Abstract
Olaparib showed good efficacy and tolerability in the maintenance treatment of patients with initial therapy or high-grade serous recurrent ovarian cancer patients. This study aimed to analyze adverse events (AEs) of patients taking Olaparib and the quality of life (QoL) with Olaparib in 1 center of China. The study included 98 patients who received Olaparib and 210 patients without Olaparib from July 2018 to October 2021 for high-grade serous ovarian cancer in the Gynecology Oncology Department of Jiangsu Provincial Hospital. Information of clinicopathologic characteristics was collected from medical records. Then, we used the QLQ-C30 and Quality of Life Ovarian Cancer 28 Questionnaire (QLQ-OV28) to determine the QoL of 98 patients with and 210 patients without Olaparib. Among all 98 patients with Olaparib, 66 patients in first-line and 32 patients in more than second-line treatment. Regarding the best objective response with Olaparib maintenance in 78 patients with partial remission from most recent chemotherapy, 3 (3.84%) patients showed complete response (CR) and 6 (7.69%) showed as partial response (PR), whereas stable disease was observed in 42 patients (53.84%) and 27 patients (34.6%) showed as progression disease. AEs of Grade 3 and more were: anemia in 16 patients (16.32%), neutropenia in 20 patients (20.40%), thrombocytopenia in 4 patients (4.08%), and headache in 4 patients (4.08%). Dose reduction and drug discontinuation accounted for 73.40% and 20.40%, respectively. Olaparib as maintenance therapy increased QoL on all functioning domains and several symptom domains. Consistent with previous clinical trials, Olaparib maintenance therapy was proved safe and effective. Most patients may experience Grade 1 and 2 AEs. Olaparib maintenance therapy can increase QoL in several domains.
Keywords: adverse effects, HGSOC, maintenance therapy, Olaparib, QoL
1. Introduction
Ovarian cancer is the gynecological malignancy with a high fatality rate, and 70% of ovarian cancer patients are in the advanced stage when diagnosed.[1] Olaparib (Lynparza), as a poly ADP-ribose polymerase inhibitor (PARPi), can lead to synthetic lethality in BRCA1/2-deficient tumor cells.[2,3] PARPi is recommended for the maintenance treatment of patients with platinum-sensitive recurrent ovarian cancer, and those with complete response (CR) or partial response (PR) after first-line platinum containing chemotherapy and has been included in the National Medical Insurance of China since January 2022, which could significantly prolong the progression free survival (PFS) of ovarian cancer patients.[4,5]
Safety data from previous trials have demonstrated the generally good tolerance of Olaparib monotherapy among platinum-sensitive recurrent ovarian cancer patients,[6,7] suggesting the feasibility of long-term use of Olaparib as maintenance monotherapy. Yet, the tolerance of Olaparib in real-world practice might differ from clinical trials since most patients in the clinical trials were European and American populations, and few Chinese patients were included. Meanwhile, the QoL of PARPi patients has rarely been reported. This study conducted Quality of Life 30 Questionnaire and Quality of Life Ovarian Cancer 28 Questionnaire (QLQ-OV28) surveys among 80 patients who took Olaparib and 192 patients without Olaparib, hoping to tease out the safety and QoL of the PARPi.
2. Materials and methods
2.1. Patients and study design
The present retrospective study included 98 patients with Olaparib and 210 patients without Olaparib who were diagnosed and treated in Jiangsu Provincial Hospital from July 2018 to October 2021. All patients included met the following criteria: having achieved CR or PR after first-line platinum-based chemotherapy and received Olaparib as maintenance therapy, regardless of BRCA1/2 mutation status; with histologically confirmed platinum-sensitive high-grade serous recurrent ovarian cancer, having undergone a minimum of 2 previous lines of platinum-based chemotherapy, in objective response (either CR or PR) to their most recent regimen, and having platinum-sensitive disease after the penultimate line of chemotherapy, regardless of BRCA1/2 mutation status.
This study was approved by the institutional review board of the participating center (The First Affiliated Hospital of Nanjing Medical University) and strictly abided by the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.
