scholarly journals Population-adjusted indirect treatment comparison of maintenance PARP inhibitor with or without bevacizumab versus bevacizumab alone in women with newly diagnosed advanced ovarian cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110496
Author(s):  
Robert Hettle ◽  
Charles McCrea ◽  
Chee Khoon Lee ◽  
Richard Davidson
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Treatment ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Newly Diagnosed ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Unselected Population ◽  
Indirect Treatment ◽  
Positive Population

Background: In patients with newly diagnosed ovarian cancer, bevacizumab and poly(ADP-ribose) polymerase (PARP) inhibitors, alone or in combination, have shown benefit as maintenance treatment following platinum-based chemotherapy. However, no trials have compared a PARP inhibitor plus bevacizumab versus a PARP inhibitor, or a PARP inhibitor versus bevacizumab. We performed an unanchored population-adjusted indirect treatment comparison to estimate the relative efficacy and safety of maintenance treatments for newly diagnosed advanced ovarian cancer. Methods: Analyses were performed using aggregate data from the PRIMA trial and patient-level data from a subset of patients from the PAOLA-1 trial that met surgery and staging eligibility criteria of PRIMA. Propensity weights were used to match baseline characteristics of the PAOLA-1 subset to those of the PRIMA population. Analysis was performed in overall (biomarker-unselected) and homologous recombination repair deficiency (HRD)-positive populations. Results: A total of 595/806 (266/387 HRD-positive) PAOLA-1 patients were included. After matching, the effective sample size for PAOLA-1 was 532 (242 HRD-positive). Maintenance olaparib plus bevacizumab reduced the risk of disease progression or death by 43% [hazard ratio (HR) 0.57; 95% confidence interval (CI): 0.47–0.69] versus niraparib and by 40% (HR 0.60; 95% CI: 0.49–0.74) versus bevacizumab in the biomarker-unselected population and by 43% (HR 0.57; 95% CI: 0.41–0.79) and 60% (HR 0.40; 95% CI: 0.29–0.55), respectively, in the HRD-positive population. Progression-free survival (PFS) benefits of maintenance niraparib and bevacizumab arms were comparable in the biomarker-unselected population (HR 1.07; 95% CI: 0.87–1.32); however, niraparib showed a 30% reduced risk compared with bevacizumab (HR 0.70; 95% CI: 0.51–0.97) in the HRD-positive population. Conclusions: In biomarker-unselected and HRD-positive patients, combination treatment with olaparib plus bevacizumab as maintenance treatment improves PFS for women with newly diagnosed advanced ovarian cancer compared with either bevacizumab or niraparib alone. Results are hypothesis generating and could guide randomised trial design.

scholarly journals Maintenance Treatment of Newly Diagnosed Advanced Ovarian Cancer: Time for a Paradigm Shift?

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5756
Author(s):  
Paul DiSilvestro ◽  
Nicoletta Colombo ◽  
Philipp Harter ◽  
Antonio González-Martín ◽  
Isabelle Ray-Coquard ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Practice ◽  
Maintenance Treatment ◽  
Parp Inhibitor ◽  
Brca2 Mutation ◽  
Advanced Ovarian Cancer ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
Future Research ◽  
Newly Diagnosed

Recent data have demonstrated substantial efficacy with poly (ADP-ribose) polymerase (PARP) inhibitors as treatment and/or maintenance therapy in patients with newly diagnosed advanced epithelial ovarian cancer (EOC). Here, we review efficacy and safety results from four recent Phase III trials in newly diagnosed EOC: SOLO1 (olaparib), PAOLA-1 (olaparib in combination with bevacizumab), PRIMA (niraparib), and VELIA (veliparib). The implications of these data for current clinical practice and areas for future research are discussed, including ongoing studies of targeted agents in the newly diagnosed setting. Data from SOLO1, PAOLA-1, PRIMA, and VELIA confirm the benefit of PARP inhibitors (olaparib, niraparib, veliparib) for women with newly diagnosed EOC. The greatest benefit was seen in patients with a BRCA1 and/or BRCA2 mutation or in the homologous recombination deficiency (HRD)-test positive subgroup. These four well-conducted studies have generated practice-changing data. However, deciding how to apply these results in clinical practice is challenging, and substantial differences in trial design impede cross-trial comparisons. Recent PARP inhibitor approvals (olaparib, niraparib) in the newly diagnosed EOC setting have provided new maintenance treatment options for a broader patient population. The results of these studies call for personalized medicine based on biomarker profile and other factors, including tolerability, cost considerations, and physician and patient preference. Important areas for future research include appropriate use of both BRCA mutation and HRD testing to inform magnitude of PARP inhibitor benefit as well as exploring further options for patients who are HRD-test negative and for those who become PARP inhibitor resistant.

DUO-O: A randomized phase III trial of durvalumab (durva) in combination with chemotherapy and bevacizumab (bev), followed by maintenance durva, bev and olaparib (olap), in newly diagnosed advanced ovarian cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5598-TPS5598 ◽  
Author(s):  
Philipp Harter ◽  
Mariusz Bidziński ◽  
Nicoletta Colombo ◽  
Anne Floquet ◽  
Maria Jesús Rubio Pérez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Maintenance Treatment ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Phase Iii ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Treatment

