Biomarker testing to guide first-line PARP inhibitor maintenance for patients with advanced ovarian cancer after response to first- line platinum chemotherapy: A cost-effectiveness study (382)

Abstract

Objectives: Multiple poly-ADP ribose polymerase inhibitor (PARPi) maintenance treatment (mTx) options are available for patients with advanced ovarian cancer after response to first-line platinum chemotherapy (PSaOC). Olaparib (O) is an option as monotherapy for patients with BRCA1/2 mutations or in combination with bevacizumab (O+B) for Homologous Recombination Deficiency (HRD+) patients. Meanwhile, niraparib (N) is approved irrespective of biomarker status. This study aimed to evaluate the cost-effectiveness of biomarker testing and treatment with PARP inhibitor mTx in PSaOC patients from the perspective of a US payer. Methods: Ten testing and treatment strategies (Table 1) were evaluated, representing common biomarker testing (none, BRCA or HRD) and mTx (O, O+B, N, B) in approved populations. PAOLA-1 trial data were used to build a lifetime horizon partitioned survival model with four health states, including progression-free (PFS), post 1st progression (PP1), post 2nd progression (PP2), and death. PFS was modeled through parametric mixture survival modeling to a landmark survival point at five years. Patients who remain PFS at year five are assumed to be long-term survivors. Time to PP2 and OS was modeled by fitting standard parametric models, and time on treatment data was informed by respective trials (up to 24m for O, 15m for B, treat to progression for N). The hazard ratio (HR) of PFS for O+B versus N (0.57 for HRD+/ITT; 0.46 for BRCA+) and O+B versus O (0.71 for BRCA+) were obtained from matching adjusted indirect comparison (MAIC) between PAOLA1 and PRIMA, and PAOLA1 and SOLO1. The HRs for OS are informed by PFS benefits and published OS data. The incremental cost-effectiveness ratios (ICERs) were calculated. Results: Strategy 2 (S2, no testing, B) had the lowest cost while S10 (HRD testing, O+B for HRD+ and B for HRD-) had the greatest life- years (LYs) and quality-adjusted life-years (QALYs). All of the niraparib strategies were dominated (i.e., had higher cost, lower LY/ QALYs), compared to at least one other strategy (Table 1). When compared to S2, S8 had lower ICERs than S4 ($41,204 per LY and $48,211 per QALY for S8 vs S2). S10 had an ICER of $66,588 per LY and $82,321 per QALY compared to S8. Conclusions: HRD testing followed by O+B for BRCA-/HRD+, O for BRCA+ and B for HRD- (S8) is highly cost-effective, dominating six strategies (all except 2, 4 &10) and having ICERs < $50,000/QALY compared to the least costly strategy (S2). Replacing O with O+B in BRCA+ patients (S10) improves outcomes, with ICER < 100,000/QALY compared to S8. All strategies involving niraparib were dominated by other approaches. An HRD biomarker-guided approach followed with O±B treatment in HRD+ patients provides the greatest LY and QALYs with good economic value. Objectives: Multiple poly-ADP ribose polymerase inhibitor (PARPi) maintenance treatment (mTx) options are available for patients with advanced ovarian cancer after response to first-line platinum chemotherapy (PSaOC). Olaparib (O) is an option as monotherapy for patients with BRCA1/2 mutations or in combination with bevacizumab (O+B) for Homologous Recombination Deficiency (HRD+) patients. Meanwhile, niraparib (N) is approved irrespective of biomarker status. This study aimed to evaluate the cost-effectiveness of biomarker testing and treatment with PARP inhibitor mTx in PSaOC patients from the perspective of a US payer. Methods: Ten testing and treatment strategies (Table 1) were evaluated, representing common biomarker testing (none, BRCA or HRD) and mTx (O, O+B, N, B) in approved populations. PAOLA-1 trial data were used to build a lifetime horizon partitioned survival model with four health states, including progression-free (PFS), post 1st progression (PP1), post 2nd progression (PP2), and death. PFS was modeled through parametric mixture survival modeling to a landmark survival point at five years. Patients who remain PFS at year five are assumed to be long-term survivors. Time to PP2 and OS was modeled by fitting standard parametric models, and time on treatment data was informed by respective trials (up to 24m for O, 15m for B, treat to progression for N). The hazard ratio (HR) of PFS for O+B versus N (0.57 for HRD+/ITT; 0.46 for BRCA+) and O+B versus O (0.71 for BRCA+) were obtained from matching adjusted indirect comparison (MAIC) between PAOLA1 and PRIMA, and PAOLA1 and SOLO1. The HRs for OS are informed by PFS benefits and published OS data. The incremental cost-effectiveness ratios (ICERs) were calculated. Results: Strategy 2 (S2, no testing, B) had the lowest cost while S10 (HRD testing, O+B for HRD+ and B for HRD-) had the greatest life- years (LYs) and quality-adjusted life-years (QALYs). All of the niraparib strategies were dominated (i.e., had higher cost, lower LY/ QALYs), compared to at least one other strategy (Table 1). When compared to S2, S8 had lower ICERs than S4 ($41,204 per LY and $48,211 per QALY for S8 vs S2). S10 had an ICER of $66,588 per LY and $82,321 per QALY compared to S8. Conclusions: HRD testing followed by O+B for BRCA-/HRD+, O for BRCA+ and B for HRD- (S8) is highly cost-effective, dominating six strategies (all except 2, 4 &10) and having ICERs < $50,000/QALY compared to the least costly strategy (S2). Replacing O with O+B in BRCA+ patients (S10) improves outcomes, with ICER < 100,000/QALY compared to S8. All strategies involving niraparib were dominated by other approaches. An HRD biomarker-guided approach followed with O±B treatment in HRD+ patients provides the greatest LY and QALYs with good economic value.