The gist: A recent clinical trial tested a new breast cancer treatment in volunteer patients. The treatment combines a new drug called neratinib with the chemotherapy drug capecitabine. The trial found promising results for patients who had HER2-positive metastatic breast cancer and who had already been treated with trastuzumab (Herceptin) and taxanes. Some of the patients had also had prior treatment with the drug lapatinib (Tykerb). Patients interested in this treatment can now enroll in a new phase III clinical trial.
“Neratinib is an irreversible pan-tyrosine kinase inhibitor with activity against HER1, HER2, and HER4. In a phase I/II trial reported in the Journal of Clinical Oncology, Saura et al found that the combination of neratinib and capecitabine exhibited high activity in patients with trastuzumab (Herceptin)- and taxane-pretreated HER2-positive metastatic breast cancer, including those with prior treatment with the dual HER1/HER2 kinase inhibitor lapatinib (Tykerb)…
“In the phase I dose-escalation phase in 33 patients, the maximum tolerated dose of the combined regimen was found to be neratinib at 240 mg once a day continuously and capecitabine at 1,500 mg/m2 twice a day on days 1 and 14 every 21 days. No dose-limiting toxicity was observed at this level; dose-limiting toxicities at higher doses of neratinib or capecitabine included diarrhea, increased liver enzymes, and asthenia…
“In the phase II portion, 72 patients, including 7 with prior lapatinib treatment, received the maximum tolerated dose of the combination. The overall response rate in 65 patients with no prior lapatinib was 64% (95% confidence interval [CI] = 51%–76%), including complete response in 12%. In the 7 patients with prior lapatinib treatment, the response rate was 57% (95% CI = 18%–90%), including complete response in 1 patient (14%).
“Stable disease ≥ 24 weeks was achieved in an additional 8% and 14% of patients. Median progression-free survival was 40.3 weeks (95% CI = 30.3–66.0 weeks) and 35.9 weeks (95% CI = 18.9–60.1 weeks).”
The gist: Drug company giant Roche is mixing drugs in new combinations to provide melanoma and breast cancer patients with potential new treatments. This article outlines the company’s endeavors.
“Mixing drugs in various combinations has given Roche Holding AG (ROG) effective new treatments for skin and breast cancer strains.
“Combining Zelboraf, a melanoma drug now on the market, with experimental cobimetinib showed significant improvement over Zelboraf alone, according to data presented today at the European Society for Medical Oncology’s annual meeting in Madrid.
“Roche said yesterday that a combination of two breast cancer drugs, plus chemotherapy, could add almost 16 months to the lives of a class of patients. Roche today also reported data from an early-stage study of its MPDL3280A immune therapy treatment in bladder cancer which showed a 52 percent response rate. If successfully developed, the drug will be the first new treatment for bladder cancer in 30 years, the Basel, Switzerland-based company said.
“ ‘This is a good meeting for Roche,’ said Asthika Goonewardene, an analyst with Bloomberg Intelligence. ‘They’re firing in three different areas.'”
“Analysis of more than 8,000 women who participated in the world’s largest study of two treatments for HER2-positive breast cancer reinforces other findings from the clinical trial showing that trastuzumab (Herceptin) should remain the standard of care for this cancer, says a Mayo Clinic researcher.
“This study, being presented at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, reveals that when used as a single HER2-targeted therapy in addition to standard chemotherapy, trastuzumab offers a better outcome than does lapatinib (Tykerb), says Edith A. Perez, M.D., deputy director at large, Mayo Clinic Cancer Center and director of the Breast Cancer Translational Genomics Program at Mayo Clinic in Florida.
“Dr. Perez is co-chair of ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization study). The phase III clinical trial, which tested combinations of the two drugs or use of the drugs by themselves—in addition to standard chemotherapy—enrolled 8,381 participants at 946 medical centers in 44 countries.
