​​A Presurgery Combination Therapy May Improve Outcomes for Women With HER2-positive Breast Cancer

Excerpt:

“Results from the I-SPY 2 TRIAL show that a neoadjuvant (presurgery) therapy combination of the antibody-drug conjugate trastuzumab emtansine (T-DM1; Kadcyla) and pertuzumab (Perjeta) was more beneficial than paclitaxel plus trastuzumab for women with HER2-positive invasive breast cancer, according to research presented here at the AACR Annual Meeting 2016, April 16-20.

“In this portion of the I-SPY2 TRIAL, the investigators tested if T-DM1 plus pertuzumab could bring a substantially greater proportion of patients to the primary endpoint of pathological complete response [pCR] compared with paclitaxel plus trastuzumab. They also examined whether this combination could meet that goal without the need for patients to receive paclitaxel. pCR is an outcome in which, following neoadjuvant therapy, no residual invasive cancer is detected in the breast tissue and lymph nodes removed during surgery.”

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TDM-1 With Docetaxel/Pertuzumab Offers Benefit in Advanced HER2-Positive Breast Cancer

Excerpt:

“Combining trastuzumab emtansine with docetaxel both with and without pertuzumab yielded promising efficacy in a phase Ib/IIa study of patients with HER2-positive locally advanced (LABC) or metastatic breast cancer (MBC). Many patients, however, required dose reductions due to toxicity.

“Trastuzumab emtansine (T-DM1) is a drug-antibody conjugate, and has been shown to offer significant survival benefits in phase III trials of HER2-positive metastatic breast cancer. ‘In preclinical studies, T-DM1 exhibited enhanced antitumor activity when combined with docetaxel or pertuzumab,’ wrote study authors led by Miguel Martin, MD, PhD, of Hospital General Universitario Gregorio Marañón in Madrid.”

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Pertuzumab Not Cost Effective in Metastatic HER2-Positive Breast Cancer

“Though the addition of pertuzumab to docetaxel and trastuzumab as first-line therapy for HER2-positive breast cancer has been shown to yield a substantial survival benefit, a new analysis shows that there is very little chance that pertuzumab would be cost effective in the United States.

“The CLEOPATRA trial showed that pertuzumab along with docetaxel and trastuzumab (THP) resulted in a median survival in HER2-positive metastatic breast cancer patients of 56.5 months, compared with only 40.8 months for the latter two drugs alone (TH). ‘These exceptional results come at a price,’ wrote researchers led by Ben Y. Durkee, MD, PhD, of Stanford University in California. ‘Our work shows that an insurer could expect to pay $4,649 per week for the THP regimen at Medicare rates. Private contractors and smaller entities would pay more.’

“The researchers used a decision-analytic Markov model to evaluate the regimen’s cost effectiveness, based on the study population from CLEOPATRA and the assumed number of patients for whom the THP regimen would be recommended in the metastatic setting. Results were published online ahead of print in the Journal of Clinical Oncology.”


Roche's Perjeta Regimen Approved in Europe for Use Before Surgery in Early Stage Aggressive Breast Cancer

“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Commission (EC) has approved the use of Perjeta® (pertuzumab) in combination with Herceptin® (trastuzumab) and chemotherapy for the neoadjuvant treatment (use before surgery) of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer at high risk of recurrence. The Perjeta regimen is the first neoadjuvant breast cancer treatment approved by the EC based on pCR data.

“Every year in Europe nearly 100,000 people are diagnosed with HER2-positive breast cancer, an aggressive type of the disease that is more likely to progress than HER2-negative cancer.1,2 Treating people with breast cancer early, before the cancer has spread, may improve the chance of preventing the disease from returning. Neoadjuvant treatment is given before surgery and is aimed at reducing tumour size so it is easier to surgically remove. pCR is achieved when there is no tumour tissue detectable at the time of surgery in the affected breast or in the affected breast and local lymph nodes. It is a common measure of neoadjuvant treatment effect in breast cancer and it can be assessed more quickly than traditional endpoints in eBC.

“ ‘Today’s approval is a significant milestone in the neoadjuvant treatment of HER2-positive early breast cancer, bringing Perjeta to patients years earlier than typical adjuvant treatment,’ said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head, Global Product Development. ‘We are committed to making the Perjeta regimen available to appropriate patients in the EU as early as possible.’ “


More Lessons from CLEOPATRA Trial: Benefits of Adding Perjeta

“Clinical trials generate massive amounts of data, which can be difficult to summarize in a 10-minute presentation at a medical conference.

“However, every study and every presentation related to the study have ‘money slides,’ the critical information for clinicians, researchers, and patients. Homing in on money slides can help reduce the time, effort, and confusion related to sorting out the results and meaning of clinical studies.

“At the 2014 meeting of the European Society of Medical Oncology, investigators reported practice-changing results from a randomized clinical trial in advanced breast cancer. In the accompanying video, Joseph Sparano, MD, of Albert Einstein College of Medicine and Montefiore Medical Center in New York City, uses the concept of money slides to offer a concise yet complete assessment of the CLEOPATRA trial results and implications.”


The Role of Pertuzumab in Treating HER2+ Breast Cancer


Pertuzumab (Perjeta) is a relatively new drug that targets HER2, a protein found at higher-than-normal levels in about 15% to 20% of all breast cancers. Too much HER2 leads to tumor growth. Currently, all newly diagnosed breast cancer patients have their tumors’ HER2 levels tested. Knowing whether a patient’s HER2 levels are abnormally high (HER2-positive) or normal (HER2-negative) is a major factor in choosing a treatment, thanks to the availability of trastuzumab (Herceptin) and, now, other HER2-targeted drugs such as Perjeta, T-DM1 (Kadcyla), and lapatinib (Tykerb). These drugs are all used to treat HER2-positive patients. Continue reading…


TDM-1 Trial Disappoints in HER2-Positive Breast Cancer

The gist: A clinical trial that tested a new drug called TDM-1 (Kadcyla) found disappointing results for patients with metastatic, HER2-positive breast cancer. The trial found that treatment with T-DM1 plus the drug pertuzumab is no better than treatment with trastuzumab plus chemotherapy. For more on TDM-1, see this recent news about its potential benefits for patients whose cancer has spread to the central nervous system (CNS).

“Results of the anticipated phase III MARIANNE trial found that HER2-positive metastatic breast cancer patients treated with trastuzumab emtansine (T-DM1) plus pertuzumab had similar progression-free survival (PFS) compared with those treated with trastuzumab plus a taxane-based chemotherapy.

“Though the trial met its noninferiority endpoint, showing a similar PFS in the first-line setting between the two combination therapies along with T-DM1 alone, it failed to demonstrate that T-DM1 performs better than trastuzumab plus chemotherapy.

“The study has been anticipated by clinicians as two of the treatment arms do not include a taxane, which often causes patients to lose their hair, among other toxicities. The full results of the study will be presented at a future medical meeting…

“ ‘In my opinion, given the substantial survival associated with [docetaxel plus trastuzumab and pertuzumab of over 56 months], it remains the current first-line standard regimen especially for those patients who have never been exposed to trastuzumab,’ said Hurvitz.”


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.’ “