2.2. Treatment and study assessments
Olaparib maintenance monotherapy (300 mg bid, tablets) was given orally and continued until disease progression in case of manageable toxicity. The dosage could be modified at the clinicians’ instructions. Patients were recommended to visit each month for prescriptions, symptom examination, and laboratory tests (weekly blood test during the first 3 months to complete blood count with white blood cell differential counts; monthly liver function test, renal function test, and CA-125 test) and at every 3 months for cancer evaluation (imaging examinations, mostly computed tomography scan) until objective disease progression or intolerable toxicity.
Safety and tolerability were evaluated all through the follow-up by using medical records of adverse events (AEs; graded using CTCAE v5.0), physical examination results, vital signs, and laboratory results. Endpoints of this study included safety, tolerability, duration of, and reasons for discontinuing therapy and objective response.[8]
2.3. Quality of life questionnaire
QLQ-C30 and QLQ-OV28 were used to determine the relationship between QoL in each category, and key demographic and clinical factors. Altogether 272 patients (including 80 patients with Olaparib and 192 without Olaparib) completed both the baseline and follow-up surveys and changes in QoL outcomes were determined.
2.4. Statistical analysis
Summary statistics were used to describe patient characteristics. Median (range) or mean (standard deviation) were used for continuous variables. Categorical variables are presented as frequency (percentage). The Kaplan–Meier method was used to estimate PFS and OS. To perform the analysis, SPSS software version 23.0 was used.
The EORTC QLQ-C30 and QLQ-OV28 scales were linearly transformed to continuous scales (0–100) according to the scoring EORTC scoring procedures. Missing data were imputed, using linear regression for continuous variables in line with the EORTC instructions. Totals for all scales and the summary score were calculated. Descriptive statistics were used to report population characteristics and the HRQOL outcomes. Categorical variables were presented as numbers and percentages and continuous variables were described using the median and the interquartile range.
3. Results
3.1. Patient characteristics
The baseline characteristics of the 98 patients taking Olaparib and 210 patients without Olaparib are summarized in Table 1. The With Olaparib patients group ranged in age from 36 to 73 years old, with an average age of 53.34 years, meanwhile the Without Olaparib group patients’ age ranged from 34 to 72 years old, which were basically consistent with the average age at onset of ovarian cancer. Patients with International Federation of Gynecology and Obstetrics stage III at initial diagnosis were 89.79% and 80.95% in different groups, respectively. Of the 98 ovarian cancer patients With Olaparib, nearly half (46.93%) underwent primary debulking surgery, and 81.63% patients (of all operations) achieved R0 satisfactory tumor reduction. At the same time, the PDS rate of patients The Without Olaparib group had a similar trend, however, the R0 rate (66.67%) had a lower trend comparing to the corresponding group. CA125 levels varied in all patients before initial treatment, with values ranging from 40.6 to 10,488 IU/L (mean = 1425.45 IU/L) in the With Olaparib group while the values ranging from 89 to 15,944 IU/L (mean = 1689.42 IU/L) in the Without Olaparib group. A total of 10.20% of the With Olaparib group and 4.76% of the Without Olaparib group had a family history of breast and ovarian cancer. Platinum-free interval duration more than 12 months was observed in 46 patients (46.93%) with PARPi, and the corresponding data was 47.61% patients in the Without Olaparib group. As for objective response to most recent chemotherapy in the With Olaparib group, CR was found in 64 (65.30%) patients and PR in 32 (32.65%) patients. However, in the Without Olaparib group, the CR and PR patients’ number was 100 (47.61%) and 75 (35.71%).
Table 1.
