“The combination of neratinib (Nerlynx) and T-DM1 (ado-trastuzumab emtansine; Kadcyla) induced an overall response rate of 60% in previously-treated women with HER2-positive metastatic breast cancer, according to results from the phase Ib NSABP FB-10 study presented at the 2018 ASCO Annual Meeting.
“Among 12 of 20 evaluable patients with objective responses, 3 had a complete response and 9 had a partial response. An additional 2 patients had stable disease, and 6 patients had progressive disease.”
“Tucatinib used in combination with capecitabine, trastuzumab (Herceptin), or both agents showed promising antitumor activity in heavily pretreated women with HER2-positive breast cancer with or without brain metastases, according to findings published in The Lancet Oncology.
“In phase Ib results from a nonrandomized, open-label study, 83% (5/6) of patients with measurable disease treated with tucatinib/capecitabine had an objective response, as did 40% (6/15) of patients receiving tucatinib/trastuzumab. Sixty-one percent (14/23) of patients treated with the combination of all 3 drugs had an objective response.”
“A combined approach targeting estrogen receptor (ER), HER2, and RB1 yielded promising results in terms of Ki-67 expression in an exploratory study of women with HER2-positive, ER-positive breast cancer.
” ‘HER2-positive, ER-positive tumors have molecular features distinct from those of HER2-positive, ER-negative cancers, suggesting that the two types of tumors should be treated with differently tailored approaches,’ wrote study authors led by Luca Gianni, MD, of San Raffaele Scientific Institute in Milan. Previous work has suggested that a combined approach targeting HER2, ER, and RB1 may improve outcomes.”
Diagnosis of adenocarcinoma of the lung, a major subtype of non-small lung cancer (NSCLC), nowadays triggers mandatory testing of tumor tissue for alterations in four genes: EGFR, ALK, ROS1, and more recently, BRAF. If present, these alterations predict sensitivity to specific targeted drugs approved by the U.S. Food and Drug Administration (FDA) that work better and often longer than standard chemotherapy, and are better tolerated.
However, there are many more targetable/actionable genomic alterations (also known as “drivers”) in NSCLC. This blog post will briefly discuss most of them, with the goal of promoting molecular testing for more than the four “usual suspects” mentioned above. Some patients with these alterations may benefit from FDA-approved drugs or from enrollment in clinical trials that are testing additional drugs and drug combinations. Continue reading…
“The adjuvant treatment landscape for patients with HER2-positive breast cancer continues to grow, particularly following the recent FDA approval of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and chemotherapy, which was based on findings from the APHINITY trial.
“In the phase III trial, the combination demonstrated a 3-year invasive disease-free survival (DFS) rate of 94.1%, which represented an 18% reduction in the risk of developing invasive disease or death. The benefit was more pronounced among higher-risk patients. The DFS rate for patients with node-positive disease was 92.0% with pertuzumab versus 90.2% with standard therapy.”
“A combination of pembrolizumab (Keytruda) and trastuzumab, tested in patients with trastuzumab-resistant advanced HER2-positive breast cancer, was well tolerated and had clinical benefit in patients whose tumors were positive for a biomarker for pembrolizumab, according to data presented from the phase Ib/II PANACEA trial at the 2017 San Antonio Breast Cancer Symposium, held Dec. 5–9.
“ ‘We wanted to investigate if immunotherapy approaches can work in patients with advanced HER2-positive breast cancer that is resistant to trastuzumab,’ said Sherene Loi, MD, PhD, associate professor at Peter MacCallum Cancer Centre in Melbourne, Australia, working with the International Breast Cancer Study Group (IBCSG).”
“Traditional neoadjuvant chemotherapy along with dual HER2-targeted blockade yielded significantly better response rates than a novel approach using HER2-targeted chemotherapy plus HER2-targeted blockade, according to a randomized phase III trial.
” ‘Despite the improvements in outcomes associated with HER2-directed therapy, approximately a quarter of patients who receive treatment for their early breast cancer remain at risk of relapse after 8–10 years, and around 15% will die within a decade,’ wrote study authors led by Sara A. Hurvitz, MD, of the David Geffen School of Medicine at the University of California, Los Angeles. A need for new strategies in this setting led the investigators to test a neoadjuvant regimen of the antibody–drug conjugate trastuzumab emtansine along with pertuzumab in comparison with traditional systemic chemotherapy along with trastuzumab plus pertuzumab.”
“A new randomized trial found that neoadjuvant trastuzumab/pertuzumab alone yields a substantially worse rate of pathologic complete response compared with trastuzumab/pertuzumab plus paclitaxel in women with early, HER2-positive, hormone receptor (HR)-negative breast cancer.
” ‘Pathologic complete response (pCR) after neoadjuvant [therapy] has strong prognostic impact in HER2 disease,’ wrote study authors led by Ulrike Nitz, MD, of the West German Study Group GmbH in Moenchengladbach, Germany. The WSG-ADAPT HER2+/HR− trial assessed whether dual blockade with trastuzumab and pertuzumab could achieve similar rates of pCR in those with strong early response to dual blockade along with chemotherapy.”