Only two of 23 indications for six FDA-approved immuno-oncology agents showed durable survival benefits under the revised ASCO value framework, according to study findings.
“There are [two] possible reasons for this,” Omer Ben-Aharon, MBA, MHA, from the department of management and health system management program at Bar-Ilan University in Israel, and colleagues wrote. “The first is that the public excitement concerning durable survival with immuno-oncology may lack sufficient supporting data. The second is that the ASCO value framework may be insufficiently calibrated to reward durable survival benefits.”
ASCO developed a conceptual framework to measure the value of cancer treatment options.
An update of this framework awarded bonus points to regimens that improved durable survival — defined as a 50% relative improvement in the number of patients alive at twice the median OS or PFS time point for the control regimen and if a minimum 20% of patients receiving the control regimen are still alive at that point.
A framework’s ability to account for durable survival — demonstrated by plateaus on survival curves — is important in the new era of immuno-oncology agents. Researchers sought to measure which immuno-oncology agents approved by the FDA met the durable survival threshold defined by the updated ASCO framework.
Researchers extracted data from the FDA hematology/oncology approval notifications for the following agents: ipilimumab (Yervoy, Bristol-Myers Squibb), pembrolizumab (Keytruda, Merck), nivolumab (Opdivo, Bristol-Myers Squibb), atezolizumab (Tecentriq, Genentech), avelumab (Bavencio, EMD Serono) and durvalumab (Imfinzi, AstraZeneca).
They collected the data required for the ASCO framework for each agent, including improvement in the number of patients alive with the test regimen and survival rate with standard treatment.
The FDA approved 23 indications for these agents for metastatic solid tumors between March 2011 and August 2017. Ten of the approvals were based on survival endpoints and 13 on response rates.
Only three of these indications reached the required 20% survival rate for the control group: ipilimumab for second-line melanoma treatment (22%), nivolumab for first-line melanoma treatment (25%), and nivolumab for second-line squamous non-small cell lung cancer treatment (22%).
Nine indications met the required 50% improvement in the number of patients alive in the test regimen compared with the standard regimen: pembrolizumab for first-line NSCLC treatment (140%), atezolizumab for second-line NSCLC treatment (132%), pembrolizumab for first-line melanoma treatment (101%), pembrolizumab for second-line urothelial carcinoma treatment (100%), nivolumab for second-line nonsquamous NSCLC treatment (94%), nivolumab for first-line melanoma treatment (89%), nivolumab for second-line squamous NSCLC treatment (76%), ipilimumab for second-line melanoma treatment (71%), and nivolumab for second-line head and neck squamous cell carcinoma treatment (69%).
Only two indications met both requirements and had OS as a primary endpoint, receiving the maximum potential score of 20 points: ipilimumab for second-line melanoma and nivolumab for second-line squamous NSCLC.
A limitation of the study included the reliance on therapeutic outcomes reported from clinical studies and FDA approvals.
“The selective population participating in these trials might lead to survival results that differ from outcomes in the general population. However, we are dealing with very new treatments,” the researchers wrote, adding that shorter follow-up periods also limited the available data.
Lowell E. Schnipper
Richard L. Schilsky
The researchers suggested amending the ASCO framework to remove or adjust the required threshold for survival with standard care and shift focus to the difference between two treatments. However, this approach might benefit treatments in which few patients survived in the control group, highlighting the “delicate balance between the need for statistical significance and the need to identify treatments with the potential for durable survival,” the researchers added.
Whether value frameworks account for durable survival remains an important issue among new immuno-oncology agents as more are developed, according to Lowell E. Schnipper, MD, chief of hematology and oncology at Beth Israel Deaconess Medical Center and a HemOnc Today Editorial Board Member, and Richard L. Schilsky, MD, FACP, FASCO, chief medical officer of ASCO. However, the need for innovation that leads to long-term survival is of greater importance, suggesting the bar should be set even higher, they wrote in a related editorial.
“The ASCO value framework is an iterative endeavor,” Schnipper and Schilsky wrote. “As clinical science changes, evaluative tools with which to assess comparative clinical efficacy will evolve. The emphasis must be on raising the bar for outcomes as we design clinical trials and assess the net health benefits and value of new treatments.” – by Melinda Stevens
Disclosure: The authors, Schnipper and Schilsky report no relevant financial disclosures.