FormalPara Key Summary Points

Why carry out this study?

Patients diagnosed with ovarian cancer (OC) treated with first-line (1L) platinum-based chemotherapy with or without bevacizumab often receive first-line maintenance (1LM) therapy.

Understanding patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab in a real-world setting remains an unmet need.

What did the study ask?

What is the time to treatment discontinuation (TTD) and time to next treatment (TTNT) for patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab in a real-world setting?

What was learned from the study?

These real-world findings provide valuable insights on the use of niraparib monotherapy as 1LM, regardless of bevacizumab use with 1L chemotherapy.

Switch 1LM niraparib monotherapy may be a viable treatment option for patients with advanced OC.

Introduction

In the USA, there were an estimated 19,710 new cases of and 13,270 deaths from ovarian cancer (OC) in 2023 [1]. Patients who develop OC often experience nonspecific symptoms, and there is no screening for early detection of OC, resulting in approximately 75% of cases being diagnosed at an advanced stage [2]. Thus, the overall prognosis remains poor, with an estimated 5-year survival rate of 31% [3].

For patients diagnosed with OC, standard first-line (1L) treatment involves a combination of surgical intervention and platinum-based chemotherapy with or without bevacizumab [4, 5]. Following 1L treatment, maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor is recommended in patients who have achieved complete or partial response to chemotherapy to prolong survival and delay disease recurrence or progression [6].

In the PRIMA trial, among patients with advanced OC with a complete or partial response to 1L platinum-based chemotherapy, the PARP inhibitor niraparib demonstrated a significantly improved progression-free survival (PFS) of 13.8 months versus 8.2 months for placebo (hazard ratio, 0.62; 95% CI 0.50–0.76; p < 0.001) [7]. Following these results, niraparib monotherapy was approved for first-line maintenance (1LM) treatment of adult patients with advanced OC with a complete or partial response to 1L platinum-based chemotherapy [8, 9]. In the real-world CHAR1ZMA study, among 414 patients with epithelial OC treated with platinum-based chemotherapy in the 1L setting, followed by 1LM niraparib monotherapy, the median time to next treatment (TTNT), a proxy for real-world PFS, was 13.3 months (95% CI 12.0–15.8 months) [10]. However, limited data exist on real-world outcomes among patients with OC who receive switch maintenance therapy with 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab.

The objective of this retrospective observational study was to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab in a real-world setting.

Methods

Data Source

This study was conducted using data from the Flatiron Health US-based nationwide database of deidentified electronic health record (EHR)-derived data from approximately 280 cancer clinics representing an estimated 800 sites of care [11, 12]. The database contains patient-level structured and unstructured data, curated via technology-enabled abstraction from physician notes and other unstructured documents. For this study, data were custom curated to capture all patients treated with niraparib from the overall OC population available in the database, using the data cutoff of 30 November 2022. The deidentified data were subject to obligations to prevent reidentification and protect patient confidentiality.

Study Population

Patients diagnosed with OC during the study period (1 January 2011 to 30 November 2022) were eligible if they received 1L combination chemotherapy plus bevacizumab followed by 1LM niraparib monotherapy. Initiation of 1LM niraparib monotherapy must have occurred between 1 January 2017 and 2 September 2022. Patients were required to be at least 18 years of age at initial OC diagnosis, have evidence of epithelial histology (serous, clear cell, mucinous, endometrioid, transitional cell, epithelial not otherwise specified, or unknown), and have at least 1 day of follow-up after the index date (defined as the date of initiation of 1LM niraparib monotherapy). Patients were excluded if they were likely to have a misclassified line of therapy, defined as having a record of receiving 1L or second-line (2L) PARP inhibitor monotherapy. Lines of therapy were defined with a prespecified database-specific, rules-based, oncologist-defined line-of-therapy algorithm. Patients were followed from index date until the first occurrence of death, end of follow-up, or end of study (30 November 2022).

Study Outcomes

Patient demographics and clinical characteristics were collected from the index date or within the baseline period, defined as the time between initial OC diagnosis and index date. Specifically, age, geographic region, race, ethnicity, and practice type were collected. Clinical characteristics included year of initial OC diagnosis, year of end of 1L therapy, duration of 1L therapy, prior primary or interval cytoreductive surgery, residual disease status, height, weight, blood pressure, hypertension, platelet count, biomarker status, Eastern Cooperative Oncology Group performance status score, histology at OC diagnosis, and stage at initial diagnosis. Dosing characteristics for 1LM niraparib monotherapy included starting daily dose, occurrence and type of dose modifications, occurrence of dose discontinuation, and reason(s) for discontinuation.