Baseline characteristics of patients.
| Characteristics | With Olaparib | Without Olaparib | P |
|---|---|---|---|
| N = 98 | N = 210 | ||
| Age, yr | 53.34 (36–73) | 54.21 (34–72) | .207 |
| Initial FIGO stage, n (%) | <.001 | ||
| I–II | 0 | 30 (14.28) | |
| IIIA | 8 (8.16) | 25 (11.90) | |
| IIIB | 2 (2.04) | 5 (2.38) | |
| IIIC | 78 (79.59) | 140 (66.67) | |
| IVA | 4 (4.08) | 5 (2.38) | |
| IVB | 6 (6.12) | 5 (2.38) | |
| PDS or IDS | .911 | ||
| PDS | 46 (46.93) | 100 (47.61) | |
| IDS | 52 (53.06) | 110 (52.38) | |
| Initial residual status, n (%) | .004 | ||
| R0 | 80 (81.63) | 140 (66.67) | |
| R1 | 8 (8.16) | 50 (23.80) | |
| R > 1 | 10 (10.20) | 20 (9.52) | |
| Initial CA125 level | 40.6–10,488 | 89–15,944 | .176 |
| Median = 1425.45 | Median = 1689.42 | ||
| Family history of breast and ovarian cancer, n (%) | .071 | ||
| 10 (10.20) | 10 (4.76) | ||
| Platinum-free internal duration, n (%) | .760 | ||
| <6 mo | 12 (12.24) | 20 (9.52) | |
| 6–12 mo | 40 (40.81) | 90 (42.85) | |
| >12 mo | 46 (46.93) | 100 (47.61) | |
| Objective response to most recent platinum-based regimen, n (%) | <.001 | ||
| Complete | 64 (65.30) | 100 (47.61) | |
| Partial | 32 (32.65) | 75 (35.71) | |
| Unknown | 2 (2.04) | 35 (16.67) | |
| Number of previous platinum-based chemotherapy regimens, n (%) | .007 | ||
| 1 | 66 (67.34) | 150 (71.42) | |
| 2 | 16 (16.32) | 10 (4.76) | |
| 3 | 4 (4.08) | 10 (4.76) | |
| 4 | 2 (2.04) | 15 (7.14) | |
| ≥5 | 10 (10.20) | 25 (10.20) | |
| Previous bevacizumab exposure, n (%) | .002 | ||
| 46 (46.93) | 60 (28.57) | ||
| BRCA-germline-mutation status, n (%) | <.001 | ||
| BRCA1 or 2 (+) | 48 (48.97) | 20 (9.52) | |
| BRCA1 or 2 (−), HRD (+) | 8 (8.16) | 20 (9.52) | |
| BRCA1 or 2 (−), HRD (−) | 42 (42.85) | 170 (80.95) | |
FIGO = international federation of gynecology and obstetrics.
Totally, 66 (67.34%) patients had only 1 chemotherapy regimen before Olaparib, while 32 patients underwent at least 2 regimens (32.65%), 16 (16.32%) of whom had undergone more than 3 previous regimens. There were 46 (46.93%) and 60 (28.57%) patients with previous bevacizumab treatment in 2 groups, respectively. In the With Olaparib group, the proportion of BRCA1 or 2 germline-mutation was 48.97%, and the rate in the Without Olaparib group was just 9.52%.
3.2. Treatment exposure
The median follow-up duration was 17.225 months (range, 2.0–36.2 months). The percentages of Olaparib users in the total patients at different time periods are shown in Table 2. And 86 patients used Olaparib for over 6 months (at the time of follow-up, 8 patients took Olaparib for <6 months and were in CR remission), 45 patients for over 12 months, and 6 patients over 24 months.
Table 2.
Outcomes of Olaparib maintenance in high-grade serous ovarian cancer patients outcomes.
| Observation period after Olaparib median (range), mo | 17.225 (2.0–36.2) |
| Olaparib maintenance period | |
| ≥6 mo | 86 (87.7) |
| ≥12 mo | 45 (45.91) |
| ≥24 mo | 6 (6.12) |
| Best overall response with Olaparib in patients with previous PR from most recent chemotherapy, n (%) | N = 78 |
| CR | 3 (3.84) |
| PR | 6 (7.69) |
| SD | 42 (53.84) |
| PD | 27 (34.6) |
| Type of dose modification due to AE, number of patients (%), n (%) | N = 98 |
| Dose reduction | 72 (73.40) |
| Drug discontinuation | 20 (20.40) |
| Both dose reduction and drug discontinuation | 8 (8.16) |
| Treatment applied other than dose reduction | 22 (22.44) |
| Recurrence event, n (%) | 22 (22.44) |
| Death event, n (%) | 8 (8.16) |
AE = adverse event, CR = complete remission, NE = not evaluable, PD = progression of disease, PR = partial remission, SD = stable disease.
