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 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.’ ”


Team Finds New Route for Ovarian Cancer Spread

The gist: In a patient with ovarian cancer, tumor cells can detach from the tumor and enter the bloodstream, spreading and potentially resulting in metastases in other organs. Recent research found that these so-called “circulating tumor cells” (CTCs) rely on a protein called HER3, which is found in unusually high amounts in the CTCs. Therefore, developing drugs that target HER3 could help thwart ovarian cancer metastasis. Indeed, some drugs designed for that purpose are already being tested in clinical trials.

“Circulating tumor cells spread ovarian cancer through the bloodstream, homing in on a sheath of abdominal fatty tissue where it can grow and metastasize to other organs, scientists at The University of Texas MD Anderson Cancer Center report in Cancer Cell.

” ‘This completely new way of thinking about ovarian cancer metastasis provides new potential avenues to predict and prevent recurrence or metastasis,’ said senior author Anil Sood, M.D., professor of Gynecologic Oncology and Reproductive Medicine and Cancer Biology.

“The researchers found the circulating tumor cells (CTCs) rely on HER3, a less-famous sibling of the HER2 receptor protein prominent in some breast cancers, to find their way to the omentum, a sheet of tissue that covers and supports abdominal organs.

“HER3’s heavy presence on these cells makes it a biomarker candidate and suggests possible therapeutic options to thwart ovarian cancer progression, the researchers noted. ‘The CTCs are not just a correlation, they seem to have a functionally important role in metastasis,’ Sood said.”