Sie sind bereits registriert?
Loggen Sie sich mit Ihrem Universimed-Benutzerkonto ein:
Sie sind noch nicht registriert?
Registrieren Sie sich jetzt kostenlos auf universimed.com und erhalten Sie Zugang zu allen Artikeln, bewerten Sie Inhalte und speichern Sie interessante Beiträge in Ihrem persönlichen Bereich zum späteren Lesen. Ihre Registrierung ist für alle Unversimed-Portale gültig. (inkl. allgemeineplus.at & med-Diplom.at)
Phase 1 Oncology Trials: Improved Outcomes Over Time
Phase 1 trials are frequently viewed as having a low probability of benefiting an individual patient, despite the novelty of agents being investigated. Often forgotten is that these trials are primarily designed to define the optimal dose of a drug to take forward for further development. A secondary goal is to identify signals of antitumor activity. Although the fraction of novel agents that go on to FDA-approval remains modest, the collective progress made with phase 1 trials deserves re-evaluation.
Investigators analyzed patient-level data from the Cancer Therapy Evaluation Program of the National Cancer Institute–sponsored investigator-initiated phase 1 trials for solid tumors between 2000 and 2019, with particular attention to high-grade toxicity and objective tumor response. A total of 465 studies that involved almost 14,000 patients and 261 agents were included; most trials (69%) evaluated combination therapy. Data were analyzed in 5-year intervals.
The overall treatment-related death rate (grade 5 toxicity) was 0.7% across all intervals. The most common grade 3–4 toxicities were neutropenia (16.9%), lymphopenia (8.9%), thrombocytopenia (7.1%), and anemia (6.5%). The overall response rate (ORR) was 12.2%, with infrequent complete responses (2.7%). The ORR increased from 9.6% during the first interval to 18.0% during the last; the complete response rate changed only from 2.5% to 4.3%. Combination therapy was associated with higher ORR than monotherapy (15.8% vs. 3.5%).
Interestingly, ORRs differed depending on the malignancy and were highest in bladder, lung, and kidney cancer and melanoma. Specific agents had differential benefits; for example, ORRs with anti-angiogenic agents were highest in bladder, colon, kidney, and ovarian cancer.
Phase 1 trials often get a bad rap as being unlikely to benefit patients while exposing them to significant toxicity. This report is reassuring, first in its finding of a low probability of life-threatening toxicity associated with phase 1 trials. Second, in showing that in a population of patients often refractory to standard therapies, ORRs have increased over time in these trials, with certain malignancies benefiting more than others.
Chihara D et al.
Title: Early drug development in solid tumours: Analysis of National Cancer Institute-sponsored phase 1 trials.
Source: Lancet 2022 Aug 13; [e-pub]. (Abstract/FREE Full Text)