“A key finding from ALTTO, released in June, showed that lapatinib, when used in addition to trastuzumab as part of dual therapy, did not offer any statistically significant benefit to patients, such as disease-free survival or overall survival. Dual blockade using two anti-HER2 drugs only increased toxicity, said Dr. Perez.”
“A drug used to treat advanced breast cancer has had what appears to be unprecedented success in prolonging lives in a clinical trial, researchers reported on Sunday.
“Patients who received the drug — Perjeta, from the Swiss drug maker Roche — had a median survival time nearly 16 months longer than those in the control group.
“That is the longest amount of time for a drug used as an initial treatment for metastatic breast cancer, the researchers said, and it may be one of the longest for the treatment of any cancer.
“Most cancer drugs prolong survival in patients with metastatic disease for a few months at most. Metastasis means the cancer has spread to other parts of the body.
“ ‘We’ve never seen anything like this before,’ said Dr. Sandra M. Swain of the MedStar Washington Hospital Center in Washington, the lead author of the study. ‘It’s really unprecedented to have this survival benefit.’ ”
The gist: Researchers recently tested a breast cancer treatment in a clinical trial—a research study with volunteer patients. The treatment combines the drug trastuzumab (aka Herceptin) with a new drug called eribulin mesylate. The goal of the trial was to find out how well the combination might work for patients who had already been treated with trastuzumab. All patients who participated had HER-positive metastatic breast cancer. It was found that the treatment was safe and effective, regardless of whether patients had already taken trastuzumab.
“Eribulin mesylate plus trastuzumab demonstrated activity in patients with HER-2–positive metastatic breast cancer regardless of prior treatment with trastuzumab, according to phase 2 study results presented at the Breast Cancer Symposium.
“Joyce O’Shaughnessy, MD, of the Texas Oncology Baylor Charles A. Sammons Cancer Center, and colleagues sought to evaluate whether prior trastuzumab (Herceptin, Genentech) affected the efficacy of eribulin mesylate (Halaven, Eisai) plus trastuzumab. Previous data indicated the combination conferred a 71% objective response rate as a first-line treatment.
“The analysis included 52 patients (median age, 59.5 years) who had not undergone prior chemotherapy for metastatic breast cancer. Twenty-one patients had previously received trastuzumab and 31 had not. A median of 23 months had passed since previous treatment.
“Patients received 1.4 mg/m2 IV eribulin mesylate on days 1 and 8 of a 21-day cycle. They also received an initial trastuzumab dose of 8 mg/kg, followed by 6-mg/kg doses on day 1 of each cycle. Median treatment duration was approximately 30 weeks.
“Researchers reported similar rates of objective clinical response (62% vs. 77%) and clinical benefit (81% vs. 87%) between patients who had received prior trastuzumab and those who had not.”
Editor’s note: This story is about a clinical trial—a research study with volunteer patients. The goal of the trial was to test a post-surgery breast cancer treatment that combines the drugs lapatinib (Tykerb) and trastuzumab (Herceptin), and compare the combination to either drug on its own. All patients involved had early stage breast cancer that tested positive for HER2. The study found good tumor shrinkage rates for the combination treatment, but found no difference in overall survival time between patients who took the combo versus patients treated with a single drug.
“The phase III NeoALTTO trial showed a significantly improved pathologic complete response rate with lapatinib (Tykerb) plus trastuzumab (Herceptin) vs either alone in women with HER2-positive early breast cancer. As reported in The Lancet Oncology by de Azambuja et al, the combination was not associated with any benefit in the secondary endpoints of event-free survival or overall survival, although the investigators noted that the trial was not powered to detect survival differences. Significantly better event-free survival and overall survival were observed in patients with pathologic complete response, with the association in event-free survival being significant in the combination group…
“In this open-label trial, 455 patients were randomly assigned between January 2008 and May 2010 to receive oral lapatinib at 1,500 mg (n = 154), intravenous (IV) trastuzumab at a 4 mg/kg loading dose followed by 2 mg/kg (n = 149), or lapatinib at 1,000 mg plus trastuzumab (n = 152) for 6 weeks, followed by an additional 12 weeks of the assigned anti-HER2 therapy in combination with weekly paclitaxel 80 mg/m². Definitive surgery was performed at 4 weeks after the last dose of paclitaxel. After surgery, patients received three cycles of FEC (fluorouracil at 500 mg/m², epirubicin at 100 mg/m², cyclophosphamide at 500 mg/m²) given IV every 3 weeks followed by 34 weeks of the same assigned neoadjuvant anti-HER2 therapy.