3.3. Efficacy
As for best overall response to Olaparib maintenance in 78 patients with measurable or evaluable disease (partial remission, PR) from most recent chemotherapy, 3 (3.84%) patients had CR, 6 (7.69%) patients had PR, and 42 (53.84%) patients had stable disease (Table 2). Among the total of 98 patients, there were 22 (22.44%) recurrences and 8 (8.16%) deaths in the follow-up. Although the follow-up period was short, we derived Kaplan–Meier estimates of PFS and OS from the initiation of Olaparib maintenance therapy (Fig. 1). The median PFS from the initiation of Olaparib maintenance therapy was 17.0 months (95% CI, 3.357–30.643), with a 24-month PFS of 39.4% (Fig. 1). Since most patients enrolled received first-line platinum-based chemotherapy followed by Olaparib maintenance therapy, the OS was still unavailable at the end of this study.
Figure 1.
Kaplan–Meier estimates of PFS and OS of the patients. The median PFS was 17.0 mo, with a 24-mo PFS of 39.4%. The OS was still unavailable with a 24-mo OS of 85.5%. PFS = progression free survival.
3.4. Safety
Dose reduction and drug discontinuation accounted for 73.40% and 20.40%, respectively, in Olaparib patients, and there were 8 patients experienced both dose reduction and drug discontinuation. A total of 390 AEs (174 hematological AEs and 216 non-hematological AEs) were recorded (Table 3). The most common hematological AE was neutropenia (55.10%) including Grade one to Grade four levels, while fatigue (77.55%) was the most frequent non-hematological AE. In total, there were 40 episodes of G3 (Grade three) and Grade four hematological AEs, including 16.32% cases of anemia, 20.40% cases of neutropenia, and 4.08% cases of thrombocytopenia. Only 4.08% cases with G3 headache were observed. In total, dose reduction was performed 96 times, the proportion of dose reduction events was 64.7%, and the drug was interrupted for 96 times. There were 120 times of drug continuation without dose modification in which some AEs resolved spontaneously without management. Only 1 patient had drug interruption due to G3 neutropenia, and most neutropenia cases were of Grade one-Grade two without drug discontinuation. Although there was no event of drug discontinuation, 22.44% patients had their doses reduced due to fatigue, which was relieved with proper rest or diversion. In addition, since some patients were afraid of tumor recurrence, the decision of drug discontinuation should be made discreetly. The median time from therapy initiation to the onset of first AE was 1.9 months (range 0.2–2.8 months).
Table 3.
Adverse events (AEs).
