Neoadjuvant Dabrafenib/Trametinib Leads to High pCR Rates in Bulky Resectable Melanoma, But Recurrences Are Common

Excerpt:

“Phase II results demonstrated that nearly half of patients with resectable stage IIIB/C BRAF V600-mutant melanoma achieved pathologic complete response (pCR) with neoadjuvant combination therapy consisting of dabrafenib (Tafinlar) and trametinib (Mekinist). Additionally, no patients experienced disease progression during the neoadjuvant treatment, said Alexander M. Menzies, MD, who presented the data at the 2017 ESMO Congress in Madrid.

” ‘Nearly 50% of our patients had a complete eradication of their melanoma at the time of surgery. Fifty percent had some remaining melanoma in the surgical specimen, but every patient had some degree of tumor shrinkage on therapy,’ said Menzies, a medical oncologist and senior research fellow at Melanoma Institute Australia in Sydney, Australia. ‘These are patients who otherwise would just have surgery and then have observation. And, these are patients who are at very high risk, probably the highest risk of recurrence without further therapy.’ ”

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Neoadjuvant T-DM1/Pertuzumab Combo Boosts pCR in HER2+ Breast Cancer

Excerpt:

“Neoadjuvant ado-trastuzumab emtansine (T-DM1; Kadcyla) in combination with pertuzumab (Perjeta) improved pathologic complete response (pCR) compared with standard of care in patients with advanced HER2-positive breast cancer, according to recently reported data from the adaptively randomized I-SPY 2 trial.

“Of the 249 patients with HER2-positive disease included in the I-SPY 2 trial, 54% of those who received T-DM1/pertuzumab experienced a pCR compared with 22% of those who received the combination of paclitaxel (Abraxane) plus trastuzumab (Herceptin).

“These findings suggest that T-DM1 may ultimately increase survival in these patients, says lead study author Angela M. DeMichele, MD, professor of Medicine and Epidemiology at the University of Pennsylvania.”

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Neoadjuvant T-DM1 Shows Promising pCR Rates in HER2+/HR+ Early Breast Cancer

“Chemotherapy-free neoadjuvant treatment with trastuzumab emtansine (T-DM1; Kadcyla) demonstrated a pathological complete response (pCR) rate of 40.5% in patients with HER2+ and HR+ early breast cancer, according to findings from the phase II ADAPT trial presented at the 2015 ASCO Annual Meeting.

” ‘After 12 weeks without systemic chemotherapies we observed more than a 40% pCR in both the breast and nodes in our T-DM1-treated HER+/HR+ patients,’ said lead investigator Nadia Harbeck, MD, PhD, head of the Breast Center, Oncological Therapy and Clinical Trials Unit, University of Munich, Germany. ‘We did see very low overall toxicity, and did not detect any new safety signals.’

“The ADAPT trial is a large umbrella trial that has enrolled 5000 patients with various breast cancer phenotypes. In the arm of the trial presented at ASCO, 376 patients with HER2+ and HR+ breast cancer were randomized to receive neoadjuvant T-DM1 at 3.6 mg/kg with or without endocrine therapy or trastuzumab plus endocrine therapy. Treatment was administered for 4 cycles followed by surgery and 1-year of standard adjuvant chemotherapy plus trastuzumab.”


The Role of Pertuzumab in Treating HER2+ Breast Cancer


Pertuzumab (Perjeta) is a relatively new drug that targets HER2, a protein found at higher-than-normal levels in about 15% to 20% of all breast cancers. Too much HER2 leads to tumor growth. Currently, all newly diagnosed breast cancer patients have their tumors’ HER2 levels tested. Knowing whether a patient’s HER2 levels are abnormally high (HER2-positive) or normal (HER2-negative) is a major factor in choosing a treatment, thanks to the availability of trastuzumab (Herceptin) and, now, other HER2-targeted drugs such as Perjeta, T-DM1 (Kadcyla), and lapatinib (Tykerb). These drugs are all used to treat HER2-positive patients. Continue reading…


Longer Neoadjuvant Anti-HER2 Treatment Might Be More Effective for HER2+ Patients

The gist: Stage II and III breast cancer patients whose tumors are HER2-positive may benefit from longer treatment with the anti-HER2 drugs trastuzumab (aka Herceptin) and lapatinib (Tykerb). In a clinical trial, 28% of patients who received the drugs for 24 weeks had no more signs of an invasive tumor after their treatment. Only 12% of patients who received the drugs for 12 weeks had the same result. However, the difference in response was significant only in patients whose tumors were hormone receptor (HR)-positive and HER2-positive.