DD adjuvant CT improves disease free survival (DFS) and overall survival (OS) in high-risk, hormone receptor positive BC. Luminal A and luminal B subtypes have different sensitivity to (neo)adjuvant chemotherapy; however, their role in predicting DD efficacy in clinically high-risk setting is uncertain. This exploratory analysis of the GIM2 trial (Del Mastro et al, Lancet 2015) evaluated DD efficacy according to IHC defined luminal subtypes.
In the GIM2 trial, pts with node-positive early BC were randomized to receive 4 cycles of (fluorouracil) epirubicin/cyclophosphamide every 2 (DD) or every 3 (standard interval [SI]) weeks followed by 4 cycles of DD or SI paclitaxel. Luminal A-like and luminal B-like BC were identified according to 13h St Gallen definition as having a Ki67<20% and a PgR>/=20% (luminal A-like), and a Ki67>/=20% and/or a PgR<20% (luminal B-like). Pts with HER2-positive BC were excluded. The efficacy of DD CT in terms of DFS and OS was compared between the two subtypes.
Of 2,003 pts enrolled in the GIM2 trial, 401 had luminal A-like and 657 luminal B-like BC. After a median follow-up of 8 years, DFS was 81.1% (95% Confidence Intervals [CI] 76.6-84.7) and 70.6% (66.6-74.1) in luminal A-like and B-like BC, respectively; OS was 91.6% (88.1-94.1) and 85% (81.7-87.7), respectively. There was no significant interaction between treatment and luminal subtypes (pinteraction=0.416 for DFS and pinteraction=0.313 for OS); however, the effect of DD CT appeared to be greater in luminal-B like BC (see table below). 186P8 year DFS SI 8 year DFS DD HR (95% CI) luminal A-like 81.6 80.6 0.86 (0.56-1.30) luminal B-like 66.8 74.7 0.74 (0.55-0.98) 8 year OS SI 8 year OS DD Luminal A-like 92.9 90.6 0.88 (0.47-1.67) luminal B-like 80.8 89.4 0.61 (0.40-0.93)
These long-term results confirm the prognostic value of IHC-defined luminal subtypes, with luminal B-like bearing a worse prognosis. In clinically high-risk, hormone receptor positive BC, luminal B-like subtype benefits more from DD CT both in terms of DFS and OS.
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M. Lambertini: Honoraria (self), speaker honoraria: Theramex; Advisory / Consultancy: Teva. M. De Laurentiis: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Celgene. S. De Placido: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Eisai; Honoraria (self): Novartis; Honoraria (self): Celgene; Honoraria (self): Eli Lilly. F. Montemurro: Honoraria (self), speaker honoraria: AstraZeneca; Honoraria (self), speaker honoraria: Pfizer; Honoraria (self), speaker honoraria: Novartis; Honoraria (self), speaker honoraria: Eli Lilly; Honoraria (self), Travel / Accommodation / Expenses, speaker honoraria, travel grant: Roche. L. Del Mastro: Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Ipsen; Honoraria (self): Roche-Genentech; Honoraria (self): Takeda; Honoraria (self): Eli Lilly. All other authors have declared no conflicts of interest.