| Total episodes, n (%) | Grade | Characterization of AEs | Management | |||||
|---|---|---|---|---|---|---|---|---|
| Grade 1–2, n (%) | Grade 3, n (%) | Grade 4, n (%) | Median time to onset of first event, mo, median (range) | Drug discontinuation, n (%) | Dose reduction, n (%) | Treatment applied with continuation (without dose reduction), n (%) | ||
| Any adverse event | 98 | |||||||
| Hematological | 174 | |||||||
| Anemia | 44 | 28 (28.57) | 16 (16.32) | 0 | 1.5 (0.2–2.0) | 0 | 14 (14.28) | 22 (22.44) |
| Neutropenia | 54 | 34 (34.69) | 12 (12.24) | 8 (8.16) | 1.6 (0.2–1.9) | 10 (10.20) | 16 (16.32) | 18 (18.36) |
| Thrombocytopenia | 50 | 46 (46.93) | 2 (2.04) | 2 (2.04) | 1.8 (0.4–2.2) | 8 (8.16) | 20 (20.40) | 8 (8.16) |
| Serum ALT/AST elevated | 26 | 26 (26.53) | 2.5 (1.5–2.8) | 2 (2.04) | 2 (2.04) | |||
| Non hematological | 216 | |||||||
| Nausea/vomiting | 46 | 46 (46.93) | 0.5 (0.2–1.2) | 6 (6.12) | 20 (20.40) | 4 (4.08) | ||
| Fatigue | 76 | 76 (77.55) | 0.8 (0.4–1.6) | 64 (65.30) | 22 (22.44) | 8 (8.16) | ||
| Oral mucositis | 24 | 24 (24.48) | 1.4 (0.8–2.0) | 4 (4.08) | 0 | 16 (16.32) | ||
| Peripheral | 24 | 24 (24.48) | 1.5 (1.0–1.7) | 2 (2.04) | 0 | 20 (20.40) | ||
| Neuropathy | 4 | 4 (4.08) | 0.8 | 0 | ||||
| Urticaria | 4 | 4 (4.08) | 1.2 | 2 (2.04) | 0 | |||
| Dizziness | 30 | 30 (30.61) | 0.8 (0.6–2.0) | 0 | 24 (24.48) | |||
| Headache | 4 | 4 (4.08) | 0.8 | 0 | 0 | |||
| Soft tissue infection | 4 | 4 (4.08) | 2.4 (2.2–2.6) | 0 | 0 | |||
3.5. Quality of life
Table 4 shows the QoL scores of patients with different Olaparib strata. At the early stage of the enrollment survey, the overall health score of QLQ-C30 was very low. The lowest scores were found in social functioning and cognitive functioning. The QLQ-OV28 sexual score was the lowest (Table 4). Our results showed that patients without Olaparib scored lower in physical function (P = .038), role functioning (P = .010), cognitive functioning (P = .005), emotional functioning (P = .006), and social functioning (P < .0001). They suffered more severe symptoms such as constipation (P = .001), poor body image (P = .003), poor attitude toward treatment and disease (P < .0001), and other chemotherapy side effects (P = .020). Then, we identified patients with deteriorating QoL who had lower scores in the functional domain, global health, and sexual function or worsened conditions in other symptom domains during follow-up (Table 4). We applied a logistic regression model to determine whether Olaparib status could predict the risk of QoL deterioration. The results showed that patients without Olaparib had a significantly higher risk of deterioration in QoL in physical functioning (P = .001), role functioning (P = .0140), emotional functioning (P = .021), pain (P = .010), and financial difficulties (P = .003).
Table 4.
Univariate and multivariate analysis of patients’ Quality of Life in Olaparib group vs without Olaparib group.
| Overall | Olaparib group | Without Olaparib group | Coefficient (95%CI) (Univariate) | P | Coefficient (95%CI) (Multivariate) | P | |
