The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease.
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Hunter Natasha B, Parsons Heather A, Cope Leslie, Canzoniero Jenna V, Navarro Fabio C P, El-Refai Sherif, Anampa Jesus D, Sparano Joseph A, Rimawi Mothaffar, Storniolo Anna Maria, Mainor Candace, Nanda Rita, DeMichele Angela, Gupta Gaorav P, Stringer-Reasor Erica J, Lynce Filipa, Cobain Erin F, Puhalla Shannon, Jankowitz Rachel, Rexer Brent, Mayer Ingrid, Hwang E Shelley, Blackwell Kimberly, El Ayass Walid, Lee Young, Tweed Carol, Wilkinson Mary, Pennisi Angela, Sun Bonnie, Wright Pamela, Gralow Julie R, Chen Richard, Boyle Sean M, Stearns Vered, Wolff Antonio C, Park Ben Ho
Аннотация
METHODS: Pathologic Response Evaluation and Detection in Circulating Tumor-DNA is a prospective, multicenter study evaluating ctDNA as a biomarker of treatment response using a tumor-informed, ultrasensitive (<100 parts per million) assay. The primary objective was to determine whether the negative predictive value (NPV) of post-NAT ctDNA for pCR was ≥90%. A prespecified secondary objective for the TNBC cohort was to assess associations between ctDNA and 5-year invasive disease-free survival (IDFS). ctDNA was evaluated at baseline, after NAT before surgery, and after surgery.
RESULTS: Of 227 enrolled patients, 220 were evaluable for pCR (48% HER2-positive; 52% TNBC) and 91 patients (41%) had pCR. The primary objective was not met. Although all patients with pCR were ctDNA-negative after NAT, 40% of non-pCR patients were also ctDNA-negative (NPV, 60% [95% CI, 0.50 to 0.69]). However, the prespecified secondary objective was met. Detectable ctDNA after NAT was prognostic for recurrence (hazard ratio [HR], 8.9 [95% CI, 2.4 to 33]; P = .001), independent of pCR. Additionally, detectable ctDNA after surgery identified patients at extremely high recurrence risk (HR, 128 [95% CI, 15 to 1,083]; P < .001), while ctDNA-negative patients after surgery had 94% 5-year IDFS.
CONCLUSION: In HER2-positive breast cancer and TNBC, ctDNA after NAT does not discriminate pCR from non-pCR. However, ctDNA provides markedly superior prognostic stratification, identifying patients with exceptional outcomes and those at extreme risk. These findings support ctDNA-guided therapeutic de-escalation and escalation strategies.