TPS5598 Background: Ovarian cancer (OC) is the leading cause of death from gynecologic cancers in US women. Despite high response rates to first-line treatment, ~70% of patients (pts) relapse within 3 years and then remain largely incurable. First-line treatment needs to be improved to achieve long-term remission in pts and improve the cure rate. The Phase III SOLO1 trial showed a meaningful clinical benefit for olap maintenance therapy in newly diagnosed OC pts with a BRCA mutation (Moore et al N Engl J Med 2018). Preliminary data suggest that combining a PD-L1 inhibitor, anti-angiogenic and PARP inhibitor (triplet therapy) may achieve a synergistic antitumor effect. The DUO-O study (NCT03737643) evaluates the efficacy and safety of treatment combinations involving standard-of-care platinum-based chemotherapy (chemo), VEGF inhibitor bev, anti-PD-L1 antibody durva and PARP inhibitor olap, in women with newly diagnosed advanced OC. Methods: Eligible pts for this double-blind, randomized, Phase III study must have newly diagnosed, advanced, high-grade epithelial OC and either have completed primary surgery or plan to have interval debulking surgery. Depending on their tumor BRCA mutation (tBRCAm) status (determined by central test), pts will join one of two independent cohorts. Pts in the non-tBRCAm cohort (n~906) will be randomized (1:1:1) before cycle 2 to: a) chemo + bev + placebo (for 6 cycles) followed by bev (15 mg/kg [total 15 months]) + placebo maintenance treatment (IV and tablets); b) chemo + bev + durva (6 cycles) followed by bev + durva (1120 mg q3w [total 15 months]) + placebo (tablets) maintenance treatment; or c) chemo + bev + durva (6 cycles) followed by bev + durva + olap (300 mg bd tablets [24 months]) maintenance treatment. Pts in the open-label tBRCAm cohort (n~150) will receive 6 cycles of chemo + durva followed by durva + olap maintenance therapy, with optional use of bev. The primary endpoint of progression-free survival will be assessed by modified RECIST 1.1. Key secondary endpoints include overall survival, overall response rate and duration of response. Enrollment began in January 2019. Clinical trial information: NCT03737643.

Indirect treatment comparison of olaparib and talazoparib in germline BRCA-mutated HER2-negative metastatic breast cancer

2021 ◽  
Author(s):  
Charles McCrea ◽  
Robert Hettle ◽  
Poonam Gulati ◽  
Ankush Taneja ◽  
Preety Rajora
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Fixed Effects ◽  
Parp Inhibitor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Significant Difference ◽  
Indirect Treatment

Aim: Two poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib are approved for patients with germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer. Methods: A Bayesian fixed-effects indirect treatment comparison (ITC) analysis was performed to simulate the comparative efficacy (primary outcome of progression-free survival [PFS]) and safety of PARP inhibitor monotherapy. Results: ITC of data from the OlympiAD (olaparib) and EMBRACA (talazoparib) studies suggested no significant difference in efficacy (PFS) between olaparib and talazoparib. However, there were differences in specific adverse events; patients receiving olaparib had a higher rate of nausea and vomiting, while those receiving talazoparib had a higher rate of alopecia and anemia. Discussion: These data support the benefit of the PARP inhibitor class in gBRCAm HER2-negative metastatic breast cancer.

Lived experiences of women reporting fatigue during PARP inhibitor maintenance treatment for advanced ovarian cancer: A qualitative study

2021 ◽  
Vol 160 (1) ◽  
pp. 227-233
Author(s):  
Hanneke Poort ◽  
Anny T.H.R. Fenton ◽  
Embree Thompson ◽  
Margaret M. Dinardo ◽  
Joyce F. Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Qualitative Study ◽  
Lived Experiences ◽  
Maintenance Treatment ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Experiences Of Women

Population-adjusted indirect treatment comparison (PAITC) of maintenance PARP inhibitor (PARPi) with or without bevacizumab versus bevacizumab in women with newly diagnosed ovarian cancer (OC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6052-6052
Author(s):  
Robert Hettle ◽  
Charles McCrea ◽  
Chee Khoon Lee ◽  
Richard Davidson
Keyword(s):  
Phase Iii ◽  
Stage Iii ◽  
Disease Stage ◽  
Effective Sample Size ◽  
Chemotherapy Response ◽  
Newly Diagnosed ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Significant Difference ◽  
Indirect Treatment

6052 Background: In patients (pts) with newly diagnosed OC, bevacizumab (B), PARPi, and PARPi + B have shown benefit as maintenance treatment options after platinum chemotherapy response. Phase III trials have demonstrated longer median progression-free survival (PFS) with PARPi + B (PAOLA-1, olaparib [O]; NCT02477644) vs placebo (P) + B and with PARPi alone (PRIMA, niraparib [N]; NCT02655016) vs P. As there are no randomized head-to-head trials comparing PARPi + B vs PARPi, or PARPi vs B, we performed indirect treatment comparison across these regimens. Methods: Unanchored PAITC was performed with individual pt data (IPD) from a PAOLA-1 subset comprising pts with stage IV disease, stage III with residual disease after primary surgery, inoperable stage III disease, or any patient who received neoadjuvant chemotherapy. Propensity weights were used to match the baseline (BL) characteristics of the PRIMA population. PRIMA dataset was reconstructed using published PFS curves. Both datasets were pooled; treatment efficacy was assessed by weighted Cox regression and Kaplan–Meier methods. PAITC was performed in all pts (biomarker unselected) and the homologous recombination repair deficiency positive (HRD+; cut-off 42) subgroup. Results: 595/806 (266/387 HRD+) PAOLA-1 pts were included. After matching, the effective sample size (ESS) for PAOLA-1 was 532 (242 HRD+; weights 0.241–2.37). Weighted BL data were balanced across cohorts. Conclusions: In biomarker-unselected and HRD+ pts, PAITC suggests that adding O to B significantly improved PFS vs. N or B alone. In biomarker-unselected pts, PAITC results show no significant difference in PFS between N and B. In HRD+, improved efficacy with N appears to translate into improved PFS vs. B alone, although follow-up was <2 years (14 vs 22 months, respectively). Results are hypothesis generating and could guide randomized trial design. Clinical trial information: NCT02477644 and NCT02655016. [Table: see text]

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