“Pathologic complete response was observed in 51.3% of the combination recipients vs 29.5% of the trastuzumab recipients (P = .0001), and there was no difference in pathologic complete response between the trastuzumab group and the lapatinib group (24.7%, P = .34).”
“Approximately 15% of patients with breast cancer have tumors that overexpress the HER2 protein and these patients can benefit from HER2-targeted therapies. The American Society of Clinical Oncology recently released a clinical practice guideline on systemic therapy for patients with advanced HER2-positive breast cancer, published in the Journal of Clinical Oncology. The rationale for the guideline is that several new agents have become available for treatment of metastatic HER2-positive breast cancer since the approval of trastuzumab (Herceptin).
“Up to half of all patients with HER2-positive metastatic breast cancer develop brain metastases over time. Recommendations for the management of brain metastases in patients with HER2-positive breast cancer are detailed in another recently released companion guideline.”
Editor’s note: Click through to the full article (arrow button to the right of the title) to see the recommendations.
“At a median follow-up of 8 years, patients receiving trastuzumab (Herceptin) sequentially after chemotherapy and radiotherapy in the Herceptin Adjuvant (HERA) trial had a low incidence of cardiac events and these were reversible in the vast majority of patients. This long-term assessment confirms and extends previous reports of cardiac safety.
“The three-arm HERA trial compared 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer. ‘This is the first time that results of the 2-year trastuzumab arm have been reported, and the follow-up time has doubled,’ researchers reported in the Journal of Clinical Oncology.
“Eligible patients had a left-ventricular ejection fraction of at least 55% following neoadjuvant chemotherapy with or without radiotherapy and cardiac function was closely monitored. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of the 1,673 patients receiving 2 years of trastuzumab and 5.2% of the 1,682 patients receiving 1 year of trastuzumab.”
Editor’s note: This story discusses the results of a study that investigated the effects of the drug trastuzumab (brand name Herceptin) on cardiac health. The study involved 5,102 patients with HER2-positive, early-stage breast cancer. All of the patients had been previously treated. Patients were given trastuzumab as an adjuvant therapy—a treatment given after the main treatment to keep cancer from returning. Researchers found a low incidence of adverse cardiac events for the patients. However, they say that each patient should still have a cardiac assessment before and while taking trastuzumab to ensure that any problems are detected early.
The gist: A recent clinical trial found that the drug trastuzumab (Herceptin) improves survival and lowers the risk of recurrence for women with HER2-positive, locally advanced breast cancer. Patients in the trial received Herceptin as part of both neoadjuvant (before surgery) and adjuvant (after surgery) treatment. The researchers followed the patients for five years after treatment.
“As reported by Gianni et al in The Lancet Oncology, long-term follow-up of women with HER2-positive locally advanced breast cancer receiving neoadjuvant chemotherapy alone vs with neoadjuvant and adjuvant trastuzumab (Herceptin) in the phase III NOAH trial has shown continued event-free survival benefit of trastuzumab treatment and a strong association of event-free survival with pathologic complete response rate in trastuzumab recipients.
“In this open-label trial, 235 women with HER2-positive locally advanced or inflammatory breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (n = 118) or with 1 year of trastuzumab given concurrently with neoadjuvant chemotherapy and continued after surgery. (A parallel group with HER2-negative disease received neoadjuvant chemotherapy alone; outcomes in this group are not reported here.)”