|---|---|---|---|---|---|---|---|
| n | 272 | 80 | 192 | ||||
| C30 | |||||||
| Physical functioning (mean [SD]) | 89.55 (8.55) | 96.00 (5.47) | 84.17 (6.76) | −0.27 (−0.44 to −0.14) | <.001 | −0.28 (−0.48 to −0.14) | <.001 |
| Role functioning (mean [SD]) | 87.12 (16.81) | 96.67 (10.26) | 79.17 (17.20) | −0.1 (−0.18 to −0.04) | .003 | −0.09 (−0.17 to −0.03) | .008 |
| Emotional functioning (mean [SD]) | 64.39 (21.91) | 81.11 (9.61) | 50.46 (19.38) | −0.15 (−0.26 to −0.08) | <.001 | −0.16 (−0.3 to −0.08) | .004 |
| Cognitive functioning (mean [SD]) | 82.20 (13.16) | 88.33 (12.21) | 77.08 (11.85) | −0.08 (−0.14 to −0.03) | .008 | −0.15 (−0.26 to −0.07) | .003 |
| Social functioning (mean [SD]) | 81.82 (17.91) | 92.50 (12.65) | 72.92 (16.89) | −0.08 (−0.13 to −0.04) | <.001 | −0.07 (−0.12 to −0.02) | .006 |
| Fatigue (mean [SD]) | 14.14 (15.60) | 8.33 (13.43) | 18.98 (15.88) | 0.05 (0.01–0.1) | .03 | 0.04 (0–0.1) | .091 |
| Nausea and vomiting (mean [SD]) | 10.23 (15.76) | 4.17 (9.17) | 15.28 (18.33) | 0.06 (0.01–0.13) | .032 | 0.08 (0.01–0.16) | .038 |
| Pain (mean [SD]) | 11.74 (16.31) | 6.67 (13.68) | 15.97 (17.36) | 0.04 (0–0.09) | .071 | 0.06 (0–0.12) | .07 |
| Dyspnea (mean [SD]) | 11.36 (18.94) | 1.67 (7.45) | 19.44 (21.80) | 0.08 (0.03–0.17) | .011 | 0.13 (0.05–0.24) | .005 |
| Insomnia (mean [SD]) | 25.00 (21.72) | 16.67 (20.23) | 31.94 (20.80) | 0.04 (0.01–0.07) | .025 | 0.05 (0.01–0.1) | .019 |
| Appetite loss (mean [SD]) | 18.18 (20.90) | 10.00 (19.04) | 25.00 (20.26) | 0.04 (0.01–0.08) | .022 | 0.03 (0–0.07) | .084 |
| Constipation (mean [SD]) | 21.97 (24.84) | 15.00 (25.31) | 27.78 (23.40) | 0.02 (0–0.05) | .094 | 0.01 (−0.02 to 0.04) | .437 |
| Diarhoea (mean [SD]) | 5.30 (12.33) | 1.67 (7.45) | 8.33 (14.74) | 0.06 (0–0.15) | .102 | 0.14 (0.05–0.26) | .006 |
| Financial difficulties (mean [SD]) | 32.58 (28.29) | 31.67 (29.57) | 33.33 (27.80) | 0 (-0.02–0.02) | .844 | 0.01 (−0.01 to 0.04) | .315 |
| OV28 | |||||||
| Abdominal GI (mean [SD]) | 21.59 (20.09) | 3.61 (7.27) | 36.57 (13.99) | 0.16 (0.09–0.26) | <.001 | 0.15 (0.08–0.27) | <.001 |
| Peritheral neuropathy (mean [SD]) | 23.11 (18.40) | 10.83 (13.55) | 33.33 (15.54) | 0.12 (0.06–0.2) | .001 | 0.11 (0.04–0.2) | .007 |
| Hormanal (mean [SD]) | 21.97 (21.80) | 7.50 (10.08) | 34.03 (21.69) | 0.14 (0.06–0.25) | .002 | 0.15 (0.06–0.28) | .006 |
| Body image (mean [SD]) | 27.65 (24.10) | 10.00 (15.67) | 42.36 (19.65) | 0.1 (0.06–0.17) | <.001 | 0.11 (0.05–0.19) | .001 |
| Attitude to disease treatment (mean [SD]) | 32.32 (21.68) | 18.89 (22.25) | 43.52 (13.48) | 0.07 (0.03–0.13) | .001 | 0.07 (0.03–0.13) | .003 |
| Chemotherapy side effects (mean [SD]) | 24.70 (18.33) | 8.33 (8.89) | 38.33 (11.67) | 0.22 (0.12–0.39) | <.001 | 0.23 (0.11–0.43) | .003 |
| Other single items (mean [SD]) | 13.64 (15.69) | 4.44 (6.65) | 21.30 (17.00) | 0.13 (0.06–0.22) | .002 | 0.14 (0.05–0.25) | .006 |
| Sexuality see blow (mean [SD]) | 9.09 (19.17) | 0.83 (3.73) | 15.97 (23.81) | 0.09 (0.02–0.26) | .082 | 0.08 (0.02–0.24) | .105 |
SD = stable disease.
