“A pair of drugs already on the market appear to reduce the recurrence of breast cancer in women who’ve already undergone treatment, two new clinical trials show.
“The chemotherapy drug capecitabine (Xeloda) seems to reduce by nearly a third the risk of breast cancer recurrence if women receive the drug following surgery to remove their cancer, researchers were to report Wednesday at the 2015 San Antonio Breast Cancer Symposium.
“In addition, an osteoporosis medication called denosumab appears to reduce recurrence risk by 18 percent in women who have HR-positive breast cancer, a second study reports.”
“Treatment with the chemotherapy agent capecitabine increased disease-free survival for women with HER2-negative breast cancer that was not eliminated by presurgery chemotherapy, according to results from the phase III CREATE-X clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8-12.
“Treatment given to shrink or eliminate a tumor before surgery is called neoadjuvant therapy. In some patients with breast cancer treated with neoadjuvant chemotherapy, residual invasive cancer can be detected in breast tissue samples and lymph nodes removed during surgery. These patients tend to have worse long-term outcomes compared with women who respond completely to neoadjuvant therapy.
” ‘It has been suggested that patients with residual invasive disease after neoadjuvant chemotherapy have chemoresistant breast cancer, but there have been no large-scale clinical trials to test whether adjuvant systemic chemotherapy is beneficial for these patients,’ said Masakazu Toi, MD, PhD, a professor at Kyoto University Hospital in Japan, and founder and senior director of the Japan Breast Cancer Research Group (JBCRG). ‘CREATE-X was designed to evaluate this clinical question by testing whether capecitabine could improve disease-free survival for patients with residual invasive disease after neoadjuvant chemotherapy.’ “
Erika P. Hamilton, MD, associate director, Breast Cancer and Gynecologic Cancer Research Program, principal investigator, Sarah Cannon Research Institute, on ONT-380 for HER2-positive breast cancer and the treatment’s ability to cross the blood-brain barrier. Hamilton says the reason ONT-380’s ability to cross that barrier is important is because patients with HER2-positive breast cancer have a predilection to develop brain metastases.
She added that ONT-380 was proven to be effective when combined with capecitabine (Xeloda) and trastuzumab (Herceptin), though sometimes a combination of all three proved most useful. ONT-380 is a HER2-specific inhibitor and showed promising results when tested in patients with HER2-positive breast cancer who had previously received trastuzumab and T-DM1.
“Treatment with capecitabine and temozolomide (CAPTEM) is an effective therapy for patients with metastatic pancreatic neuroendocrine tumors (pNETs), but the efficacy of several predictive markers previously thought to determine which patients might respond to the regimen could not be validated, according to a presentation at the 2015 NANETS Symposium.
“ ‘In our study we tried to assess the role of potential predictors of response to temozolomide-based regimens in metastatic pNETs,’ according to lead author Mauro Cives, MD, who presented the findings at the 2015 North American Neuroendocrine Tumor Society symposium. The markers the investigators evaluated were expression of MGMT, proliferative activity, and ALT activation.
“Investigators looked at 143 patients with metastatic pNETs treated at Moffitt who had undergone therapy with CAPTEM and retrospectively evaluated them for radiographic response. ‘This is the largest reported cohort of pNET patients treated with temozolomide-based chemotherapy,’ said Cives, a research associate in the Department of GI Oncology at the Moffitt Cancer Center and Research Institute in Tampa, Florida.”
Pancreatic neuroendocrine tumors (PNETs) constitute only about 3% to 5% of all pancreatic cancers. Compared to the most common pancreatic cancer—adenocarcinoma (aka exocrine tumors), PNETs have a longer disease course and better prognosis; the 5-year survival rate is 42% for PNETs, but only about 5% to 6% for adenocarcinomas. When PNETs are localized, they can usually be removed by surgery. However, PNETs tend to metastasize, most often to the liver, and present a formidable treatment challenge at this stage. Continue reading…
“The Cancer Treatment Centers of America (CTCA) at Western Regional Medical Center in Arizona recently started a Phase Ib/II clinical trial called NivoPlus (NCT02423954) to test a new investigational immunotherapeutic treatment for several advanced cancers. This novel immunotherapeutic approach is based on the combination of an immunotherapy drug (nivolumab) with chemotherapy drugs (irinotecan, temsirolimus and a combination of irinotecan and capecitabine) which have been approved by the U.S. Food and Drug Administration (FDA).
