Abstract
Background
Obinutuzumab (GA101; G) in combination with chemotherapy followed by G maintenance (G+chemo) has demonstrated superior progression-free survival (PFS) relative to the combination of Rituximab and chemotherapy followed by R maintenance (R+chemo) for previously untreated patients with follicular lymphoma (FL) in the phase III GALLIUM clinical trial (NCT01332968) (Hiddemann et al., European Hematology Association, 2017). The net clinical benefit and economic value of G+chemo vs. R+chemo in a previously untreated FL patient population have not been formally evaluated. The objective of this study was to estimate the cost-effectiveness of G+chemo vs. R+chemo based on results of the GALLIUM trial.
Methods
In the GALLIUM trial, patients received chemotherapy (8 x 21-day cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], 8 x 21-day cycles of cyclophosphamide, vincristine, and prednisone [CVP], or 6 x 28-day cycles of bendamustine) and were randomized to receive either R 375mg/m2 on Day (D) 1 of each cycle or G 1000mg on D1, 8 and 15 of Cycle 1 and D1 of subsequent cycles. Patients with a complete response or partial response at the end of induction as per modified Cheson criteria received R or G every 2 months for 2 years or until disease progression. We developed a Markov model that utilized the GALLIUM trial's independent review committee (IRC) assessed progression-free survival (PFS), and post-progression survival (PPS) to model overall survival (OS). Drug utilization, treatment duration and adverse events were based on trial data. Costs include drugs, adverse events, monitoring and follow-up care upon disease progression; health care costs were based on Medicare reimbursements and drug costs were July 2017 average sale price (ASP) for intravenous therapies or wholesale acquisition cost (WAC) for oral therapies used post-progression. Utility estimates were based on the GALLIUM trial data and published literature to derive the quality of life impact and compute the quality-adjusted life years (QALY). Sensitivity analyses were conducted to assess the key drivers of the model and uncertainty in the results.
Results
Treatment with G+chemo led to an increase in quality-adjusted life years (QALYs) relative to R+chemo of 0.79 (95% Credible Range (CR) 0.19, 1.36) (Table 1). The total cost of G+chemo was $217,000 and R+chemo was $215,100 resulting in an incremental cost of $1,800 (95% CR: -$7,800, $10,000). The average total cost was greater for G+chemo due primarily to increased drug and administration costs ($137,100 for G+chemo vs. $126,300 for R+chemo), however this was largely offset by cost-savings for disease progression of -$10,100 ($75,700 for G+chemo vs. $85,600 for R+chemo). Adverse event costs were higher for G+chemo ($4,200) vs. R+chemo ($3,300). The incremental cost-effectiveness ratio was $2,249 per QALY gained. In probabilistic sensitivity analyses, there was a 98% and 99% probability that G+chemo was cost-effective versus R+chemo at the $50,000 and $100,000 per QALY thresholds, respectively. There was a high probability G+chemo was cost effective even when all parameters in the model were varied.
Conclusions
Our US-based analysis suggests that treatment with G+chemo compared to R+chemo is cost-effective in previously untreated patients with FL. The cost-effectiveness of G+chemo is driven by delaying expensive progression treatments and increasing quality adjusted life years. In conclusion, G+chemo vs. R+chemo in previously untreated FL patients is very likely cost effective in the US.
Guzauskas: Genentech, Inc.: Consultancy. Masaquel: Genentech Inc.: Employment, Other: I Receive Roche stock options. Thuresson: F. Hoffmann-La Roche Ltd: Employment. Li: Genentech: Employment, Equity Ownership. Reyes: Genentech Inc.: Employment, Equity Ownership. Veenstra: Genentech, Inc.: Consultancy.