4. Discussion
In addition to surgery and chemotherapy, PARPi are more likely to be used as first-line maintenance therapy or chemotherapy to achieve CR/PR maintenance after recurrence. In this study, 66 patients received first-line maintenance therapy and 32 second-line maintenance therapy. The patients with BRCA 1/2 mutations accounted for 48.97%, which was slightly different for Study 19 (BRCA1 account for 65%; BRCA2 account for 35%; BRCA1 and 2 account for 2%) and SOLO-1 (BRCA1 73%; BRCA2 25%). Patients’ median age in SOLO-1was basically consistent with that in our study.[9] In addition, our study only enrolled epithelial serous ovarian cancer patients, while both Study 19 and SOLO-1 encompassed cases with fallopian tube carcinoma and primary peritoneal carcinoma. Importantly, almost no Asian and Chinese patients were included in Study 19 or SOLO-1, and the patients in our study were all Chinese. Hence, our data are more reliable in guiding the clinical practice of Chinese gynecological oncologists and may enrich the global data of Olaparib.
Since Olaparib has only been approved in China for a short period of time, our median PFS is 17.0 months. Olaparib and other PARPi maintenance treatment can significantly improve the overall PFS of platinum-sensitive relapsed ovarian cancer patients according to the registered clinical trials. The results of Study 19 indicated that patients receiving Olaparib 400mg twice a day as maintenance therapy had a longer PFS (8.4 vs 4.8 months, HR 0.35, P < .001) with a greater benefit in BRCA (germline and somatic) mutated subgroup (11.2 vs 4.3 months, HR 0.18, P < .0001).[4,7,10] Following Study 19, as all registered trials, Olaparib was administered to very selected patients from highly experienced providers with very strict rules, timelines and schedules per protocol. This improved PFS obtained in an ideal setting needs external validity in a less selected population. The results of the highly anticipated 5-year follow-up of the SOLO1 study showed a median PFS of up to 56 months, a reduced risk of disease progression or death by 67%, and 48% of patients with no disease progression in 5 years. Yet the real-world studies are needed to define if drugs are effective in the authentic clinical setting. Few results from the real-world use of Olaparib have been reported, either with a short follow up[11] or a small population,[12] lacking essential clinical information like BRCA status[13] and focusing above all on safety.
The results of weekly blood routine examination were regularly collected, multiple telephone follow-up and questionnaire surveys were conducted, and the adverse reactions of patients were recorded in detail. In our study, the most common hematological AE was neutropenia, while non hematological AE was fatigue. In Study 19, the most common non-hematologic AE was nausea (73%), and the most frequent hematologic AE was anemia (26%). In SOLO-1, the most common non-hematologic and hematologic AEs were diarrhea (3.1%) and anemia (21.5%), respectively. In our study, the most common hematological AE was neutropenia, while non hematological AE was fatigue. The main reason for the difference is that the patients in our study had weekly blood counts during the medication, and thus more neutropenia events were observed. And the difference in AEs can also be attributed to the different races. Besides, the doses of oral drugs in our study were mainly set based on the previous studies among foreign populations. The appropriate dose for Chinese patients needs further research. In both Study 19 and SOLO-1, treatment was discontinued for any Grade 3 or 4 AEs and then restarted if toxicity was resolved or decreased to Grade 1.[14] In Study 19, 36% of patients experienced dose interruption.
