17 (35.4%)
11 (34.4%)
6 (37.5%)
≥ 12 months
24 (50.0%)
17 (53.1%)
7 (43.8%)
Previous lines of chemotherapy [n (%)]
–
0.551
2
31 (64.6)
20 (62.5)
11 (68.8%)
3
6 (12.5)
5 (15.6)
1 (6.3)
≥ 4
11 (22.9)
7 (21.9)
4 (25.0)
SCS [n (%)]
χ2 = 0.269
0.604
Yes
11
9 (28.1)
2 (12.5)
No
37
23 (71.9)
14 (87.5)
Residual disease after SCS [n (%)]
χ2 = 0.000
1.000
R0
9 (81.8)
7 (77.8)
2 (100.0)
R1
2 (18.2)
2 (22.2)
0 (0.0)
Bevacizumab [n (%)]
χ2 = 1.505
0.220
Yes
17 (35.4)
13 (40.6)
4 (25.0)
No
31 (64.6)
19 (59.4)
12 (75.0)
Chemotherapy cycles for this recurrence [n (%)]
6 (5–8)
6 (5–8)
7 (6–8)
Z = -0.935
0.350
Response to platinum-based post-relapse chemotherapy [n (%)]
One case of PARPi therapy discontinuation due to acute myeloid leukemia.
1 (2.1)
1 (3.1)
0 (0.0)
χ2 = 0.00
1.000
BMI: body mass index; FIGO: International Federation of Gynecology and Obstetrics; HGSC: high-grade serous carcinoma; non-HGSC: nonhigh-grade serous carcinoma; NACT: neoadjuvant chemotherapy; R0: no visible residual disease after surgery; R1: residual disease after surgery < 1 cm; R2: residual disease after surgery ≥ 1 cm; CR: complete response; PR: partial response; PFI: platinum-free interval; SCS: secondary cytoreduction surgery; ICM: the interval between the last chemotherapy and maintenance therapy; PARPi: poly (adenosine diphosphate-ribose) polymerase inhibitor.
a Non-HGSC included 2 cases of high-grade endometrioid carcinoma, 1 case of low-grade serous carcinoma, 1 case of serous carcinoma with unknown grade, and 5 cases of adenocarcinoma (specific type unknown).
b After re-evaluation, there were 3 patients with stable disease and 1 patient with progressive disease.
c One case of PARPi therapy discontinuation due to acute myeloid leukemia.
Among the 48 patients, 32 were in the olaparib group and 16 were in the niraparib group. There was a significant difference in BRCA status between the two groups (P < 0.05). In the olaparib group, 31.3% of the patients had BRCA mutations, and 31.3% were BRCA wild-type; in the niraparib group, 6.3% had BRCA mutations, and 75.0% were BRCA wild-type, as shown in Table 1.
3.3 Assessments using the inclusion and exclusion criteria of the Study19, SOLO2, NOVA, and NORA studies
Among the 32 patients in the olaparib group, only 18 (56.3%) and 6 (18.8%) met the inclusion and exclusion criteria of the study19 and SOLO2 studies, respectively. Among the 16 patients in the niraparib group, only five (31.3%) and six (37.5%) patients met the inclusion and exclusion criteria of the NOVA and NORA studies, respectively. See Table 2 for details.
Table 2Analysis of real-world clinical data regarding PARPi maintenance therapy for recurrent ovarian cancer in our hospital using the inclusion and exclusion criteria of representative RCTs.
Inclusion and exclusion criteria of RCTs
Comparison with real-world clinical data in our hospital
Maintenance therapy started > 8 weeks after chemotherapy
HGSC or high-grade serous carcinoma
6 (18.8)
Two patients with high-grade endometrioid carcinoma, one with low-grade serous carcinoma, and three patients with adenocarcinoma (specific type unknown)
Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.
Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial.
Among the 48 patients, 20 (41.7%) exhibited disease progression, and one (2.1%) died during the follow-up period with a median treatment time of 12.1 months (IQR, 6.6–16.6), and a median PFS (mPFS) of 26.1 months (95% CI 20.2–32.1). One patient developed acute myeloid leukemia (AML), and no patient had myelodysplastic syndrome (MDS).
