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

BackgroundSingle-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.MethodsWe 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.ResultsThe 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.ConclusionsTumor 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.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.