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.”


Novel Immunotherapy Vaccine Decreases Recurrence in HER2 Positive Breast Cancer Patients

Editor’s note: This article discusses the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to test a new breast cancer treatment called GP2. GP2 is a cancer vaccine that works by boosting a patient’s own immune system to keep cancer from returning after treatment (recurrence). In the trial, it was shown to be safe and effective. The researchers also found that women with HER2-positive breast cancer who had taken the drug trastuzumab before GP2 treatment experienced no recurrence.

“A new breast cancer vaccine candidate, (GP2), provides further evidence of the potential of immunotherapy in preventing disease recurrence. This is especially the case for high-risk patients when it is combined with a powerful immunotherapy drug. These findings are being presented by The University of Texas MD Anderson Cancer Center at the 2014 American Society of Clinical Oncology’s Breast Cancer Symposium in San Francisco.

“One of only a few vaccines of its kind in development, GP2 has been shown to be safe and effective for breast cancer patients, reducing recurrence rates by 57%. Further, women with the highest overexpression of HER2 (known as HER2 +3) had no cancer recurrences when they were administered the vaccine after completing trastuzumab (Herceptin), a type of immunotherapy drug known as a monoclonal antibody. HER2 is an oncoprotein that promotes tumor growth and is expressed to some extent in 75-80% of breast cancers…

“We believe many more patients will benefit in some way from immunotherapy,” says Mittendorf. “The challenge will be identifying the right immunotherapeutic approach for each individual patient. When doctors are able to do that, cancer therapy, and immunotherapy specifically, will follow a more personalized approach.””


NeoALTTO Trial Shows No Benefit of Lapatinib Plus Trastuzumab in Secondary Survival Endpoints in HER2-Positive Early Breast Cancer

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).”


Puma Says Cancer Drug Meets Trial Goal, Shares Soar

The gist: A new drug called neratinib (aka PB272) has shown promising results in a clinical trial testing the drug in volunteer patients. The clinical trial involved patients with early-stage HER2-positive breast cancer. They were treated with the drug trastuzumab, and then received follow-up (“adjuvant“) treatment with neratinib. Adjuvant treatments are given to patients after primary treatment to prevent cancer from returning. Indeed, in this clinical trial, neratinib was shown to significantly lengthen the amount of time that passed without patients’ disease worsening.

“Puma Biotechnology Inc said its experimental breast cancer drug met its main goal in a late-stage trial.

“Shares of the company, which doesn’t have any drug in the market, tripled to $176.94 in extended trading.

“Puma said on Tuesday it plans to file for marketing approval of neratinib, code named PB272, in the first half of 2015.

“Adjuvant treatment with the drug showed a statistically significant improvement in disease-free survival of 33 percent versus patients on placebo, according to trial data.”


Saving the Heart in Breast Cancer Treatment

“Breast cancer awareness campaigns stress saving the breasts – but what about the heart? Breast cancer patients who are positive for the HER2 gene may be at increased risk for heart damage during chemotherapy, according to a new study. Cardio-oncology is a relatively new field of research, emerging as scientists and doctors understand the connections between cancer treatment and the heart.”


ASCO Clinical Practice Guideline: Systemic Therapy for Patients With Advanced HER2-Positive Breast Cancer

“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.