Real-World Study Highlights PARP Inhibitor Challenges in Ovarian Cancer Care

Nearly half of the patients with advanced ovarian cancer receiving first-line poly-ADP-ribose polymerase (PARP) inhibitor maintenance treatment in this real-world study relapsed, emphasizing the need for refined postrecurrence treatment strategies.¹

The authors of the ESMO Open study emphasized that recent randomized controlled trials of PARP inhibitor use in the first-line maintenance setting among patients with advanced ovarian cancer showed significant improvements in progression-free survival (PFS). However, relapse is still a major problem, with the 3-year PFS ranging from 12% to 60% in these trials.

Despite this, PARP inhibitors are widely used in clinical practice. Findings from a large real-world study suggested that up to 79% of patients with primary advanced ovarian cancer may be eligible for PARP maintenance treatment under European reimbursement policies.²

This has expanded the patient population, creating new challenges for oncologists, especially in understanding the impact of PARP inhibitors on recurrence and postrecurrence survival outcomes.¹ These factors could influence treatment decisions, including local treatments such as secondary cytoreductive surgery (SCS) and stereotactic radiotherapy (SBRT).

There is limited literature on the outcomes of using first-line PARP inhibitors outside clinical trial settings. Therefore, the researchers aimed to provide data on disease presentation, recurrence rates, and treatment modalities at progression in patients treated with first-line PARP inhibitors at a tertiary referral center for ovarian cancer care.

Nearly half of patients with advanced ovarian cancer treated with first-line PARP inhibitors experienced recurrence in this real-world study, emphasizing the need for enhanced strategies to optimize postrecurrence treatment. | Image Credit: Queenmoonlite Studio - stock.adobe.com

To do so, they evaluated real-world data from patients with ovarian cancer who received first-line PARP inhibitor maintenance treatment at the gynecologic oncology unit of the Fondazione Policlinico Universitario A. Gemelli in Rome, Italy, from January 2019 to December 2022. All patients had a clinical complete or partial response after 6 cycles of platinum-based chemotherapy.

The researchers collected clinicopathological data, tissue samples, and/or germline BRCA and homologous recombination deficiency status. During maintenance, patients were evaluated with CT scans, physical examinations, and cancer antigen 125 (CA 125) serum level measurements every 6 months for 2 to 3 years.

Platinum sensitivity was defined as recurrence occurring 6 or more months after completing primary platinum-based chemotherapy. Based on the number of nodules, recurrence sites were classified as discrete/oligometastatic (≤ 5 nodules) or diffuse (> 5 nodules). Treatment options for platinum-sensitive recurrence included second-line chemotherapy and local treatments, with the option to continue maintenance therapy or start second-line chemotherapy.

For survival analysis, the researchers included patients who experienced progression or death after recurrence diagnosis, as well as those who had at least 12 months of observation without an event. PFS was defined as the time between the last administration of first-line chemotherapy and the date of disease recurrence, progression, last follow-up, or death, whichever occurred first. The researchers used the Chi-square test and Cox regression model to assess survival outcomes and prognostic factors, respectively.

The researchers identified 373 eligible patients, 51.5% of whom carried a somatic or germline BRCA mutation. Neoadjuvant chemotherapy was administered in 46.9% of cases, and 89.5% achieved complete cytoreduction.

As of April 2024, 167 patients (44.8%) experienced a recurrence, with a median follow-up of 38 months (95% CI, 36.1-39.9). Of these patients, 69 (18.5%) died of disease. Most patients recurred during maintenance (n = 155; 92.8%). Overall, the PFS was less than 6 months in 36 patients (9.7%), between 6 and 12 months in 53 patients (14.2%), and 12 months or greater in 78 patients (20.9%).

Of the 167 patients with disease recurrence, 44.9% had less than 5 lesions, while 55.1% had 5 or more nodules or peritoneal carcinomatosis. Recurrences in patients with BRCA mutations were more likely to present as oligometastatic (64.5%; P < .001). Therefore, patients with BRCA mutations were more than 3 times as likely to develop oligometastatic disease (HR, 3.014; 95% CI, 1.486-6.113; P = .002).

Among the 131 platinum-sensitive patients, only 3 (2.2%) did not undergo further treatment. Of the remaining patients, 74 (56.6%) received second-line chemotherapy, while 54 (41.2%) received local treatment (28, SCS; 18, SBRT).

Overall, PARP inhibitors were continued in 53.7% of patients who received local treatment for oligometastatic disease. After local treatment, patients in the SCS group received either second-line chemotherapy (61.3%) or prolonged PARP inhibitor therapy (38.7%). The median duration of extended PARP inhibitor administration was about 7 months (95% CI, 3.7-10.3). More specifically, it was 8 months (95% CI, 4.4-11.6) for the SBRT group and 7 months (95% CI, 3.0-11.1) for the SCS group.

Lastly, the median PFS among the total population was 39 months (95% CI, 27.5-50.5). The researchers found that patients with an oligometastatic recurrence pattern experienced later recurrences (median PFS, 13 months; 95% CI, 10.2-15.8; P = .004) than the diffuse recurrence group (median PFS, 9 months; 95% CI, 7.3-10.7; P = .004).

They researchers acknowledged their study’s limitations, including its retrospective nature and small sample size, which may have led to selection biases and reduced statistical power. Despite these limitations, the researchers expressed confidence in their findings.

“Our study demonstrates that data from randomized trials on PARP inhibitor maintenance in the first-line setting are applicable to the real-world setting in a similar fashion,” the authors concluded. “The analysis of these data aims not to replace the results of a randomized trial but to provide a different perspective, unrestricted by stringent inclusion criteria, offering clinicians practical prognostic insights applicable to the daily clinical setting.”

References

1. Loverro M, Marchetti C, Salutari V, et al. Real-world outcomes of PARP inhibitor maintenance in advanced ovarian cancer: a focus on disease patterns and treatment modalities at recurrence. ESMO Open. Published online January 17, 2025. doi:10.1016/j.esmoop.2024.104119

2. Marth C, Abreu MH, Andersen KK, et al. Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial). Cancer. 2022;128(16):3080-3089. doi:10.1002/cncr.34350