Individualized starting dose (ISD) was determined based on the patient’s weight and platelet count (closest to index date, from 28 days prior to the last date of 1L induction treatment up to index date). Patients weighing < 77 kg or with a platelet count of < 150,000/µL were indicated for a 200-mg starting dose. Patients weighing ≥ 77 kg and with platelet count ≥ 150,000/µL were indicated for a 300-mg starting dose. Starting dose status was a categorical variable defined as ISD (a patient started at the dose indicated by ISD calculation), received a dose lower than ISD (e.g., indicated for 300 mg but had a starting dose of 200 mg or 100 mg), or received a dose higher than ISD (e.g., indicated for 200 mg but had a starting dose of 300 mg); patients with missing data for any of these variables had their starting dose status classified as “other or unknown.”

Real-world clinical outcomes of interest included time to treatment discontinuation (TTD) of niraparib and TTNT. TTD was measured as the time from start of 1LM niraparib monotherapy to the date of 1LM niraparib monotherapy discontinuation; patients who did not discontinue their maintenance therapy were censored at the last drug episode. TTNT, a proxy for real-world PFS, was measured from the end date of 1L therapy until the earliest of 2L initiation or death; patients who did not initiate subsequent treatment or die were censored at the last clinical activity or end of the study period.

Statistical Methods

Patient baseline characteristics were summarized descriptively for the overall study population. Kaplan–Meier curves were used to describe median TTD and TTNT (in months) and associated 95% CIs.

Ethical Approval

This study complied with all applicable patient privacy laws. The deidentified data were subject to obligations to prevent reidentification and protect patient confidentiality. There was no direct patient contact or primary collection of individual human participant data. Study results and analyses omit patient identification. Therefore, informed consent and ethics committee or institutional review board approval were not required. The data that support the findings of this study have been originated by Flatiron Health, Inc, and we have permission to use the data.

Results

Of 11,094 patients diagnosed with OC during the study period, 93 patients met all eligibility criteria and were included in this analysis (Fig. 1). The median age at index was 67 years (IQR 60–72 years; Table 1). A majority of patients were white (56/93, 60.2%) and were treated in a community-based oncology practice (87/93, 93.5%). Most patients had stage III (50/93, 53.8%) or IV (33/93, 35.5%) disease at diagnosis. All patients received 1L platinum-based chemotherapy plus bevacizumab. Most patients had BRCA wild-type/homologous recombination–proficient (HRp) or BRCA wild-type/HR unknown disease (70/93, 75.3%). A total of 18 patients (19.4%) had homologous-recombination-deficient (HRd) disease (n = 8 with BRCA-mutated disease and n = 10 with BRCA wild-type disease). The remaining 5.4% (5/93) of patients had unknown test results for both BRCA and homologous-recombination-deficiency (HRD) status. Median time from end of 1L therapy to 1LM initiation was 35.0 days (IQR 25.0–53.9 days).

Fig. 1
figure 1

Study population attrition. 1L first-line, 1LM first-line maintenance, 2L second-line, NOS not otherwise specified, OC ovarian cancer, PARPi poly(ADP-ribose) polymerase inhibitor

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Table 1 Patient demographics and clinical characteristicsa
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Most patients initiated 1LM niraparib monotherapy at the ISD (57.0%), which was most commonly 200 mg (53.8%; Table 2). At the end of the study period, 65.6% of patients discontinued niraparib, most commonly because of disease progression (62.3%) and/or toxicity (44.3%).

Table 2 Niraparib dosing characteristicsa
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Median follow-up time was 16.3 months (IQR 8.7–25.4 months). The observed median TTD of 1LM niraparib monotherapy was 9.3 months (95% CI 6.1–11.3 months; Fig. 2). The observed median TTNT of 1LM niraparib monotherapy was 12.9 months (95% CI 11.5–19.0 months, Fig. 3).

