Clinical relevance of reports on early access programs for checkpoint inhibitors in cancer patients: a French retrospective nationwide cohort study

Abstract

Background

To accelerate access to new drugs, France operated an early access program known as Temporary Authorizations for Use (ATUs) until 2021. We analyzed clinical reports submitted under ATUs for immune checkpoint inhibitors (ICIs) and assessed their clinical relevance regarding the approval of ICIs in oncology.

Methods

We included all ICIs granted an ATU by the French drug safety agency, Agence nationale de sécurité du médicament et des produits de santé (ANSM; French National Agency for the Safety of Medicines and Health Products), for patients with cancer between 1 January 2010 and 31 December 2020. We collected patients’ clinical and pharmacovigilance data from ATU reports submitted by pharmaceutical companies and compared these data with those from corresponding pivotal clinical trials (CTs).

Results

The ATUs provided early access to 5807 patients with seven ICIs across 11 cancer indications, 1 of which had no corresponding ATU report. Of the 10 available ATU reports, only 1 included all required data. Clinical follow-up forms were available for 40.5% of patients. Differences in data reporting prevented us from comparing serious adverse events between the CTs and ATU reports. Clinicians and pharmaceutical companies often disagreed on whether ICIs caused 163 permanent treatment discontinuations, with Cohen’s bias- and prevalence-adjusted κ = 0.52, 95% CI 0.33-0.68. Although agreement was almost perfect for 93 nonprogressive tumor deaths (κ = 0.88, 95% CI 0.66-0.97), 29% of ATU patient deaths remained unexplained and were reported as unrelated to treatment by the pharmaceutical companies.

Conclusion

French ATUs facilitated early access to new ICIs for many patients with cancer. However, data attrition hindered effective real-world monitoring.