scholarly journals Population-adjusted indirect treatment comparison of the SOLO1 and PAOLA-1/ENGOT-ov25 trials evaluating maintenance olaparib or bevacizumab or the combination of both in newly diagnosed, advanced BRCA-mutated ovarian cancer

2021 ◽  
Vol 157 ◽  
pp. 415-423
Author(s):  
Ignace Vergote ◽  
Isabelle Ray-Coquard ◽  
Daniel M. Anderson ◽  
Guilherme Cantuaria ◽  
Nicoletta Colombo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Newly Diagnosed ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Indirect Treatment

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.

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]

scholarly journals An indirect treatment comparison of the efficacy of semaglutide 1.0 mg versus dulaglutide 3.0 mg and 4.5 mg

2021 ◽  
Author(s):  
Richard E. Pratley ◽  
Andrei‐Mircea Catarig ◽  
Ildiko Lingvay ◽  
Adie Viljoen ◽  
Abby Paine ◽  
...  
Keyword(s):  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Indirect Treatment
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