Fig. 2
figure 2

Real-world TTD. TTD was measured from the first dose of 1LM niraparib monotherapy to the date of discontinuation of niraparib monotherapy; patients who did not discontinue their maintenance therapy were censored at the last drug episode. 1LM first-line maintenance, CI confidence interval, TTD time to treatment discontinuation

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Fig. 3
figure 3

Real-world TTNT. TTNT was measured from the end date of 1L therapy until the earliest of initiation of 2L or death; patients who did not initiate subsequent treatment or die were censored at the last clinical activity or the end of the study period. 1L first-line, 1LM first-line maintenance, 2L second-line, CI confidence interval, TTNT time to next treatment

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Discussion

In this real-world observational study, patients with OC who received switch 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab had a median TTD of 9.3 months and a median TTNT, a proxy for real-world PFS, of 12.9 months. The TTNT reported here was consistent with the real-world CHAR1ZMA study [10], in which the median TTNT from the end of 1L treatment was 13.3 months (95% CI 12.0–15.8 months) for patients receiving 1LM niraparib monotherapy following 1L platinum-based chemotherapy with or without bevacizumab [10]. Taken together, these results support real-world use of niraparib monotherapy as 1LM, regardless of bevacizumab use with 1L chemotherapy.

Results should be considered within the context of existing, related clinical trial data. However, trial comparisons should not be interpreted as conclusive because of differences in the number of patients included, study treatments/designs, and the way study outcomes were measured/defined. In this study, the median TTNT of 12.9 months was similar to the median PFS of 13.8 months reported for patients receiving 1LM niraparib following 1L platinum-based chemotherapy in the PRIMA trial [7, 13]. In the GOG-0218 study, conducted prior to PARP inhibitor approvals, the addition of bevacizumab to 1L chemotherapy with or without bevacizumab maintenance for up to 15 months was investigated [14]. With a median overall follow-up of 17.4 months, the median PFS was 14.1 months for patients who received 1L chemotherapy plus bevacizumab, with bevacizumab maintenance; 11.2 months for those who received bevacizumab in the 1L induction phase only; and 10.3 months for patients who did not receive bevacizumab in either the 1L or the 1LM setting [14]. Importantly, although median PFS values in GOG-0218 were similar to the median TTNT value reported here, PFS was measured from the start of 1L therapy, whereas TTNT was measured from the start of 1LM. In the PAOLA-1 study, following 1L platinum-based chemotherapy plus bevacizumab and with a median follow-up of 22.9 months, patients who received 1LM combination olaparib plus bevacizumab had a median PFS of 22.1 months, which was significantly greater than the median PFS of 16.6 months for patients who received continuation of 1LM with bevacizumab alone [15]. However, those PFS values were for the overall population, regardless of biomarker status, unlike this study, where patients had mostly BRCA wild-type/HRp or BRCA wild-type/HR unknown disease. In the PAOLA-1 study, when restricting to the 419 patients who had HRp/HR unknown tumors, the median PFS was 16.9 months in the olaparib plus bevacizumab group, which was not significantly different from the median PFS of 16.0 months in the placebo group [15].

The findings presented here should be considered within the context of certain limitations, including some that are inherent to studies that use EHR-derived databases. Specifically, data are collected for the purposes of clinical management of oncology patients and not for clinical research purposes. There may be limitations in abstraction rules used in the database, but these rules were considered in the design of this study. Additionally, the algorithms defining lines of therapy may undergo updates as the treatment landscape evolves, thereby restricting their ability to accurately represent OC treatment in the real-world setting. This study used a real-world, EHR-derived database, which represents US patients with cancer cared for in community-based practices, but it may not fully represent the overall advanced or recurrent OC population, those who receive care in academic-based practices, or global populations. There were 93 patients who met inclusion criteria and were included in this analysis. The small sample size may be reflective of limited real-world utilization of switch maintenance. Patients who receive bevacizumab in the 1L induction phase may be more likely to receive bevacizumab as 1LM. Despite this small sample size, these results still contribute to the understanding of this patient population and add important real-world insights into switch 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab. Finally, while TTNT serves as a proxy for real-world PFS, the measure may be influenced by patients initiating next treatment because of toxicity and not survival.

Conclusion

In summary, this real-world descriptive analysis offers valuable insights into switch 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab in patients with OC. These results suggest that switch 1LM niraparib monotherapy may be a viable treatment option for patients with advanced OC.