Univariate analysis showed that BRCA status, residual disease after primary surgery, and response to primary therapy were significantly correlated with PFS (P < 0.05). See Table 3 and Fig. 1. These three indicators were included in the multivariate Cox regression analysis, and the results showed that response to primary therapy was an independent factor affecting PFS in patients with recurrent ovarian cancer who received PARPi maintenance therapy (relative risk, 3.248; 95% CI 1.081–9.757, P = 0.036).
Table 3Results of univariate analysis of factors affecting PFS.
Non-HGSC included two cases of high-grade endometrioid carcinoma, one case of low-grade serous carcinoma, one case of serous carcinoma with unknown grade, and five cases of adenocarcinoma (specific type unknown).
9
27.1
21.0–33.2
BRCA status
7.698
0.021
BRCA mutation
11
41.1
34.9–47.2
BRCA wild-type
22
26.5
17.8–35.2
Unknown
15
14.2
9.5–18.8
NACT at primary treatment
0.000
0.990
Yes
21
26.5
18.2–34.8
No
27
26.4
18.2–34.7
Residual disease after primary surgery
6.785
0.034
R0
20
31.2
22.6–39.7
R1
12
34.0
23.7–44.3
R2
5
12.4
5.5–19.4
Response to primary therapy
4.921
0.027
CR
21
34.2
26.4–41.9
PR
16
16.1
10.8–21.4
PFI
1.198
0.549
< 6 months
7
17.3
8.3–26.4
6 ∼ < 12 months
17
27.2
17.3–37.1
≥ 12 months
24
25.9
17.2–34.7
SCS
0.897
0.343
Yes
11
30.4
19.9–40.8
No
37
20.0
15.7–24.3
Residual disease after SCS
2.020
0.155
R0
9
32.4
21.8–43.0
R1
2
9.7
5.4–14.0
Bevacizumab
1.316
0.251
Yes
17
21.5
12.2–30.7
No
31
28.5
20.9–36.1
Chemotherapy cycles for this recurrence
2.924
0.232
< 6
13
31.9
21.8–42.0
6–9
27
25.2
17.2–33.2
> 9
8
14.4
7.3–21.4
Response to platinum-based post-relapse chemotherapy
After re-evaluation, there were three patients with stable disease and one patient with progressive disease.
4
12.9
8.1–17.7
ICM
7.547
0.056
≤ 4 weeks
12
15.9
12.6–19.2
4–6 weeks
13
23.3
16.6–30.0
6–8 weeks
12
18.8
8.6–28.9
> 8 weeks
11
30.3
20.4–40.1
PFS: progression-free survival; HGSC: high-grade serous carcinoma; non-HGSC: nonhigh-grade serous carcinoma; FIGO: International Federation of Gynecology and Obstetrics; NACT: neoadjuvant chemotherapy; R0: no visible residual disease after surgery; R1: residual disease after surgery < 1 cm; R2: residual disease after surgery ≥ 1 cm; CR: complete response; PR: partial response; PFI: platinum-free interval; SCS: secondary cytoreduction surgery; ICM: the interval between the last chemotherapy and maintenance therapy.
a Non-HGSC included two cases of high-grade endometrioid carcinoma, one case of low-grade serous carcinoma, one case of serous carcinoma with unknown grade, and five cases of adenocarcinoma (specific type unknown).
b After re-evaluation, there were three patients with stable disease and one patient with progressive disease.
Fig. 1Kaplan–Meier analysis of PFS. (A) Residual disease after primary surgery (R0/R1/R2); (B) Response to primary therapy (CR/PR); (C) BRCA status (BRCA mutation/BRCA wild-type/BRCA unknown).
