ICER Evaluates Novel Agents to Prevent Infection with Chemotherapy

Cosela (trilaciclib), used to prevent myelosuppression from chemotherapy, provides a small quality-adjusted life-year compared with no therapy. But with a price of $1,491 per vial, it does not meet current thresholds for cost-effectiveness, according to an updated analysis by the Institute for Clinical and Economic Review (ICER).

Meanwhile, plinabulin, which is development chemotherapy-induced neutropenia (CIN), would achieve common thresholds for cost-effectiveness if priced between $1,100 and $1,600 per dose.

The FDA approved Cosela in February 2021 to decrease the incidence of chemotherapy induced myelosuppression in patients with extensive-stage small cell lung cancer. It would need to be priced at between $430 to $670 per vial to meet ICER’s health-benefit price benchmark.

ICER’s analysis looks at both Cosela and plinabulin, which had been under regulatory review to prevent chemotherapy-induced neutropenia. In December 2021, the FDA issued a complete response letter for plinabulin, saying the single clinical trial that aims to support the application had not been robust enough to demonstrate benefit. The agency asked that an additional clinical trial be conducted.

But given the current data, ICER reviewers believe plinabulin would achieve common thresholds for cost-effectiveness if priced between $1,100 and $1,600 per dose. BeyondSpring Pharmaceuticals, the developer of plinabulin, has not yet announced a price.

ICER’s health-benefit price benchmark is a price range suggesting the highest U.S. price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment.

Steven D. Pearson, M.D.

“ICER had intended to focus this review on an emerging agent, plinabulin, that had promising early data and seemed on track for FDA approval. Trilaciclib, an agent approved in 2021 with a similar intended therapeutic goal, was included in the review upon the recommendation of clinical experts,” Steven D. Pearson, M.D., ICER’s president, said in a press release. “Under the circumstances, we have completed a revision to our draft evidence report following consideration of public comment, but we will not proceed to a full public meeting.”

Chemotherapy often results myelosuppression, including low neutrophil counts (neutropenia), low platelet counts (thrombocytopenia), and low red blood cell counts (anemia), which can put patients at high risk for infection and hospitalization.

Developed by G1 Therapeutics, Cosela is a cyclin-dependent kinase 4 and 6 inhibitor and is administered as a 30-minute infusion before the start of chemotherapy.

ICER analysts said the clinical trial results for Cosela are confusing. Two small phase 2 trials showed Cosela reduced severe neutropenia and severe anemia, but these benefits did not translate into a reduction of hospitalizations, serious adverse events, or deaths due to adverse events. Because of this, ICER analysts judge Cosela to be either comparable to or has a small net health benefit compared with standard of care in patients with extensive-stage small cell lung cancer.

In both first-line and previously treated ES-SCLC, Cosela cost and effectiveness modeling suggests fewer severe myelosuppressive episodes and fewer deaths due to febrile neutropenia, resulting in a small incremental benefit for quality-adjusted life-years (QALYs), equal value life years (evLYs), and life years compared with no myelosuppression prophylaxis.

The quality-adjusted life year is the academic standard for measuring how well different kinds of medical treatments lengthen and/or improve patients’ lives. ICER uses this as a measure of cost effectiveness, as well as equal value life year (evLY), which measures any gains in length of life, regardless of the treatment’s ability to improve patients’ quality of life.

Specifically, due to the relatively short duration of severe events, rarity of febrile neutropenia-related deaths, and limited life expectancy in the ES-SCLC population, incremental gains with Cosela were small. ICER analysts said a discount from current prices between 55% to 71% would be required to meet cost-effectiveness thresholds.

For plinabulin, one phase 3 study assessed the therapy added to pegfilgrastim the prevention of myelosuppression in women undergoing first line therapy for early breast cancer in comparison with pegfilgrastim alone. The combination showed a reduction in severe neutropenia but no significant reduction in febrile neutropenia. There was also a reduction in hospitalizations and fewer grade 4 adverse events.

ICER analysts said there is no data currently of added harm, and they judge that there is moderate certainty of a comparable, small, or substantial benefit for plinabulin added to pegfilgrastim versus pegfilgrastim alone.