“Cancer immunotherapy is defined as the use of the body’s own immune system to help fight cancer. In 2013, the renowned Science magazine established that cancer immunotherapy had been the scientific breakthrough of the year, and recent advances in the field have yielded promising results for cancer patients.
“Nivolumab is an antibody against the programmed death 1 (PD-1) receptor, an immune checkpoint that if inhibited results in the stimulation of the body’s antitumor immunity. Nivolumab has been approved by the FDA for the treatment of advanced melanoma in December 2014 and metastatic squamous non-small cell lung cancer in March 2015. Its combination with chemotherapeutic drugs is expected to activate the body’s immune system and improve the response to cancer.”
The gist: In a recent clinical trial with locally advanced or metastatic breast cancer patients, women who took the drug eribulin did just as well as women who took capecitabine. The results were particularly strong for women with triple-negative breast cancer. All women in the trial had received previous treatment with anthracycline- or taxane-based chemotherapy. More research is planned to determine just how beneficial eribulin might be.
“An international research team, led by Dartmouth’s Peter A. Kaufman, MD, published findings in the Journal of Clinical Oncology demonstrating that, while not superior to capecitabine, eribulin is an active and well-tolerated therapy in women with metastatic breast cancer (MBC) receiving this therapy as a first, second, or third line chemotherapy regimen. Additionally, these patients had all been previously treated with both an anthracycline and a taxane in either the adjuvant or metastatic setting. This study is the first to address the use of eribulin early in the course of metastatic breast cancer, specifically either the first or second line setting.
” ‘Additionally, it is of great interest that subset analysis suggests that eribulin may be particularly active and effective in triple negative MBC, which is known to be an aggressive subset of breast cancer, and one associated unfortunately with a particularly poor prognosis overall,’ said Kaufman.
“Eribulin has been approved in numerous countries in the third line or latter setting for the treatment of MBC, and is increasingly widely used. It is the only chemotherapeutic agent shown to have a survival benefit for patients with MBC in the third line or latter chemotherapeutic setting. Given previous research findings, and now findings from this large international trial, there has been great interest from oncologists and other clinicians in the potential impact that eribulin might have earlier in the course of MBC.”
The gist: People whose HER2-positive breast cancer has spread to their central nervous system (CNS) might survive longer if they are treated with the drug Kadcyla than if they take capecitabine plus lapatinib. That was the conclusion of a recent clinical trial with volunteer patients. Our Chief Scientist speculates that the mild side effects of Kadcyla compared to those of the capecitabine/lapatinib combo might also make it a better choice.
“Patients with HER-2–positive advanced breast cancer treated with ado-trastuzumab emtansine experienced similar rates of central nervous system progression as those treated with capecitabine plus lapatinib, according to study results.
“However, among patients with treated, asymptomatic central nervous system (CNS) metastases at baseline, those assigned the antibody–drug conjugate ado-trastuzumab emtansine (Kadcyla, Genentech) experienced significantly longer OS than those assigned capecitabine plus lapatinib (Tykerb, GlaxoSmithKline).
“Ian E. Krop, MD, of the department of medical oncology at Dana-Farber Cancer Institute and Harvard University School of Medicine, and colleagues conducted a retrospective, exploratory analysis of data from the phase 3 EMILIA study.
“The EMILIA study included 991 patients with HER-2–positive advanced breast cancer who underwent previous treatment with trastuzumab (Herceptin, Genentech) and a taxane. Researchers randomly assigned 495 patients to ado-trastuzumab emtansine, and the other 496 received capecitabine plus lapatinib. Treatment continued until disease progression.”