The first approval of a checkpoint inhibitor was granted in 2011.
We retrospectively examined all approvals of checkpoint inhibitors (CPIs) granted until January 2019 by FDA. Data regarding the type of approval, cancer type, treatment indication, and endpoints were extracted from the FDA website and from publications.
Fifteen therapeutic indications, including agnostic approvals, among seven CPIs have been approved for solid and hematologic malignancies. Of a total of 41 FDA approvals, nine (21.95%) were approved for the first-line of therapy and 32 (78.05%) for subsequent lines. Fourteen (34.15%) approvals, six (14.63%) in the first-line and eight (19.51%) in the subsequent lines, were granted approval based on overall survival (OS). Twenty-seven (65.85%) approvals (regular and accelerated) were granted based on surrogate endpoints: two (4.88%) using the response rate (RR), 20 (48.78%) using RR and the duration of rsponse (DOR); two (4.88%) using RR, progression-free survival (PFS) and DOR; two (4.88%) using relapse-free survival (RFS), and one (2.44%) using PFS alone. Table shows the distribution of these approvals in the first or subsequent lines. 168PFDA approvals Lines of treatment # for RR (%) # for RR and DOR (%) # for RR, PFS, and DOR (%) # for RFS (%) # for PFS (%) # for OS (%) Total (%) First-line 0 (0) 1 (2.44) 2 (4.88) 0 (0) 0 (0) 6 (14.63) 9 (21.95) Subsequent lines 2 (4.88) 19 (46.34) 0 (0) 2 (4.88) 1 (2.44) 8 (19.51) 32 (78.05) Total 2 (4.88) 20 (48.78) 2(4.88) 2 (4.88) 1 (2.44) 14 (34.15) 41 (100)
Of the total of 41 FDA approvals, 23 (56.10%) were accelerated and 18 (43.90%) regular. Three (7.32%) and 20 (48.78%) were accelerated approvals for the first and subsequent lines, respectively. Six (14.63%) and 12 (29.27%) were regular approvals in the first and subsequent lines, respectively.
RR and DOR were the most frequently approved surrogate endpoints, most often for use in later lines of therapy. The majority of CPI approvals need to confirm the real impact on the patients’ survival, since approximately one third of these approvals were based on the OS. Accelerated approvals based on surrogate endpoints were also preferentially granted for later lines of therapy, where such decisions may have a modest impact on the patients’ survival.
The authors.
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The author has declared no conflicts of interest.