Dose-dense anthracycline-taxane chemotherapy (CTx) is standard for high-risk early breast cancer (eBC) and is often given in the neoadjuvant setting if CTx is clearly indicated (e.g., recurrence score, RS > 25 and/or > 4 positive lymph nodes by imaging) or if downstaging is needed. While dose-dense CTx improves outcomes irrespective of hormone receptor (HR) status in meta-analyses, its benefit in node-negative HR+ eBC appears limited. Further meta-analyses on neoadjuvant vs adjuvant use, and on mono- vs combined therapy, showed mixed results. These findings highlight an unmet need for a refined treatment selection, informed by the assessment of relative survival benefit. We therefore pooled the WSG ADAPT-HR+/HER2- and PlanB trials to estimate the impact of dose density, anthracycline use, and treatment setting on survival.
Invasive (iDFS), distant disease-free survival (dDFS), and overall survival (OS) were analyzed retrospectively in a pooled analysis of HR+/HER2- patients (pts) in ADAPT-HR+/HER2- (n = 2331) and PlanB (n = 2220) who received chemotherapy and had follow-up data (data cut: Jan 26, 2026). In ADAPT-HR+/HER2-, pts high-risk received 8× weekly nab-paclitaxel vs. 4× biweekly sb-paclitaxel, followed by epirubicin + cyclophosphamide (EC) in either the neoadjuvant or adjuvant setting. PlanB randomized pts intermediate- to high-risk to adjuvant 4× EC followed by 4× docetaxel (EC-T) vs. 6× TC. To minimize bias, predefined uniform cross-trial subgroups (RS > 25 any pN; pN2–3 any RS) were considered here, and propensity scoring for non-random allocations (neoadjuvant vs adjuvant CTx in ADAPT-HR+/HER2-, physician choice).
This pooled analysis included 1467 pts with RS > 25 and 551 with clinically (neoadjuvant cohort in ADAPT-HR+/HER2-) or pathologically N2-3 eBC. Dose-dense anthracycline or paclitaxel yielded inferior iDFS and dDFS than q3w docetaxel, even after adjustment for cT, age, and grade. This effect, favoring a (longer) docetaxel-based CTx, was present among N2-3 pts with RS ≤25, who showed better iDFS, dDFS, and OS, and among RS > 25 pts (in particular, in N0-1), who showed better dDFS. Informed by these results, we assessed the impact of anthracyclines in PlanB pts with RS > 25 and/or N2-3 and observed no significant survival differences. There was no significant survival difference between neoadjuvant vs adjuvant CTx in the corresponding subset of ADAPT-HR+/HER2- pts, even in propensity-scored analysis.
Our exploratory retrospective analysis does not show a significant survival difference by anthracycline use or treatment setting (neoadjuvant vs adjuvant) in high-risk HR+/HER2- eBC pts who are candidates for CTx. Optimal use of dose-dense CTx in the context of docetaxel-based treatment requires further investigation.
NCT01779206; NCT01049425. This is an ASCO Meeting Abstract from the 2026 ASCO Annual Meeting II. This abstract does not include a full text component.
Progression-free survival (PFS) was statistically significantly improved with addition of tucatinib versus placebo 24.9 v 16.3 months regardless of the presence/absence of BM or hormone receptor status.
Primary objective not met, ctDNA clearance post- neoadjuvant therapy (NAT) cannot reliably predict pathologic complete response (pCR) and shouldn't be used to defer surgery. But the prognostic data are striking: post-NAT ctDNA positivity independently predicted recurrence in triple-negative breast cancer (TNBC) (HR 8.9), and the postsurgical landmark analysis is essentially binary, 100% of ctDNA-positive patients recurred while 94% of ctDNA-negative patients were disease-free at 5 years (HR 128). Not practice-changing yet pending prospective utility trials, but this strongly validates ultrasensitive ctDNA as a prognostic tool and a smart enrollment biomarker for future escalation/de-escalation trials.
Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway. PFS was 9.3 m in the gedatolisib-triplet group vs 2.0 m in the fulvestrant group (hazard ratio) HR 0.24, and 7.4 m in the gedatolisib-doublet group HR 0.33 v fulvestrant.
This is impressive. However, there is no reported placebo trastuzumab deruxtecan arm, so this is not truly a “no chemotherapy” regimen. It is important to remember that deruxtecan is itself a chemotherapy agent. So, this is really comparing deruxtecan vs taxol or more accurately, a comparison of chemotherapy delivery systems.
The QUIWI study used quizartinib, a FLT3 drug added to standard chemo induction/consolidation in FLT-negative acute myeloid leukemia (AML) patients. There was a meaningful overall survival (OS) improvement across all age and risk groups including the NPM1+ population. They purposefully used a higher dose to achieve what is felt to be off-target TKI activity in familiar pathways of KIT, PDGRF…etc.