4.1 Concept of PARPi maintenance therapy and the increasing acceptance by doctors and patients
The advent of PARPi has changed the treatment mode of ovarian cancer from surgery combined with chemotherapy to a strategy involving surgery, chemotherapy, and maintenance therapy, which is a major breakthrough in the treatment of advanced ovarian cancer and is of great importance. In November 2017, PARPi maintenance therapy was first recommended by the NCCN guidelines for patients with PSR ovarian cancer who achieved CR or PR following platinum-based chemotherapy. However, the application of PARPi in clinical practice is limited by several factors. With the approval of PARPi in China, the reduction in prices and gradual inclusion of PARPi in the National Medical Insurance List, the availability of drugs has been improved. Clinicians have gradually improved the concept of PARPi maintenance therapy and whole-process management, and the acceptance of this approach by patients and their families has also been greatly improved. Data obtained from our provincial cancer hospital between 2019 and 2022 showed that the proportion of PSR ovarian cancer patients receiving PARPi maintenance therapy has increased to 29.6%, 53.3%, 43.8%, and 62.2%, respectively, each year, which was significantly higher than the proportion of patients who received first-line PARPi maintenance therapy in our hospital (7.0%, 20.0%, 30.8%, and 41.5%, respectively) [
]. However, there is still room for further efforts to improve the prognosis of patients with ovarian cancer.
4.2 Criteria for assessing PSR and platinum-resistant recurrence (PRR)
To date, there are still certain limitations and uncertainties in determining the type of recurrent ovarian cancer (PSR or PRR) based on platinum-free interval (PFI) alone. Most patients with disease progression within six months after PR are classified as PRR, but strictly speaking, they do not fully meet the definition of PRR in the NCCN guidelines: progression on primary, maintenance, or recurrence therapy or stable or persistent disease (if not on maintenance therapy) or CR and relapse < 6 months after completing chemotherapy. Our previous study revealed that at least 50% of patients who relapsed < 6 months after completing chemotherapy responded to platinum-based chemotherapy [
]. Additionally, the NCCN guidelines indicate that the definitions of PSR and PRR are imprecise, and that clinical judgment and flexibility should be utilized in determining treatment options [
]. In this study, seven patients had a PFI of < 6 months, of which three had only PR, two had an unknown status after the primary therapy, four had a PFI of > 5 months, one had a BRCA mutation, and all seven achieved CR (3/7) or PR (4/7) after platinum-based chemotherapy. In this study, at the end of follow-up, the PFS of seven patients was 32.1 months (no disease progression), 7.4 months (no disease progression), 14.5 months [progressive disease, (PD)], 18.7 months (no disease progression), 7.1 months (PD), 10.0 months (PD), and 3.3 months (PD) with no deaths recorded. Regardless of disease progression, PARPi maintenance therapy prolonged PFS in 85.7% (6/7) of the patients whose PFI was < 6 months. Therefore, in complex clinical practice, there are still some patients whose conditions are not defined in the guidelines. The high risk of recurrence in these patients suggests the need to explore maintenance therapy.
4.3 Prognostic factors for PFS
In this study, BRCA status and residual disease after primary surgery were potential factors affecting PFS. The mPFS in patients with optimal cytoreduction (R0 and R1) during primary surgery was significantly longer than that in those with R2 cytoreduction (31.2, 34.0, and 12.4 months, respectively, P < 0.05); the mPFS in patients with BRCA mutations, BRCA wild-type, and unknown BRCA status was 41.1, 26.5, and 14.2 months, respectively (P < 0.05). The proportion of patients with unknown BRCA status in the olaparib group was relatively high. It might be because PSR maintennance therapy didn't depend on BRCA mutations. Among the 12 patients with unknown BRCA status in the olaparib group, two achieved CR and 10 achieved PR after platinum-based post-relapse chemotherapy. Five patients were still in maintenance therapy without PD, with PFS ranging between 13.1 and 28.6 months untill the endpoint of follow-up. Seven patients exhibited PD, with PFS ranging between 3.4 and 19.3 months with no deaths recorded. However, multivariate Cox regression analysis showed that they were not independent factors affecting PFS (P > 0.05), which may be due to the small sample size and needs further research for confirmation. Achieving CR during primary therapy was an independent factor that favorably affected PFS, and the mPFS was 18.1 months longer in patients who achieved CR than in PR patients (34.2 and 16.1 months, respectively). These results indicate the important role of primary therapy for ovarian cancer in the long-term prognosis of patients, and other studies have arrived at similar conclusions. Hanker et al. conducted a survival analysis of 1620 ovarian cancer patients from three large phase III RCTs and found that even after multiple recurrences, achieving R0 at the time of primary surgery was an independent prognostic factor for recurrent ovarian cancer [
]. Hilal et al. analyzed 360 patients who were long-term survivors of recurrent ovarian cancer (survival > 5 years after recurrence) and found that optimal cytoreduction during the primary surgery was one of their common characteristics [
]. However, it is a very complicated problem in the SOLO studies, with the SOLO1 study reporting the opposite of SOLO2 study where CR predicted a more favorable effect on prognosis [
965P-evaluation of tumour responses and olaparib efficacy in platinum-sensitive relapsed ovarian cancer (PSROC) patients (pts) with or without measurable disease in the SOLO2 trial (ENGOT Ov-21).
