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A PDGFRα antibody that had won accelerated approval on a small trial failed to improve survival in the confirmatory study and was withdrawn.
ANNOUNCE, trial NCT02451943 sponsored by Eli Lilly and published in JAMA in 2020, tested the PDGFR-alpha antibody olaratumab with doxorubicin against doxorubicin alone as first-line treatment for advanced soft-tissue sarcoma, and found no improvement in survival or progression, so a drug that had won accelerated approval on a small trial was withdrawn in 2019. It randomised 509 patients and showed no difference in overall survival, its primary endpoint. OnCo links it to sarcomas, doxorubicin and William D. Tap. The record treats it as a frequently cited lesson on phase 2 signals and accelerated approval, and why the earlier randomised phase 2 was so misleading remains the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
Shares Confirmatory trial, Trial lifecycle: from protocol to label, Surrogate endpoint validation: which stand-ins have earned trust, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.
Shares Soft tissue sarcoma of the extremity (localised and advanced), Doxorubicin, Sarcomas (soft tissue, bone, GIST), Cytotoxic chemotherapy.
Shares Soft tissue sarcoma of the extremity (localised and advanced), Doxorubicin, Sarcomas (soft tissue, bone, GIST), Cytotoxic chemotherapy.
Shares Surrogate endpoint, Surrogate endpoint validation: which stand-ins have earned trust, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.
Shares Surrogate endpoint, Surrogate endpoint validation: which stand-ins have earned trust, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.
Shares Surrogate endpoint, Surrogate endpoint validation: which stand-ins have earned trust, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.
Shares Soft tissue sarcoma of the extremity (localised and advanced), Sarcomas (soft tissue, bone, GIST).
Shares Surrogate endpoint, Surrogate endpoint validation: which stand-ins have earned trust, Objective response rate (ORR).