Consolidation therapy with durvalumab (Imfinzi) may be a cost-effective option for patients with inoperable, stage III non-small cell lung cancer (NSCLC) whose disease has not progressed after definitive chemoradiotherapy, according to a simulation model.
Compared with no consolidation therapy, adding durvalumab had an estimated incremental cost-effectiveness ratio (ICER) of $67,421 per quality-adjusted life-year (QALY), Chung Yin Kong, PhD, of Massachusetts General Hospital in Boston, and colleagues reported.
The cost per QALY was derived from an estimated mean cost of $185,944 for a gain of 2.34 QALYs per patient not receiving consolidation therapy, compared with $201,563 for a gain of 2.57 QALYs in patients receiving consolidation therapy with durvalumab. Cost-effectiveness was based on a willingness-to-pay threshold of $100,000 per QALY.
“Durvalumab provides a promising opportunity for delaying recurrence and potentially improving the likelihood of cure in a cost-effective manner, making it the preferred method of treatment from a health economics standpoint,” they wrote in JAMA Oncology.
Lung cancer has been the leading cause of cancer mortality in the U.S. for the past 3 decades, and the 5-year survival rate is only 15% for patients with unresectable stage III NSCLC who go on to receive chemoradiotherapy.
The researchers estimated that using this treatment strategy for all eligible patients could add $768 million to national cancer spending in year 1, corresponding to a 0.8% increase in spending, based on a reported mean increase in total cancer spending of 7% per year between 2000 and 2015. The projected annual budgetary consequence would decrease to $241 million in year 5.
Based on progression-free survival evidence from the phase III PACIFIC trial, the selective PD-L1 inhibitor durvalumab became the first immunotherapy approved by the FDA (in February of this year) for the adjuvant treatment of patients with unresectable stage III NSCLC with no progression after definitive chemoradiotherapy.
Subsequent PACIFIC results reported at the World Conference on Lung Cancer in late September found that at a median follow-up of 25.2 months, patients on the PD-L1 inhibitor had a statistically significant 32% lower risk of death compared with those on placebo (median improvement was not yet reached).
Noting that lung cancer is always a “grave diagnosis” and highlighting the poor 5-year survival in later stages of diagnosis, Jeremy Warner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, told MedPage Today that the PACIFIC trial results are welcome, especially given the mixed results of prior trials — such as SWOG 0023 — that attempted to add consolidative therapy in this setting.
“One caveat is that standard-of-care immunotherapy (nivolumab [Opdivo] or pembrolizumab [Keytruda]) for metastatic NSCLC wasn’t approved until about a year into the conduct of this study, so it isn’t entirely clear that everyone in the placebo arm might have had the opportunity to have immunotherapy at the time of progression,” said Warner, who was not involved in either of the two studies.
“Nevertheless, the robust and statistically significant improvement in overall survival alone would certainly convince me to consider consolidative durvalumab as a new standard of care, and that it is also shown to be cost-effective is reassuring,” he continued. “It should be noted that some 15% of the patients in the durvalumab arm discontinued treatment due to adverse events, and toxicity of immunotherapy must also be a consideration when considering the value of this treatment approach.”
For the current study, the researchers used a decision analytic microsimulation model developed in an academic medical setting to compare two post-chemoradiotherapy strategies: one where all patients receive no therapy until progression, and the other where patients receive durvalumab consolidation until progression or for a maximum of 1 year.
Potential costs were calculated by applying the proportion of patients who were diagnosed with NSCLC and received chemoradiotherapy to the projected number of annual new cases of NSCLC diagnosed in stage III for 2018 to 2022, multiplied by the mean difference in annual cost between the strategies over that 5-year period. Simulated conditions were matched to those of the PACIFIC phase III trial (e.g., patients were disease free following chemoradiotherapy) and to reasonable treatment strategies for metastatic NSCLC.
The modest difference in cost between consolidation and no consolidation in the model can be explained by the clinical consequences of immunotherapy combination trials for first-line treatment of metastatic NSCLC, which can extend up to 2 years, while consolidation therapy with durvalumab is limited to 1 year, they explained.
Limitations noted by the group included basing progression rates on survival data from multiple trial populations with different treatment regimens from that specified in this model; the assumption for budget analysis that patients did not progress during chemoradiotherapy, which may have caused overestimation of the number of eligible patients; and that results may change given that overall survival data for the PACIFIC trial are not yet known.
Ongoing research should aim to identify patient populations who respond best to immunotherapy and experience the fewest adverse events, potentially through improved biomarker selection, concluded the researchers.
This study was supported by grants from the National Institutes of Health.
Yin Kong had no disclosures. One co-author reported relationships with Bristol-Myers Squibb, Pfizer, Merck, Genentech/Roche, Ariad/Takeda, Incyte, Agios, Amgen, Loxo, and Theravance.