Pfizer Submits NDA For Breast Cancer Drug Palbociclib Combined With Letrozole

Editor’s note: Before a new cancer treatment can be prescribed by doctors in the U.S., it must be approved by the U.S. Food and Drug Administration (FDA). Recently, the drug company Pfizer submitted an application to the FDA in the hopes that its new breast cancer treatment might be approved. The treatment combines two drugs called palbociclib and letrozole. It is specifically meant for treating advanced or metastatic breast cancer in post-menopausal women whose tumors have tested ER+ and HER2-. In addition, the women must not have already taken any other cancer treatments that travel through the bloodstream. The new treatment has performed well in a clinical trial with volunteer patients.

“Pharma giant Pfizer, Inc. ( PFE ) announced Monday that it submitted a New Drug Application or NDA, to the U.S. Food and Drug Administration or FDA, for palbociclib, in combination with letrozole, as first-line systemic treatment advanced or metastatic breast cancer in post-menopausal women.

” ‘Today’s submission marks an important milestone for Pfizer and palbociclib, and a potential advance for women with advanced breast cancer,’ said Garry Nicholson, President, Pfizer Oncology.

” is an investigational oral targeted agent that selectively inhibits cyclin-dependent kinases 4 and 6 to regain cell cycle control and block tumor cell proliferation.

“The NDA seeks approval for the treatment of postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received previous systemic treatment for their advanced disease.”

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.”

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.”

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.

Long-Term Follow-up Confirms Low Incidence of Cardiac Events Associated With Trastuzumab

“At a median follow-up of 8 years, patients receiving trastuzumab (Herceptin) sequentially after chemotherapy and radiotherapy in the Herceptin Adjuvant (HERA) trial had a low incidence of cardiac events and these were reversible in the vast majority of patients. This long-term assessment confirms and extends previous reports of cardiac safety.

“The three-arm HERA trial compared 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer. ‘This is the first time that results of the 2-year trastuzumab arm have been reported, and the follow-up time has doubled,’ researchers reported in the Journal of Clinical Oncology.

“Eligible patients had a left-ventricular ejection fraction of at least 55% following neoadjuvant chemotherapy with or without radiotherapy and cardiac function was closely monitored. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of the 1,673 patients receiving 2 years of trastuzumab and 5.2% of the 1,682 patients receiving 1 year of trastuzumab.”

Editor’s note: This story discusses the results of a study that investigated the effects of the drug trastuzumab (brand name Herceptin) on cardiac health. The study involved 5,102 patients with HER2-positive, early-stage breast cancer. All of the patients had been previously treated. Patients were given trastuzumab as an adjuvant therapy—a treatment given after the main treatment to keep cancer from returning. Researchers found a low incidence of adverse cardiac events for the patients. However, they say that each patient should still have a cardiac assessment before and while taking trastuzumab to ensure that any problems are detected early.

AbbVie Initiates Veliparib Phase III Trial in BRCA-mutated Advanced Breast Cancer Patients

“AbbVie has initiated its Phase III trial investigating the safety and efficacy of the investigational PARP inhibitor veliparib in combination with carboplatin and paclitaxel in advanced breast cancer patients.

“In the double-blind study, researchers will randomize nearly 300 patients to receive either veliparib, plus the carboplatin/paclitaxel combination, or just the chemotherapy regimen. Metastatic or locally advanced breast cancer patients enrolled in the trial will have to have tumors that are HER2 negative, but positive for BRCA1/2 mutations. AbbVie is working with Myriad Genetics to use its BRACAnalysis test to gauge BRCA mutations in study subjects.

“Researchers will assess in the study whether adding veliparib significantly increases patients’ progression-free survival compared to treatment with only chemotherapy. Other endpoints in the study are overall survival, clinical benefit rate, objective response rate, and duration of response.”

Editor’s note: Clinical trials are research studies that test new treatments on volunteer patients. In many clinical trials, some patients receive the new drug being tested, and for comparison, some patients receive “standard of care” treatment, meaning a U.S. Food and Drug Administration (FDA)-approved treatment that their oncologists would likely have considered for them. This story discusses a new clinical trial that is testing a drug called veliparib. The trial is enrolling people with advanced breast cancer who are HER2 negative and have BRCA1/2 mutations. Some of the patients will be treated with standard chemotherapy (a combination of the drugs carboplatin and paclitaxel), and some will receive veliparib PLUS standard chemotherapy. The trial is randomized, meaning patients will not get to choose which of the two treatments they receive. The goal of the clinical trial is to figure out whether adding veliparib to the chemo improves outcomes for patients.

Continued Event-Free Survival Benefit of Neoadjuvant/Adjuvant Trastuzumab in HER2-Positive Locally Advanced Breast Cancer

The gist: A recent clinical trial found that the drug trastuzumab (Herceptin) improves survival and lowers the risk of recurrence for women with HER2-positive, locally advanced breast cancer. Patients in the trial received Herceptin as part of both neoadjuvant (before surgery) and adjuvant (after surgery) treatment. The researchers followed the patients for five years after treatment.

“As reported by Gianni et al in The Lancet Oncology, long-term follow-up of women with HER2-positive locally advanced breast cancer receiving neoadjuvant chemotherapy alone vs with neoadjuvant and adjuvant trastuzumab (Herceptin) in the phase III NOAH trial has shown continued event-free survival benefit of trastuzumab treatment and a strong association of event-free survival with pathologic complete response rate in trastuzumab recipients.

“In this open-label trial, 235 women with HER2-positive locally advanced or inflammatory breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (n = 118) or with 1 year of trastuzumab given concurrently with neoadjuvant chemotherapy and continued after surgery. (A parallel group with HER2-negative disease received neoadjuvant chemotherapy alone; outcomes in this group are not reported here.)”

Ohio State Partners with MedVax to Bring a Cancer Peptide Vaccine to Patients

“The Ohio State University, through the Ohio State Innovation Foundation, has signed an exclusive world-wide licensing agreement with MedVax Technologies, Inc., for the licensing of groundbreaking cancer peptide vaccine technologies.

“The anticancer vaccine technologies are designed for the treatment and prevention of cancers associated with the HER2 protein. These include breast, ovarian, lung, colon and pancreatic cancers, and gastrointestinal stromal tumors. The commitment by MedVax will allow innovative clinical trials for various cancers to be conducted in the near future.”

Editor’s Note: Cancer vaccines are a type of “immune therapy,” which means that they boost a patient’s immune system to fight cancer. To learn more about immune therapies for lung cancer, read our blog feature on the topic.