Authors of a draft report published by the Institute for Clinical and Economic Review evaluating the health outcomes and economic effects of certain tyrosine kinase inhibitors (TKIs) and programmed death 1 (PD-1) immunotherapies in the treatment of advanced non-small-cell lung cancer (NSCLC) expressed "high certainty" that TKIs provide at least a small net health benefit relative to platinum-based chemotherapy.

The report also found that PD-1 therapies also conferred clinical benefit, both in terms of reducing the risk of disease progression or extending time until progression as well as overall survival, ICER's chief scientific officer Dan Ollendorf told BioWorld Today. But, even with existing diagnostic test for PD-1 positivity, "it's difficult to identify which patients will benefit," he said.

The effects of both classes of agents were evaluated in epidermal growth factor receptor positive (EGFR+) NSCLC, while PD-1 agents were also evaluated in EGFR-negative NSCLC.

For its examination of TKIs, ICER evaluated multiple studies of drugs in the class, the current standard of care for EGFR+ NSCLC: Boehringer Ingelheim GmbH's Giotrif (afatinib), Roche AG's Tarceva (erlotinib) and Astrazeneca plc's Iressa (gefitinib).

ICER's conclusions on TKIs suggest that not only could they have anywhere between a small benefit and a substantial benefit, but also that sequencing of treatment with drugs of the class may not have a significant impact on patient outcomes. "The reason that we didn't have a more certain conclusion was because the trials of those agents, compared to chemotherapy, did not show a survival benefit," Ollendorf said. The reason for that, ICER stated, is because the trials allowed for crossover between arms when patients' cancers progressed. "The most likely conclusion is that TKIs improve survival regardless of when they're given to the patient," said Ollendorf.

Among PD-1 agents, the group focused on Bristol-Myers Squibb Co.'s Opdivo (nivolumab) and Merck & Co Inc.'s Keytruda (pembrolizumab), which are antibodies to PD-1, as well as Genentech Inc.'s Tecentriq (atezolizumab), an antibody to PD-L1. Making explicit comparisons among the PD-1s was difficult, Ollendorf said, because they use different diagnostics to test for PD-1 levels. "So, we're not able to distinguish the effects of these different drugs in PD-1 positive patients because of the different cutoffs and different assays used."

ICER, founded in 2006 as an academic research project at Harvard Medical School, is now an independent nonprofit organization funded primarily by nonprofit philanthropic foundations. Manufacturer grants, contracts and contributions also fund its work, but to a lesser extent. It took on its review of the NSCLC space due to rising interest among clinicians, patient groups and payers on two fronts: Patient groups sought an understanding of how well checkpoint inhibitors are working, what sequencing works best, and where the evidence to support that decision-making lies.

The draft report will be open to public comment until Sept. 16, after which it will serve as the basis for deliberation and discussion at an upcoming public meeting of the Midwest Comparative Effectiveness Public Advisory Council, an independent advisory to ICER, on Oct. 20. During that meeting, the council will vote on key questions raised in the reports, and a policy round table will discuss recommendations to apply the evidence to policy and practice.

Current draft voting questions cover both TKIs and PD-1 therapies. Regarding TKIs, for instance, the council will be asked to vote "yes" or "no" on the question of whether, in patients with EGFR+ advanced NSCLC, there is adequate evidence to distinguish the net health benefit among the TKIs erlotinib, gefitinib and afatinib. The report suggests that evidence on first-line TKI therapy for EGFR+ advanced NSCLC is inadequate to distinguish between the three therapies on patient-important outcomes such as overall survival and quality of life. Council members will also be asked to assess as "low," "intermediate," or "high" the "care value" of PD-1 immunotherapy in light of its additional costs, benefits, disadvantages and "contextual considerations."