Durvalumab's High Costs Hinder Global Uptake for Stage III NSCLC Maintenance Therapy

Financial data reported today in JAMA Network Open from an international study covering the US, Brazil, Singapore, and Spain show that durvalumab largely remains a cost-prohibitive treatment option for maintenance therapy of unresectable, locally advanced stage III non–small cell lung cancer (NSCLC) following combined chemoradiotherapy. This conclusion was reached after considering each country’s willingness-to-pay (WTP) threshold per quality-adjusted life-year (QALY).¹

Global barriers to durvalumab include not only price, but lack of patient access, health system approval, patient access, reimbursement, and testing for PD-L1 tumor proportion score | Image Credit: Ян Заболотний-stock.adobe.com

“While the regimen has high-quality, phase 3 trial evidence backing its use, limitations of its global uptake include cost, health system approvals, access, and patient eligibility,” the study investigators wrote. “For example, the European Medicines Agency only approved the regimen for patients whose tumors harbor [PD-L1] scores of 1% or higher.”

To carry out this analysis from June 1, 2022, to December 27, 2023, the investigators used a Markov/US base-case model to compare the treatment’s lifetime cost-effectiveness vs placebo, and they used 5-year outcomes data from the PACIFIC trial, as well as patient-leval data from the PACIFIC (NCT02125461), KEYNOTE-189 (NCT02578680), ADAURA (NCT02511106), ALEX (NCT02075840), and REVEL (NCT01168973). These studies investigated patient outcomes in the settings of unresectable or metastatic nonsquamous disease, carcinoma, being treatment naïve, and second-line treatment.^2-6

Compared with placebo maintenance therapy over 10 years, primary outcomes were life-years, QALYs, lifetime costs, and incremental cost-effectiveness ratios (ICERs) per country-specific WTP thresholds . Per QALY, these thresholds (all are reported in US$) were $150,000 for the US; $107,069 for Spain; $55,288 for Singapore; and $22,251 for Brazil. The investigators considered costs for diagnosis, drug acquisition, drug administration, postprogression therapies, monitoring, end-of-life care, adverse events, and supportive care.

Overall survival (OS) was a median 45 (95% CI, 42.5-47.5) months, and progression-free survival (PFS), 31.9 (95% CI, 29.0-34.8) months, vs 37.4 (95% CI, 33.7-41.1) months and 19.9 (95% CI, 16.2-23.4) months, respectively, with placebo. For the US base case, OS was 51.1 (95% CI, 48.8-53.4) months and PFS, 37.9 (95% CI, 35.4-40.5) months for durvalumab vs 39.3 (95% CI, 37.5-41.0) months and 19.9 (95%CI, 18.2-21.5) months, respectively, for placebo. Per the PACIFIC trial,² this is the equivalent of 0.50 (95% CI, 0.45-0.55) QALYs gained with durvalumab vs placebo.

ICERs per QALY following durvalumab treatment vs placebo in each country were greater than the country’s WTP threshold:

• In the US: $228,788 (95% CI, $207,989-$254,208), for an incremental cost per 1 life-year saved of $116,332 (95% CI, $105,594-$129,502
• In Singapore: $153,461 (95% CI, $135,753-$168,076), for an incremental cost per 1 life-year saved of $76,315 (95% CI, $69,434-$92,076)
• In Brazil: $141,146 (95% CI, $127,830-$157,558), for an incremental cost per 1 life-year saved of $71,947 (95% CI, $65,040-$80,495)
• In Spain: $125,193 (95% CI, $114,400-$138,233), for an incremental cost per 1 life-year saved of $64,212 (95% CI, $58,979-$71,091)

Additional probabilistic sensitivity analyses of current costs and WTP thresholds showed meager chances of durvalulmab being cost-effective in any of the 4 countries covered here: 7.2%, 0%, 0%, and 31%, respectively, in the US, Brazil, Singapore, and Spain.

Singapore was the sole country to offer an industry-sponsored access program for durvalumab through which 500 mg vials were offered each month at buy 1/get 2 free and 120 mg vials at buy 2/remainder free. Considering a cost of $1000/vial, the average monthly cost of $6.38/mg, according to the study authors, works out to be $4.23/mg with a 33.7% discount. This equates to a 74.9% cost-effectiveness probability for durvalumab and an incremental cost per 1 life-year saved of $23,290 (95% CI, $21,189-$28,855).

“To our knowledge, this analysis represents the latest and most comprehensive evaluation of durvalumab using 5-year outcomes data in multiple clinical practice country frameworks,” the authors wrote.

Although their analysis focused on cost, they highlighted that this is not the only barrier to wider global use of durvalumab. Other significant uptake barriers are lack of health system approval, patient access, no reimbursement through public health systems, and lack of testing for PD-L1 tumor proportion score to determine patient eligibility.

They go on to note that immunotherapy pricing overall is high, with adverse effect felt throughout health care systems—patients, clinicians, and budgets alike—due to the high cost-benefit thresholds.

“The primary conclusion of our analysis is the increased cost-effectiveness of an industry-sponsored access program to convert cost-prohibitive therapies into cost-effective treatments,” the study authors wrote. “On the regulatory side, expedited approvals in high-income countries, can lead to more rapid approvals and access in low- and middle-income countries, although it is unclear whether this strategy results in achieving cost-effective pricing.”

References

1. Kareff SA, Han S, Haaland B, et al. International cost-effectiveness analysis of durvalumab in stage III non–small cell lung cancer. JAMA Netw Open. Published online May 30, 2024. 2024;7(5):e2413938. doi:10.1001/jamanetworkopen.2024.13938

2. A global study to assess the effects of MEDI4736 following concurrent chemoradiation in patients with stage iii unresectable non-small cell lung cancer (PACIFIC). ClinicalTrials.gov. Updated October 10, 2023. Accessed May 29, 2024. https://www.clinicaltrials.gov/study/NCT02125461

3. Study of pemetrexed+platinum chemotherapy with or without pembrolizumab (MK-3475) in participants with first line metastatic nonsquamous non-small cell lung cancer (MK-3475-189/KEYNOTE-189). ClinicalTrials.gov. Updated July 20, 2023. Accessed May 29, 2024. https://www.clinicaltrials.gov/study/NCT02578680

4. AZD9291 versus placebo in patients with stage IB-IIIA non-small cell lung carcinoma, following complete tumour resection with or without adjuvant chemotherapy (ADAURA). ClinicalTrials.gov. Updated July 27, 2023. Accessed May 29, 2024. https://clinicaltrials.gov/study/NCT02511106

5. A study comparing alectinib with crizotinib in treatment-naive anaplastic lymphoma kinase-positive advanced non-small cell lung cancer participants (ALEX). ClinicalTrials.gov. Updated May 14, 2024. Accessed May 29, 2024. https://www.clinicaltrials.gov/study/NCT02075840

6. A study of chemotherapy and ramucirumab versus chemotherapy alone in second line non-small cell lung cancer (NSCLC) participants who received prior first line platinum-based chemotherapy. ClinicalTrials.gov. Updated September 25, 2019. Accessed May 29, 2024. https://www.clinicaltrials.gov/study/NCT01168973