Kadcyla/Perjeta Combo Does Not Improve Outcomes for Patients with Advanced, Untreated, HER2-Positive Breast Cancer

The gist: Combining the breast cancer drugs Kadcyla and Perjeta does not seem to improve outcomes for advanced, HER2-positive patients, compared to Kadcyla alone or Herceptin plus chemotherapy. That was the conclusion of a recent clinical trial that tested the combo in people who had not yet been treated for their advanced cancer. Herceptin plus chemotherapy is a cheaper option than Kadcyla plus Perjeta.

“Patients who got a combination of Kadcyla and Perjeta lived without their disease worsening for a similar amount of time as those who got Kadcyla alone, or those receiving the older medicine Herceptin plus chemotherapy, the Basel, Switzerland-based company said in a statement today. The study, dubbed Marianne, looked at 1,095 patients with a genetic mutation known as HER2 whose cancer has spread and who haven’t already tried other treatments.

“A successful combination of Kadcyla and Perjeta may have helped Roche replace sales of Herceptin that the company would lose should that medicine face competition from cheaper copies in coming years. Herceptin was Roche’s third-biggest drug in the first nine months of this year, with revenue of 4.7 billion Swiss francs ($4.8 billion).”

CLEOPATRA Analysis Shows That HER2 Is Sole Marker Suitable for Selection of Pertuzumab/Trastuzumab-Based Treatment in Metastatic Breast Cancer

The gist: Some metastatic breast cancer patients can be treated with a combination of the drugs pertuzumab (Perjeta) and trastuzumab (Herceptin). New research shows that, when deciding whether to use the combo for a patient, the only tumor mutation an oncologist must consider is HER2. HER2 is one of many tumor mutations that could potentially be used to predict whether a certain treatment will work. The new research showed that, while only HER2 is necessary for the treatment decision, other biomarkers like HER3 and PIK3CA might help predict how well the treatment will work for a patient.

“In an analysis in the CLEOPATRA trial population reported in the Journal of Clinical Oncology, Baselga et al found that HER2 was the only biomarker suitable for use in selecting patients for first-line pertuzumab (Perjeta)/trastuzumab (Herceptin)-based treatment in patients with HER2-positive metastatic breast cancer…

“The study involved analysis of mandatory tumor and serum samples from 808 patients receiving first-line pertuzumab, trastuzumab, and docetaxel vs trastuzumab and docetaxel in CLEOPATRA. Samples were assessed (58%–99.8% assessable) for amphiregulin, betacellulin, EGF, transforming growth factor alpha,  EGFR, HER2, HER3, insulin-like growth factor 1 receptor, PTEN, phosphorylated AKT, PIK3CA, CMYC, serum HER2 extracellular domain (sHER2), and FCγR. The CLEOPATRA trial showed significant increases in progression-free survival and overall survival with the addition of pertuzumab…

“The investigators concluded: ‘Through comprehensive prospective analyses, CLEOPATRA biomarker data demonstrate that HER2 is the only marker suited for patient selection for the trastuzumab plus pertuzumab-based regimen in HER2-positive metastatic breast cancer. HER2, HER3, and PIK3CA were relevant prognostic factors.’ “

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.”

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.'”

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.’ ”