“In the phase III BOLERO-1 trial, reported in The Lancet Oncology, Hurvitz et al found that the addition of the mTOR inhibitor everolimus (Afinitor) to trastuzumab (Herceptin)-paclitaxel did not significantly increase progression-free survival among patients with HER2-positive advanced breast cancer. A 7-month prolongation in progression-free survival was observed with everolimus among patients with hormone receptor–negative disease.”
“Results from a phase II trial showed that neoadjuvant TDM-1 is effective in treating HER2-positive, hormone receptor (HR)-positive breast cancer, with or without endocrine therapy, in comparison with trastuzumab and endocrine therapy. Results of the study (abstract 506) were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.
“The WSG-ADAPT trial is an umbrella trial that included around 5,000 patients. This sub-study of that trial included patients with HER2-positive, HR-positive early breast cancer; it enrolled 376 patients at 48 sites, and this interim analysis included 130 of those patients. The trial has been closed early because efficacy was reached.
“The patients were randomized to receive either TDM-1 monotherapy (37 patients), TDM-1 with endocrine therapy (48 patients), or trastuzumab with endocrine therapy (45 patients). ‘This was not a low-risk population,’ said study presenter Nadia Harbeck, MD, PhD, of the University of Munich, noting that over half of the patients were premenopausal and about half had tumors that were larger than 2 cm.”
“Breast cancer patients received suboptimal cardiac monitoring during treatment with trastuzumab (Herceptin), according to a large population-based study.
“Among more than 2,000 patients, only 36% of evaluable participants received adequate monitoring for cardiotoxicity in accordance with current guidelines, reported Mariana Chavez-MacGregor, MD, of the MD Anderson Cancer Center in Houston, and colleagues.
“Interestingly, physician characteristics had more influence than patient factors on cardiac monitoring, they wrote in the Journal of Clinical Oncology
” ‘We suspected that the rates of cardiac monitoring were going to be low, but we were surprised on how low, particularly in this high-risk group of patients,’ Chavez-MacGregor, a medical oncologist, told MedPage Today in a separate interview. ‘Of particular concern was that even among patients with cardiac comorbidities the rates of cardiac monitoring were not higher.’ “
“On May 16, 2005, at about 1:30 p.m. local time, I was one of several hundred fortunate persons crowded into a conference hall at the ASCO Annual Meeting when the wide separation of the DFS curves in the joint analysis of NCCTG 9831 and NSABP B-31 was first shown.
“The benefit of adjuvant trastuzumab was dramatic, and the results changed clinical practice that very next Monday morning.
“Because there was a known cardiac risk of trastuzumab, patients with smaller lymph node-negative breast cancers either were excluded or underrepresented in the initial adjuvant trastuzumab studies, thus making extrapolation of these impressive results somewhat problematic for patients at lower risk for invasive recurrence.”
“In HER2-positive breast cancer, lapatinib (Tykerb) combined with a taxane was linked to shorter progression-free survival (PFS) and more toxicity compared with trastuzumab (Herceptin) plus a taxane, according to results from an international trial.
“In the National Cancer Institute of Canada (NCIC) Clinical Trials Group (CTG) MA.31 study, the median intention-to-treat (ITT) PFS was 9.0 months with lapatinib versus 11.3 months with trastuzumab when paired with a taxane, according to Karen A. Gelmon, MD, of the British Columbia Cancer Agency in Vancouver, and colleagues.
“In addition, lapatinib plus a taxane was associated with more toxicity in patients with centrally confirmed HER2-positive tumors, and overall survival (OS) was worse in the confirmed HER2-positive group treated with lapatinib (ITT hazard ratio 1.28, 95% CI 0.95-1.72, P=0.11), they wrote in the Journal of Clinical Oncology.
” ‘Our results support the use of trastuzumab over lapatinib in the HER2 treatment-naive first-line metastatic setting,’ Gelmon’s group stated. ‘The NCIC CTG MA.31 trial was the first head-to-head comparison to our knowledge of trastuzumab and lapatinib in locally determined metastatic HER2-positive breast cancer, with separate analysis for centrally determined HER2 disease.’ “