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Two thirds of women treated on the KEYNOTE-522 regimen have no tumour left at surgery and about 92 percent of them are alive without relapse at five years, yet all receive nine more cycles of pembrolizumab. Trials are now testing whether the best responders can stop early, skip the anthracycline, or in lymphocyte-rich stage I tumours skip chemotherapy altogether.
KEYNOTE-522 produced pathological complete response in 64.8 percent of patients and the CTNeoBC pooled analysis shows complete responders in triple-negative disease have an event-free survival hazard ratio of 0.24; Leon-Ferre's pooled cohort of 1,966 chemotherapy-untreated patients found five-year distant recurrence-free survival of 94 percent in stage I tumours with lymphocytes of 50 percent or more. Against this, the full regimen carries grade 3 or higher adverse events in 78 percent, permanent endocrine toxicity from pembrolizumab, and anthracycline cardiotoxicity and leukaemia risk. OptimICE-pCR (1,295 patients, primary completion May 2033) randomises complete responders to adjuvant pembrolizumab or observation; SCARLET (2,400, March 2033) tests an anthracycline-free regimen; St Gallen 2023 framed intensity and duration as the central problem. A prospective trial of chemotherapy omission in lymphocyte-rich stage I disease has not started.
A second publication from the KEYNOTE-522 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.
The evidence behind the stage I de-escalation statement on the triple-negative page: an ordinary haematoxylin and eosin slide identifies a fifth of patients whose outcome without chemotherapy matches treated cohorts. A prospective trial of chemotherapy omission is the missing step.
St Gallen is where de-escalation questions in triple-negative disease (who needs the full KEYNOTE-522 regimen, who can skip adjuvant pembrolizumab) are first put to a vote; the 2023 panel framed intensity and duration as the central problem.
This is the paper Europe PMC returns for registry id NCT03036488 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-522 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
The basis of the US accelerated approval pathway on pathological complete response that KEYNOTE-522 and neoadjuvant trials since have used, together with the warning that a higher response rate in a trial is a promise, not a proof, of longer life.
Shares OptimICE-pCR (A012103), KEYNOTE-522, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Pembrolizumab and the tag tnbc-evidence.
Shares SCARLET (SWOG S2212), Anthracyclines (doxorubicin, epirubicin), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Doxorubicin and the tag tnbc-evidence.
Shares De-escalation, escalation and response-adapted therapy, KEYNOTE-522, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Pembrolizumab and the tag tnbc-evidence.
Shares Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis, Pathologic complete response (pCR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares KEYNOTE-522, Pathologic complete response (pCR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Doxorubicin and the tag tnbc-evidence.
Shares Anthracyclines (doxorubicin, epirubicin), Pathologic complete response (pCR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Tumour-infiltrating lymphocytes (TILs), Pathologic complete response (pCR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Trial design, endpoints and cost, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Pembrolizumab, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.