Olaparib treatment was approved in China based on the National Comprehensive Cancer Network guideline and is mandatory for gynecologic oncologists in China to follow the recommendations and guidelines of National Comprehensive Cancer Network. The number of ovarian cancer survivors is increasing, making survivorship issues such as QoL an important component of their care. There are several articles reporting the effectiveness and safety of Olaparib in patients with high-grade serous ovarian cancer,[14,15] but the reports on QoL in patients with Olaparib are few, especially rare of the QoL issues in high-grade serous ovarian cancer patients with Olaparib maintenance therapy of Chinese patients. Our results are comparable to those of Study 19, but we used different indications and regimen (tablets 300 mg, bid). In the current study, contrary to what we expected, we confirm the differences between taking Olaparib and Without Olaparib group in the aspect of QoL outcomes, showing that without Olaparib is associated with multiple poorer QoL outcomes of ovarian cancer survivors including physical, emotional, cognitive and social functioning. Furthermore, we found that without Olaparib women report more symptomatology, including constipation, poor body image and poor attitude toward treatment. In addition, compared to their Without Olaparib counterparts, physical and role functioning were rated better by taking Olaparib survivors and they reported a higher global health status and less symptoms. The reasons for our analysis may be: The adverse reactions caused by Olaparib are relatively mild, mostly for Grade 1 and 2, which have a relatively gentle impact on the QoL. Patients taking Olaparib psychologically feel that their diseases can be treated, and their mental state is obviously better than that of patients without Olaparib, so they have a high level in emotion and cognition. Some patients taking Olaparib devote themselves to work, and more communication with the outside world can increase their yearning for and awareness of a better life. Although many studies have investigated QoL in cancer survivors, we were—to the best of our knowledge—the first to compare the QoL of taking Olaparib and without Olaparib ovarian cancer survivors with a center of population. Future efforts should focus on developing lifestyle interventions to improve the outcomes of this patient group.
This study has several limitations. First of all, because this study is based on ovarian cancer patients undergoing oral Olaparib maintenance treatment in our center, and the detection time is close to the follow-up end point, there is obvious survivor bias. Therefore, the OS analyzed in this study is relatively short. Secondly, the sample size of this study is small, and it is only a preliminary exploratory study. In the subsequent studies, we will expand the sample size and increase the OS statistics. The conclusions obtained in this study and their specific mechanisms need further confirmation. A prospective multicenter study is warranted for a more in-depth analysis of the ideal strategy of approach, and to determine the criteria to offer expectant PARPi management in patients with ovarian cancer.
Author contributions
Conceptualization: Yi Jiang, Lin Zhang, Wenjun Cheng.
Data curation: Ting Xu, Lin Yuan, Shan Wu.
Formal analysis: Lin Yuan, Xinjia Ruan.
Funding acquisition: Wenjun Cheng.
Investigation: Ting Xu, Shan Wu.
Methodology: Yi Jiang, Lin Zhang, Xinjia Ruan.
Project administration: Wenjun Cheng.
Resources: Yi Jiang.
Software: Yi Jiang, Xinjia Ruan, Huangyang Meng.
Supervision: Lin Yuan, Wenjun Cheng.
Validation: Shan Wu.
Visualization: Xinjia Ruan, Huangyang Meng.
Writing – original draft: Yi Jiang, Ting Xu.
Writing – review & editing: Lin Yuan, Lin Zhang, Xinjia Ruan, Huangyang Meng, Wenjun Cheng.
Abbreviations:
- AEs
- adverse events
- CR
- complete response
- G3
- Grade three
- PARPi
- poly ADP-ribose polymerase inhibitor
- PFS
- progression free survival
- PR
- partial response
- QLQ-OV28
- Quality of Life Ovarian Cancer 28 Questionnaire
- QoL
- quality of life
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the First affiliated Hospital of Nanjing Medical University (No. 2021-SR-270).
This study was funded by Experimental and Clinical Study of Novel Treatment of Ovarian Cancer, The Project of Jiangsu Provincial Medical Innovation Team (CXTDA2017008).
The authors have no conflicts of interest to disclose.
JY and XT contributed equally to this work.
How to cite this article: Jiang Y, Xu T, Yuan L, Zhang L, Ruan X, Wu S, Meng H, Cheng W. Analysis of adverse events and quality of life in high-grade serous ovarian cancer patients with Olaparib maintenance therapy: A single-center study in China. Medicine 2023;102:15(e33434).
Contributor Information
Yi Jiang, Email: jiangyi@jsph.org.cn.
Ting Xu, Email: tingxu_doc@qq.com.
Lin Yuan, Email: feilin1915@163.com.
Lin Zhang, Email: feilin1915@163.com.
Xinjia Ruan, Email: ruan.cpu@foxmail.com.
Shan Wu, Email: 1562931703@qq.com.
Huangyang Meng, Email: 1289189947@qq.com.
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