The gist: Women with HER2-positive breast cancer whose tumors also have a mutation called PIK3CA might not respond as well to HER2-targeted treatments. Scientists looked at tumor samples from patients who had taken the drugs trastuzumab (Herceptin) and/or lapatinib (Tykerb). They had also taken neoadjuvant (before surgery) chemotherapy. Patients whose tumors had PIK3CA mutations had a significantly lower rate of treatment success. These findings highlight the need for more research into PIK3CA-targeted therapy. They also echo findings from other researchers.
“Patients with HER-2–positive breast cancer who harbored activating mutations in PIK3CA were considerably less likely to achieve total pathologic complete response to neoadjuvant HER-2–targeted therapies than patients who did not have PIK3CA mutations, according to findings in the randomized, phase 3 NeoALTTO trial.
“PIK3CA activating mutations are present in all subtypes of breast cancer. However, they are enriched in HER-2–positive and ER-positive disease, according to study background.
“José Baselga, MD, PhD, physician-in-chief and chief medical officer at Memorial Sloan Kettering Cancer Center, and colleagues investigated whether an association existed between PIK3CA mutation status and patients’ response to HER-2–targeted therapy.”
The gist: Recent research found that prostate cancer patients have similar survival rates whether they have androgen deprivation therapy (ADT) before or after tumor-removal surgery. The study focused on men with intermediate- or high-risk prostate cancer who were treated between 1995 and 2002.
“Patients with intermediate- or high-risk prostate cancer demonstrated similar biochemical relapse-free survival, distant metastasis-free survival and OS regardless of whether they received androgen deprivation in the neoadjuvant or adjuvant settings, according to study results.
“Patients with localized prostate cancer typically undergo androgen deprivation therapy (ADT) in the neoadjuvant setting, concurrent with radiation therapy.
“Michael A. Weller, MD,of Cleveland Clinic, and colleagues assessed whether patients who underwent ADT in the adjuvant setting experienced different outcomes.
“The analysis included 515 patients treated with radiation therapy and ADT from 1995 to 2002. Of these patients, 311 underwent ADT in the neoadjuvant setting, beginning 2 to 3 months before the start of radiation therapy. The other 204 patients underwent ADT in the adjuvant setting, immediately after the completion of radiation therapy.”
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…
The gist: Breast cancer patients being treated with the drug trastuzumab (Herceptin) receive the same benefits whether they take it intravenously (by IV) or as an injection.
“Subcutaneous trastuzumab demonstrated comparable safety and efficacy to IV trastuzumab in patients with HER-2–positive early breast cancer, according to results of an international randomized, open-label phase 3 study.
“Christian Jackisch, MD, PhD, of the Breast Cancer and Gynecology Cancer Center at Sana Klinikum Offenbach GmbH in Germany, and colleagues compared the pharmacokinetics, efficacy and safety of subcutaneous vs. IV trastuzumab (Herceptin, Genentech). The study included 596 women with HER-2–positive, operable, locally advanced or inflammatory breast cancer in the neoadjuvant/adjuvant setting.
“All women underwent treatment with eight cycles of neoadjuvant chemotherapy administered concurrently with trastuzumab. Trastuzumab was administered either via 3-weekly fixed doses of 600 mg or via the standard weight-based method.
“Patients continued treatment with trastuzumab for 1 year after surgery.”
The gist: Many women with HER2-positive breast cancer take the drug trastuzumab (aka Herceptin) along with chemotherapy after tumor-removal surgery to keep the cancer from returning. However, new research shows that women who have high levels of certain immune system cells in their tumors might not benefit from Herceptin. For these patients, chemotherapy might be just as effective at preventing the return of cancer as the chemo/Herceptin combo.
“HER2-positive breast cancers with a high level of immune cell infiltration might not benefit from the addition of trastuzumab (Herceptin) to chemotherapy, a trial analysis suggested.
“The 10% of patients with stromal tumor-infiltrating lymphocyte-predominant breast cancer in the Alliance N9831 trial showed similar recurrence-free survival (RFS) whether they received chemotherapy alone or with trastuzumab (10-year rate 90.9% versus 80.0%,P=0.21), Edith A. Perez, MD, of the Mayo Clinic in Jacksonville, Fla., and colleagues found.
“The rest showed, as expected, significantly better recurrence-free survival with addition of trastuzumab (10-year rate 79.6% versus 64.3%, hazard ratio 0.49, P=0.0003), they reported here at the San Antonio Breast Cancer Symposium.”
The gist: A new drug called PLX3397 will now be available through the innovative I-SPY 2clinical trial, which uses molecular testing to match breast cancer patients to the pre-surgery treatments most likely to work for them. The trial is open for participation by women with newly diagnosed, locally advanced breast cancer.
“Plexxikon Inc., a member of Daiichi Sankyo Group, and QuantumLeap Healthcare Collaborative today announced that Plexxikon’s drug candidate, PLX3397, has been selected for study in the I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2). I-SPY 2 is a standing phase 2 randomized, controlled, multicenter trial for women with newly diagnosed, locally advanced breast cancer (minimum of Stage 2) that is designed to test whether adding investigational drugs to standard chemotherapy is better than standard chemotherapy alone in the neoadjuvant setting (prior to surgery).
