ICER council votes on effectiveness, value of NSCLC therapies

The Midwest Comparative Effectiveness Public Advisory Council program of the Institute for Clinical and Economic Review yesterday generally voted in favor of the net-health benefit and long-term value of tyrosine kinase inhibitors for the treatment of non–small cell lung cancer.

Although Midwest Comparative Effectiveness Public Advisory Council (CEPAC) generally voted that individual PD-1 inhibitors provide a greater net-health benefit than docetaxel in their approved settings, the council tended to vote that these agents had low to intermediate long-term monetary value.

Steven Pearson

“There has been tremendous innovation recently in the treatment options available for patients with NSCLC,” Steven Pearson, MD, MSc, president of Institute for Clinical and Economic Review (ICER), said during the meeting. “Those innovations are driving really important questions about the overall paradigm of care for these patients. The innovation is often expensive, and this always raises questions about the ultimate value and the affordability of different treatments of different kinds of patients.

“We are dealing with a health care system that currently creates a lot of pressure on individual patients for affording their care, and it clearly is providing a broader pressure on health system and state and federal budgets,” Pearson added.

ICER thus sought to provide an independent review of the evidence within NSCLC treatment for public discussion.

CEPAC voted on the net-health benefit and cost-effectiveness of three TKIs for NSCLC — afatinib (Gilotrif, Boehringer Ingelheim), erlotinib (Tarceva; Genentech, Astellas Pharma) and gefitinib (Iressa, AstraZeneca) — and three immunotherapies, atezolizumab (Tecentriq, Genentech/Roche), nivolumab (Opdivo, Bristol-Meyers Squibb) and pembrolizumab (Keytruda, Merck), based on a draft ICER report published in September and presented at the meeting.

The panel voted 2 to 8 whether evidence was adequate to distinguish the net-health benefit among the TKIs for EGFR–positive NSCLC, suggesting that evidence does not exist to distinguish between each of these drugs.

However, they voted 10 to 1 in favor of a TKI providing benefit over a platinum doublet for the first-line treatment of EGFR–positive NSCLC. Nine members said there was intermediate long-term value of TKI therapy, and one member said TKIs had high value.

All panel members voted there was not enough evidence to distinguish among nivolumab, pembrolizumab and atezolizumab for EGFR–negative, progressive NSCLC.

“These drugs only work for a minority of patients,” David Rind, MD, MSc, chief medical officer for ICER, said during the meeting. “A minority can be 20% to 45%, and in those patients it works for, there are remarkable benefits. But, compared to each other, there is a problem because they were each looking at different populations. You can only compare these drugs each to docetaxel, from our point of view. We don’t think we have adequate evidence to compare them against each other, simply because the populations looked at were different.”

The votes were generally positive that among patients with EGFR–negative NSCLC who experienced progression on a platinum doublet, nivolumab (8 vs. 2), pembrolizumab (10 vs. 0) and atezolizumab (8 vs. 2) provide a net-health benefit compared with docetaxel. These settings applied to their approved indications — or irrespective of PD-L1 level for nivolumab and at least a 50% PD-L1 expression for pembrolizumab.

However, the council voted on atezolizumab for patients with certain levels of PD-L1 expression based on phase 2 data. The drug was approved 2 days prior to the meeting for patients with progressive disease, regardless of their PD-L1 expression, but ICER did not have adequate time to include these data in their report.

Based on an incremental cost-effectiveness ratio of $415,950 (range, 138,508-604,246) and 0.83 (range, 0.54-3.14) quality-adjust life years (QALYs) gained, the committee voted nivolumab had low (6 votes) or intermediate (4) long-term monetary value compared with docetaxel.

More members voted pembrolizumab had intermediate long-term value (intermediate, 7; low, 3), based on an incremental cost-effectiveness ratio of $240,049 (range, 89,158-392,239) and 1.41 (0.8-4.76) QALYs gained.

Six members voted atezolizumab had intermediate value, and four voted it had low value (incremental cost-effectiveness ratio, $219,179; range, 68,144-518,560; QALYs, 1.08; range, 0.59-4.24). However, the council noted this vote does not reflect the current indication.

“If we looked at the cost-effectiveness for the now-labeled indication [of atezolizumab], we’d be taking the results from the phase 2 trial, POPLAR, which showed no benefit in patients who were PD-L1 negative, and then using the whole population, where there was a benefit, but smaller,” Rind said. “The whole-population benefit from the phase 3 trial, that included it being effective in PD-L1–negative patients, is less than [the benefit] in the subpopulation that we looked at here. So, the incremental cost-effectiveness ratio would be worse than the number we came up with, because we looked at a population more like the pembrolizumab population, but it will end up looking more like the nivolumab population, although we still need to do the calculations.”

For patients without driver mutations and PD-L1 positivity of at least 50%, the council voted unanimously that first-line use of pembrolizumab has a net-health benefit over docetaxel.

For patients with EGFR–positive disease that progressed after a platinum doublet, the council voted 2 to 8 that a PD-1 immunotherapy had a greater net-health benefit than docetaxel.

This evidence can be applied to clinical practice, medical policies, consideration around pricing, research and patient engagement, Pearson said.

“We are looking for ways for drugs to be covered, but where we can enroll providers into pathway-based programs that give them incentives for using more cost-effective therapies,” Jay Moore, MD, senior clinical officer at Anthem BlueCross BlueShield, said during a policy roundtable. “As an example, even though we cover all of the PD-1–targeted drugs, there are some which are on our pathway and some which are not.

“If a provider and their patient choose to [use] a particular drug that may not be preferred to us, we aren’t going to say no,” Moore added. “We will cover it and it will get paid, just like a regular benefit. However, if they use one of the preferred drugs, are their incentives that we can then provide to the provider and/or the patient to use the drugs proven to be equally effective, but have different value propositions? We are making sure the doctor has the choice to treat their patient as they see fit, but the cost is still something that is kept in mind from the patient and physician perspective.”

A final ICER report on the value and efficacy of these treatments for NSCLC based on this meeting is expected on or before Nov. 3. – by Alexandra Todak

Disclosure: Pearson and Rind report employment with ICER. Moore reports employment with Anthem BlueCross BlueShield.