New Proposal for Combined Therapy Proves Effective Against a Notoriously Resistant HER2+ Breast Cancer Subtype

Note: This article discusses research that was performed in cells and in mice in the lab. Therefore, the results do not necessarily apply to humans. Nonetheless, they are promising. The research looked into treatment of a specific HER2+ breast cancer subtype known as p95HER2. The scientists found that this type of tumor might be successfully treated with a combination of chemotherapy and the targeted drug Herceptin. Clinical trials with volunteer patients will be needed to see if this holds true.

“Research led by Joaquín Arribas, Principal Investigator of the Vall d´Hebron Institute of Oncology´s (VHIO) Growth Factors Group, Director of Preclinical Research at VHIO, and ICREA Professor, has shown the combined strategy of chemotherapy plus trastuzumab (a selective therapy against HER2 receptors), as effective in reducing tumors of a specific HER2+ breast cancer subtype known as p95HER2. Recently published in the Journal of the National Cancer Institute (JNCI), this study signposts new therapeutic promise for patients with p95HER2-positive breast tumors, since, up until now, this subgroup has proven highly resistant to therapy. Funded through support received from the Spanish Association against Cancer (AECC), this research has also been carried out in collaboration with Atanasio Pandiella from the Cancer Research Center of Salamanca (CIC) and other organizations including the Breast Cancer Research Foundation (BCRF).”


Years After Treatment for HER2-Positve Early Stage Breast Cancer, Trastuzumab Continues to Show Life-Altering Benefit

“After following breast cancer patients for an average of eight-plus years, researchers say that adding trastuzumab (Herceptin) to chemotherapy significantly improved the overall and disease-free survival of women with early stage HER2-positive breast cancer.

“They found that the use of trastuzumab produced a 37 percent improvement in survival and a 40 percent reduction in risk of cancer occurrence, compared to patients treated with chemotherapy alone.

“These findings, published in the Journal of Clinical Oncology, demonstrate how important trastuzumab has been to the treatment of this form of breast cancer, says the study’s lead author, 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.

” ‘This long follow-up of patients shows that we have really altered the natural history of this disease,’ says Dr. Perez. ‘Herceptin works — and it works for a long period of time. The drug has impacted the lives of many women in the U.S. and worldwide.’

“HER2-positive breast cancer accounts for 15-20 percent of invasive breast cancers. Before the development of trastuzumab, women with early stage breast cancer faced a worse prognosis than those with HER2-negative breast cancer, including quicker relapse, higher incidence of metastasis, and shorter survival, according to Dr. Perez.”


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.'”


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.’ ”


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.”