“I-SPY 2 is conducted by a consortium that brings together the Food and Drug Administration (FDA), National Cancer Institute (NCI), pharmaceutical companies, leading academic medical centers, and patient advocacy groups under its umbrella. The trial is sponsored by QuantumLeap Healthcare Collaborative (QLHC), a 501(c)(3) non-profit organization dedicated to accelerating healthcare solutions.
“The I-SPY 2 TRIAL employs a unique adaptive trial design to match experimental therapies with patients. Genetic or biological markers (‘biomarkers’) from individual patients’ tumors are used to screen promising new treatments, identifying which therapies are most effective in specific patient subgroups. Regimens that have a high Bayesian predictive probability of showing superiority in a 300 patient phase 3 confirmatory trial in at least one of 10 predefined signatures may ‘graduate’ from I-SPY. This high efficacy bar and rapid turnaround time allows the trial to identify the right drug for the right patient in the most expeditious fashion.”
The gist: Women with basal-like triple-negative breast cancer (TNBC) might benefit from adding either the drug bevacizumab (Avastin) or the drug carboplatin to their chemotherapy treatment before tumor-removal surgery (neoadjuvant chemotherapy). For non-basal-like TNBC patients, carboplatin shows similar benefit, but bevacizumab may actually worsen their treatment response.
“A study of women with triple-negative breast cancer (TNBC) has shown that women with the basal-like subtype of breast cancer had higher rates of pathologic complete response (pCR) with the addition of bevacizumab (Avastin) to neoadjuvant chemotherapy than did women with non–basal-like breast cancer. No difference in response was seen between the two subtypes for the addition of carboplatin.
“These results were part of a subtype analysis of the CALGB/Alliance 40603 study and were presented at the 2014 San Antonio Breast Cancer Symposium, held December 9–13 in San Antonio, Texas, by William M. Sikov, MD, associate director of clinical research for the program in women’s oncology at Women and Infants Hospital and associate professor of medicine at Alpert Medical School of Brown University in Providence, Rhode Island.
“Earlier this year, results of the initial study of 443 women published in the Journal of Clinical Oncology showed that the addition of carboplatin or bevacizumab to neoadjuvant chemotherapy in women with stage II to III TNBC increased rates of pCR. In the subtype analysis, Sikov and colleagues sought to identify subgroups of patients who were more or less likely to benefit from the addition of these therapies.
“In a clinical trial involving women with triple-negative breast cancer, patients who received the drugs carboplatin and/or bevacizumab in combination with standard chemotherapy prior to surgery were more likely to have their tumors disappear entirely from the breast, according to data presented by investigators during the 2014 San Antonio Breast Cancer Symposium.
“Although bevacizumab doesn’t reduce long-term rates of cancer recurrence, the results raise hopes that carboplatin can be an important part of the fight against triple-negative cancer, say the leaders of the study, which was organized by the Alliance for Clinical Trials in Oncology with extensive involvement of physician/scientists at Dana-Farber Cancer Institute.
“The investigators analyzed data from 360 patients with triple-negative breast cancer, the vast majority of whom had a form of the disease known as basal-like tumors. Triple-negative cancer, named for its cells’ lack of three key receptors, accounts for about 15-20 percent of all breast cancers and tends to be aggressive, but can often be treated successfully if caught early. Basal-like tumors are made up of cells that resemble the basal cells lining the milk ducts.
“In the trial, patients with triple-negative breast cancer were treated with ‘neoadjuvant” chemotherapy’ — which helps shrink tumors so they can be surgically removed — either alone or in combination with bevacizumab or carboplatin or both. (Bevacizumab prevents tumors from developing networks of blood vessels; carboplatin is a platinum-based chemotherapy agent.)”
The gist: Patients with intermediate- or high-risk prostate cancer who are prescribed treatment with leuprolide acetate before prostatectomy may benefit more if they also take abiraterone acetate (aka Zytiga).
“In a phase II study reported in the Journal of Clinical Oncology, Taplin et al found that the addition of neoadjuvant abiraterone acetate (Zytiga) to the luteinizing hormone–releasing hormone (LHRH) agonist leuprolide acetate resulted in greater suppression of intraprostatic androgens in patients with intermediate- or high-risk localized prostate cancer.
“In the study, 58 patients were randomly assigned to receive abiraterone plus leuprolide (n = 30) or leuprolide alone (n = 28) for 12 weeks followed by prostate biopsy. All patients then received 12 weeks of abiraterone plus leuprolide and underwent radical prostatectomy…
“The investigators concluded: ‘LHRH [agonist] plus [abiraterone acetate] treatment suppresses tissue androgens more effectively than LHRH [agonist] alone. Intensive intratumoral androgen suppression with LHRH [agonist] plus [abiraterone acetate] before prostatectomy for localized high-risk [prostate cancer] may reduce tumor burden.’ “