], which is similar to our findings. In contrast, the SOLO1 study showed that the benefit of olaparib was substantially better in those with PR than in those with CR [
], and there are likely situational influences on the ‘need’ and ‘opportunity’ for benefit in different populations.
4.4 AML and MDS
In the real world analysis of postmarketing surveillance data, PARPi increases the risk of AML and MDS, which can result in high mortality and tend to ocurr during long-term use [
Myelodysplastic syndrome/acute myeloid leukemia following the use of poly-ADP ribose polymerase (PARP) inhibitors: a real-world analysis of postmarketing surveillance data.
]. It is reported that AML or MDS occured in 0.5–2.2% of patients who received PARPi maintenance therapy, and the rates in the frontline maintenance studies were similar to the recurrence maintenance studies [
Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial.
Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial.
Myelodysplastic syndrome/acute myeloid leukemia following the use of poly-ADP ribose polymerase (PARP) inhibitors: a real-world analysis of postmarketing surveillance data.
]. In this study, the incidence of AML was 2.1% (1/48). One patient developed AML seven months after starting olaparib maintenance therapy.
Although the sample size of this single-center study was small, this is the first real-world study of olaparib and niraparib as maintenance therapy among Chinese patients with recurrent ovarian cancer. We conclude that, PARPi maintenance therapy was also effective in real world applications of our patients with recurrent ovarian cancer; in the new treatment mode, particular attention should be paid to the primary treatment of ovarian cancer patients. NACT does not seem to affect the PFS of recurrent patients, but efforts to optimize cytoreduction during primary surgery and improve the CR rate have important implications for the long-term prognosis of patients. Multiple RCTs have demonstrated the efficacy of PARPi therapy and established its key role in ovarian cancer maintenance therapy. However, owing to the strict inclusion and exclusion criteria used in RCTs and objective limitations of genetic testing in China, the situations of patients treated by clinicians in actual clinical practice are quite different from those involved in RCTs; therefore, the results of this retrospective study still have meaningful clinical value.
Ethics statement and informed consent statement
This study was conducted in accordance with ethical principles and approved by the Institutional Research Ethics Committee of the Sichuan Cancer Hospital (ethical approval No. scchec-02-2022-088). Patient consent was exempted by approval of the ethics committee.
CRediT authorship contribution statement
Deng-Feng Wang: Conceptualization, Data curation, Formal analysis, Investigation, Writing – original draft, Writing – review & editing. Xun-Wei Shi: Data curation, Formal analysis, Investigation, Writing – original draft, Writing – review & editing. Can Zhang: Data curation, Investigation. Jie Zhang: Data curation, Investigation. Hong Liu: Data curation, Formal analysis, Investigation. Jian-Ming Huang: Conceptualization, Investigation, Writing – review & editing. Guo-Nan Zhang: Conceptualization, Investigation, Supervision, Writing – original draft, Writing – review & editing. Qing-Lian Wen: Conceptualization, Investigation, Supervision, Writing – review & editing.
Declaration of Competing Interest
The authors have no conflict of interest to declare.
Acknowledgement
This study was supported by Sichuan Province Key Discipline Funding from the hospital (No. YB2013052).
Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.
Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial.
Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial.
965P-evaluation of tumour responses and olaparib efficacy in platinum-sensitive relapsed ovarian cancer (PSROC) patients (pts) with or without measurable disease in the SOLO2 trial (ENGOT Ov-21).
Myelodysplastic syndrome/acute myeloid leukemia following the use of poly-ADP ribose polymerase (PARP) inhibitors: a real-world analysis of postmarketing surveillance data.
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