Herceptin Boosts Survival for Breast Cancer, Study Reports

“Adding the drug Herceptin to chemotherapy for certain breast cancer patients increases overall survival and reduces the risk of recurrence compared to chemotherapy alone, new research shows.

“The study found that adding a year of Herceptin (trastuzumab) to standard chemotherapy improved overall survival by 37 percent. The addition of Herceptin also boosted 10-year overall survival rates from 75 percent to 84 percent.

“And the 10-year disease-free survival rate went from 62 percent to 74 percent for those also taking Herceptin, the study found.

“The women who were given Herceptin were patients with a type of breast cancer known as HER2-positive, said study author Dr. Edith Perez at the Mayo Clinic in Jacksonville, Fla.

“Up to 20 percent of invasive breast cancers are HER2-positive, according to background information in the study. Too much human epidermal growth factor receptor 2 (HER2) helps breast cancer cells grow. Herceptin works by targeting HER2 proteins to stop cancer cell growth.

“The study is published online Oct. 20 in the Journal of Clinical Oncology. It was supported by the U.S. National Institutes of Health and others, including Genentech, the company that makes Herceptin.”


Neoadjuvant Chemotherapy Plus Two Anti-HER2 Agents Optimal for HER2-Positive Breast Cancer

The gist: Before surgery to remove a tumor, breast cancer patients might take neoadjuvant therapy to shrink the tumor or otherwise help ensure a more successful surgery. A recent study concludes that combining two HER2-targeted drugs with chemotherapy might be the best neoadjuvant treatment choice for women with HER2-positive breast cancer. The researchers compared data from patients who received different combinations of chemotherapy, trastuzumab (Herceptin), and lapatinib (Tykerb). Patients who received all three had the highest chance of having no more signs of an invasive tumor after the treatment.

“For women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, combining two anti-HER2 agents with chemotherapy is the most effective treatment modality in the neoadjuvant setting, according to a meta-analysis published in the Journal of the National Cancer Institute.

“The study by Nagayama et al found that chemotherapy with trastuzumab (Herceptin) plus lapatinib (Tykerb), or with trastuzumab plus pertuzumab (Perjeta), resulted in a statistically significantly larger number of patients achieving pathologic complete response than did chemotherapy alone, chemotherapy with a single targeted therapy, or two anti-HER agents without chemotherapy. Ranking of treatment arms indicated that chemotherapy with trastuzumab plus pertuzumab “had the highest probability of being the best treatment arm in terms of [pathologic complete response],” the investigators stated.

“ ‘The growing number of HER2-targeted agents has created the need to define the optimal neoadjuvant therapy for HER2-positive breast cancer,’ the researchers wrote in explaining the rationale for the study. While other trials have been conducted to compare treatments, ‘it is difficult to integrate information on the relative efficacy of all tested regimens, since each trial has compared only a few treatments,’ the investigators noted.”


Neratinib Plus Capecitabine Shows Activity in HER2-Positive Metastatic Breast Cancer

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).”


Roche Drugs Shown Effective in Breast and Skin Cancers

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.'”


Promising Results Shown with Targeted Approaches in Subsets of Non-Small Cell Lung Cancer

The gist: Two new targeted treatment approaches are showing promise for some lung cancer patients. Researchers are testing the targeted drug dabrafenib in a clinical trial—a research study with volunteer patients. Dabrafenib is meant to treat certain people who have already been treated for advanced non-small cell lung cancer (NSCLC) but who need additional treatment. The patients who participated in the trial had a tumor mutation called BRAF V600E. The study results supported dabrafenib as an effective treatment for these patients. In another clinical trial, researchers found that a combination of the drugs temsirolimus and neratinib had beneficial effects for people with advanced non-small cell lung cancer (NSCLC) whose tumors had mutations in the HER2 gene.

“The BRAF inhibitor dabrafenib has significant anti-tumour activity in patients with advanced BRAF V600E mutant non-small cell lung cancer whose disease has progressed after chemotherapy, according to phase II data presented at the ESMO 2014 Congress in Madrid, Spain.

” ‘Reports of lung cancers bearing mutations in BRAF have generated considerable interest because these mutations may be associated with increased sensitivity to BRAF tyrosine-kinase inhibiting agents,’ says lead author Dr David Planchard, pulmonary oncologist at the Gustav-Roussy Cancer Campus, Paris, France.

“Planchard says studies suggest that activating BRAF mutations are present in around 2% of lung carcinomas — approximately 80% of which are V600E mutations. The BRAF V600E mutations are frequently associated with shorter disease-free, overall survival, and lower response rates to platinum-based chemotherapy.

“This open-label phase II study involves patients with BRAF V600E mutant non-small cell lung cancer, treated with dabrafenib alone (150 mg, twice daily). The primary endpoint is investigator-assessed overall response rate, with secondary endpoints of progression-free survival, duration of response, overall survival, safety and tolerability, and population pharmacokinetics.”


Trial Shows Trastuzumab Should Remain as Standard of Care for HER2-Positive Breast Cancer

“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.”


Roche Breast Cancer Drug Perjeta Appears to Greatly Extend Patients’ Lives

“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.’ ”


PIK3CA Mutation May Reduce Efficacy of Anti-HER2 Treatments

The gist: Women with HER2-positive breast cancer whose tumors also have a mutation called PIK3CA might not respond as well to HER2-targeted treatments. Scientists looked at tumor samples from patients who had taken the drugs trastuzumab (Herceptin) and/or lapatinib (Tykerb). They had also taken neoadjuvant (before surgery) chemotherapy. Patients whose tumors had PIK3CA mutations had a significantly lower rate of treatment success. These findings highlight the need for more research into PIK3CA-targeted therapy.

“Newly diagnosed patients with HER2-positive breast cancer with tumors that harbor a PIK3CA mutation are not as likely to have a pathologic complete response (pCR) following HER2-targeted therapy plus neoadjuvant chemotherapy. This was the case regardless of whether patients were treated with single or combination HER2-targeted therapy. pCR rates were lowest for those patients with hormone receptor (HR)-positive, HER2-positive disease who harbored a PIK3CA mutation.

“This mutation may be a negative prognostic biomarker for HER2-positive patients. The study was published in the Journal of Clinical Oncology.

“According to the authors, this is the largest study to assess the link between PIK3CA mutations and pCR in HER2-positive disease.

“Only about one-third of women with HER2-positive breast cancer respond to anti-HER2 therapy—a treatment that has side effects and is costly. Still, all of these patients are ultimately treated with the same regimens because there are currently no assays that test whether a patient is likely to have an improved disease-free or overall survival from the therapy.”


Eribulin Plus Trastuzumab Safe, Effective in HER-2–Positive Metastatic Breast Cancer

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.”