Loading
When triple-negative breast cancer is still present at surgery after pre-operative chemotherapy and pembrolizumab, the amount left (the residual cancer burden) is what decides the next treatment: a year of olaparib for inherited BRCA carriers, capecitabine for others, pembrolizumab to complete the year, and trials of antibody-drug conjugates for everyone else.
About a third of patients treated on the KEYNOTE-522 regimen have residual invasive disease at surgery (pathological complete response 64.8 percent with pembrolizumab versus 51.2 percent without, first 602 patients). Residual cancer burden (RCB) grades what is left: in a pooled analysis of 5,161 patients across 12 cohorts, each unit of the continuous RCB score raised the hazard of an event-free survival event, and RCB class was prognostic in every subtype including triple-negative disease. In KEYNOTE-522 pembrolizumab shifted patients to lower RCB classes and cut events within RCB-0, RCB-1 and RCB-2 (hazard ratios 0.70, 0.92 and 0.52) but not RCB-3 (1.24); among RCB-0/1 patients more than half of events were central nervous system recurrences.
What the trials say about treatment after residual disease: capecitabine for six to eight cycles improved five-year disease-free survival from 56.1 to 69.8 percent and overall survival from 70.3 to 78.8 percent in the triple-negative subgroup of CREATE-X (Japan and Korea, no immunotherapy era); one year of olaparib improved three-year invasive disease-free survival from 77.1 to 85.9 percent and overall survival (hazard ratio 0.68 at the second interim analysis) in germline BRCA carriers in OlympiA, 82 percent of whom had triple-negative disease; platinum was not better than capecitabine in EA1131 (stopped for futility); genomically directed therapy was not better than physician's choice in BRE12-158; and adjuvant pembrolizumab continues to complete a year in the KEYNOTE-522 pathway, with its independent contribution untested (SWOG S1418 will report it). The open randomised trials for this group are ASCENT-05/OptimICE-RD (sacituzumab govitecan with pembrolizumab, 10 UK sites) and TROPION-Breast03 (datopotamab deruxtecan with or without durvalumab, 12 UK sites), both with invasive disease-free survival as the primary endpoint. ctDNA after surgery marks the highest-risk group: in the UK c-TRAK TN trial 27 percent of patients had ctDNA detected within 12 months and 72 percent of those already had metastases on scans when it was found, so testing has to start earlier and be more sensitive before it can steer treatment.
Showing the molecule this term concerns: Capecitabine.
Shares TROPION-Breast03, ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63), Residual cancer burden (RCB), KEYNOTE-522.
Shares TROPION-Breast03, ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63), Residual cancer burden (RCB), KEYNOTE-522.
Shares OlympiA, Residual cancer burden (RCB), KEYNOTE-522, Pathologic complete response (pCR).
Shares PHOENIX DDR/Anti-PD-L1, Germline BRCA mutation (gBRCA), KEYNOTE-522, Pathologic complete response (pCR).
Shares SWOG S1418 / NRG BR006, Residual cancer burden (RCB), Event-free / disease-free survival (EFS, DFS, iDFS, RFS), KEYNOTE-522.
Shares De-escalation, escalation and response-adapted therapy, Residual cancer burden (RCB), KEYNOTE-522, Pathologic complete response (pCR).
Shares TROPION-Breast03, ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63), Residual cancer burden (RCB), Pathologic complete response (pCR).
Shares Residual cancer burden (RCB), Event-free / disease-free survival (EFS, DFS, iDFS, RFS), KEYNOTE-522, Pathologic complete response (pCR).