TY - JOUR
T1 - Adjuvant Anti-HER2 Therapy, treatment-related amenorrhea, and survival in premenopausal HER2-positive early breast cancer patients
AU - Lambertini, Matteo
AU - Campbell, Christine
AU - Bines, José
AU - Korde, Larissa A.
AU - Izquierdo, Miguel
AU - Fumagalli, Debora
AU - Del Mastro, Lucia
AU - Ignatiadis, Michail
AU - Pritchard, Kathleen
AU - Wolff, Antonio C.
AU - Jackisch, Christian
AU - Lang, Istvan
AU - Untch, Michael
AU - Smith, Ian
AU - Boyle, Frances
AU - Xu, Binghe
AU - Barrios, Carlos H.
AU - Baselga, José
AU - Moreno-Aspitia, Alvaro
AU - Piccart, Martine
AU - Gelber, Richard D.
AU - De Azambuja, Evandro
N1 - Funding Information:
The ALTTO trial received financial support from GlaxoSmithKline (until January 2015), Novartis Pharma AG (as of January 2015), and the National Cancer Institute of the National Institutes of Health (Grant No. U10CA180821 and U10CA180882 to the Alliance for Clinical Trials in Oncology and Grant No. CA025224 to the legacy North Central Cancer Treatment Group). The present analysis did not receive additional funding.
Funding Information:
Matteo Lambertini acknowledges support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at Institut Jules Bordet in Brussels (Belgium).
Funding Information:
Matteo Lambertini served as a consultant for Teva and received a travel grant from Astellas outside the submitted work. Miguel Izquierdo reports employment at Novartis Pharma AG. Lucia Del Mastro received personal fees from Novartis Pharma AG, Roche-Genentech, Ipsen, Astrazeneca, Takeda, and Eli Lilly outside the submitted work. Michail Ignatiadis served as a consultant for Roche-Genentech and received a research grant from Roche-Genentech (to the insitution) outside the submitted work. Martine Piccart received honoraria from Novartis Pharma AG and Roche-Genentech and a research grant from Novartis Pharma AG and Roche-Genentech (to the insitution). Richard D. Gelber received a research grant from Novartis Pharma AG and Roche-Genentech (to institution). Evandro de Azambuja received honoraria from Roche-Genentech, a research grant from Roche–Genentech (to the insitution), and travel grants from Roche-Genentech and GlaxoSmithKline outside the submitted work. Jose Baselga reports non-financial support from Roche/ Genentech, during the conduct of the study; personal fees and other from Aura Biosciences, personal fees and other from Northern Biologics (f/k/a Mosaic Biomedicals), personal fees and other from Infinity Pharmaceuticals, other from ApoGen Biotechnologies, personal fees and other from PMV Pharma, personal fees and other from Juno Therapeutics, personal fees and other from TANGO (f/k/a Synthetic Lethal), personal fees and other from Grail, personal fees and other from Varian Medical Systems, other from Foghorn Therapeutics, personal fees and non-financial support from Novartis, personal fees and non-financial support from Eli Lilly, personal fees and other from Bristol Myers Squibb, personal fees and other from Venthera, personal fees and other from Seragon, outside the submitted work. All remaining authors have declared no conflicts of interest.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Background In premenopausal patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, the gonadotoxicity of trastuzumab and lapatinib remains largely uncertain, and the prognostic effect of treatment-related amenorrhea (TRA) is unknown. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase III trial, HER2-positive early breast cancer patients were randomized (1:1:1:1) to receive one year of trastuzumab, lapatinib, their sequence, or their combination. As per study protocol, menopausal status was collected in all patients at random assignment and at week 37 visit. We investigated TRA rates and whether TRA in patients with hormone receptor-positive and -negative tumors would impact disease-free survival (DFS) and overall survival (OS). Landmark and time-dependent modeling were used to account for guarantee-time bias. All statistical tests were two-sided. Results A total of 2862 premenopausal women were included, of whom 1679 (58.7%) had hormone receptor-positive disease. Median age was 43 (interquartile range = 38-47) years. Similar TRA rates were observed in the trastuzumab (72.6%), lapatinib (74.0%), trastuzumab → lapatinib (72.1%), and trastuzumab+lapatinib (74.8%) arms (P =.64). The association between TRA and survival outcomes differed according to hormone-receptor status (P interaction for DFS =.007; P interaction for OS =.003). For hormone receptor-positive patients, the TRA cohort had statistically significantly better DFS (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.45 to 0.76) and OS (aHR = 0.63, 95% CI = 0.40 to 0.99) than the no TRA cohort. No difference was observed in hormone receptor-negative patients. Conclusions In this unplanned analysis, no association between TRA rate and type of anti-HER2 treatment was observed. TRA was associated with statistically significant survival benefits in premenopausal hormone receptor-positive/HER2-positive early breast cancer patients.
AB - Background In premenopausal patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, the gonadotoxicity of trastuzumab and lapatinib remains largely uncertain, and the prognostic effect of treatment-related amenorrhea (TRA) is unknown. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase III trial, HER2-positive early breast cancer patients were randomized (1:1:1:1) to receive one year of trastuzumab, lapatinib, their sequence, or their combination. As per study protocol, menopausal status was collected in all patients at random assignment and at week 37 visit. We investigated TRA rates and whether TRA in patients with hormone receptor-positive and -negative tumors would impact disease-free survival (DFS) and overall survival (OS). Landmark and time-dependent modeling were used to account for guarantee-time bias. All statistical tests were two-sided. Results A total of 2862 premenopausal women were included, of whom 1679 (58.7%) had hormone receptor-positive disease. Median age was 43 (interquartile range = 38-47) years. Similar TRA rates were observed in the trastuzumab (72.6%), lapatinib (74.0%), trastuzumab → lapatinib (72.1%), and trastuzumab+lapatinib (74.8%) arms (P =.64). The association between TRA and survival outcomes differed according to hormone-receptor status (P interaction for DFS =.007; P interaction for OS =.003). For hormone receptor-positive patients, the TRA cohort had statistically significantly better DFS (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.45 to 0.76) and OS (aHR = 0.63, 95% CI = 0.40 to 0.99) than the no TRA cohort. No difference was observed in hormone receptor-negative patients. Conclusions In this unplanned analysis, no association between TRA rate and type of anti-HER2 treatment was observed. TRA was associated with statistically significant survival benefits in premenopausal hormone receptor-positive/HER2-positive early breast cancer patients.
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U2 - 10.1093/jnci/djy094
DO - 10.1093/jnci/djy094
M3 - Article
C2 - 29878225
AN - SCOPUS:85059873068
VL - 111
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 1
M1 - djy094
ER -