640P - Tumor response rate for hematologic and solid cancer drugs with FDA approval supported by single-arm trials

Background

Single-arm phase 1/2 trials test new cancer drugs’ safety and establish first evidence of tumor response. The tumor response rate (RR) is measured as radiologic tumor shrinkage by -30% in size (solid cancers) or hematologic regression (hematologic cancers). For promising drugs with substantial RRs in early single-arm trials, the US Food and Drug Administration (FDA) may grant patients fast access using expedited approval. With one-third of drugs approved based on phase 1/2 trials, we meta-analyzed tumor response in single-arm trials for cancer drugs.

Methods

We identified 79 cancer drugs with 163 indications (86 hematologic, 77 solid) approved by the FDA based on single-arm trials (2000-2022). Data were collected from Drugs@FDA, clinicaltrials.gov, and associated peer-reviewed publications. The primary outcomes of interest collected for each trial were the tumor-specific RR and duration of response. RRs were measured by RECIST for solid cancers and by multiple established measures for hematologic cancers. RRs were meta-analyzed with random-effect models.

Results

The mean RR was 46.8% (95%CI 43.1-50.6, p<0.001) with a median response duration of 10.7 months). RRs were higher for hematologic than solid cancers (53.4% vs. 40.3%, p<0.001). Particularly high RRs were observed for thyroid cancer (71.5%), CML (70.2%), and Hodgkin lymphoma (69.9%), whilst lowest RRs were for cervical cancer (18.9%), HNSCC (16.1%), and esophageal/gastric cancer (13.6%). Among solid tumors, greater RRs were measured for targeted agents (48.40%), biomarkers (47.3%), first-line treatments (53.4%), orphan diseases (46.5%), and breakthrough therapy designations (47.3%). Results were consistent for hematologic cancers.

Conclusions

Tumor response rates in pivotal single-arm trials appear substantial – nearly half of the patients (46.8%) receiving a new cancer drug show a positive response for ca. 11 months. These data inform patients and physicians on new drugs’ expected benefits and represent a benchmark for future development efforts. However, drugs showing promising RRs must undergo validation in large, confirmatory randomized-controlled trials to demonstrate an improvement in patient survival.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.