Last month, the annual American Society of Clinical Oncology (ASCO) meeting took place in Chicago. Thousands of oncologists, patients, and journalists gathered to learn about the most recent developments in cancer research and treatment. Here are some breast cancer highlights from the meeting:
Triple negative breast cancer (TNBC) is considered more responsive to treatment with immune checkpoint drugs than any other type of breast cancer. So far, these drugs have primarily been explored in metastatic TNBC, in combination with chemotherapy. The combination of “anti-PD-L1” and “anti-PD-1” immune checkpoint drugs with chemotherapy has now been examined in early-stage TNBC, in which a breast tumor can be surgically removed after neoadjuvant chemotherapy. Continue reading…
“In a new study, Yale researchers identified a novel genetic defect that prevents brain tumor cells from repairing damaged DNA. They found that the defect is highly sensitive to an existing FDA-approved drug used to treat ovarian cancer—a discovery that challenges current practice for treatment of brain tumors and other cancers with the same genetic defect, said the scientists.
“The study was published on Feb. 1 by Science Translational Medicine.
“Certain malignant brain tumors and leukemias have mutations in genes known as IDH1 and IDH2. The mutations render the cancers sensitive to treatment with radiation therapy or chemotherapy, significantly increasing the survival time for patients with the mutations. To better understand this sensitivity, a cross-disciplinary team of researchers led by Yale created models of the mutation in cell cultures.”
“Olaparib (Lynparza) has received an FDA breakthrough therapy designation as a treatment for patients with BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer (mCRPC) in those who have received a prior taxane-based chemotherapy and at least either hormonal agent enzalutamide (Xtandi) or abiraterone acetate (Zytiga).
“The designation, which will accelerate the development and review of the first-in-class oral PARP inhibitor, is based on data from the phase II TOPARP-A trial that demonstrated that olaparib monotherapy had an overall response rate (ORR) of nearly 90% in a biomarker-defined subgroup of patients who had DNA-repair defects.“
“Joanne Blum, MD, PhD, breast medical oncologist, director, Hereditary Cancer Risk Program, Baylor Charles A. Sammons Cancer Center, discusses the function of the oral PARP inhibitor talazoparib (BMN 673) in BRCA mutation subjects with locally advanced and/or metastatic breast cancer. Blum says the BRCA mutation works in combination with talazoparib in order to better cut off the appropriate pathways for the tumors.
“Blum said during the phase I trial that looked at talazoparib, patients experienced grade 1 neutropenia, cytopenia and fatigue. Blum added that the toxicities were very mild.”
“A combination of two molecularly targeted drugs, olaparib (Lynparza) and the investigational agent AZD5363, was safe and yielded responses in patients with a variety of cancer types, including breast, ovarian, and prostate cancers, regardless of BRCA1/2-mutation status, according to data from the ComPAKT phase I clinical trial presented at the AACR Annual Meeting 2015, held April 18 to 22 in Philadelphia (Abstract CT323).
“ ‘In this clinical trial, we evaluated for the first time whether it is possible to safely combine the investigational AKT inhibitor AZD5363 with olaparib, a PARP [poly ADP-ribose polymerase] inhibitor recently approved by the U.S. Food and Drug Administration for treating advanced ovarian cancer associated with defective BRCA genes,’ said Timothy Yap, MD, PhD, National Institute for Health Research Biomedical Research Centre Clinician-Scientist and Consultant Medical Oncologist at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.
“ ‘Here, we are reporting results from the dose-escalation portion of the trial, which showed that it was indeed possible to combine these drugs safely,’ continued Dr. Yap. ‘We also observed that several different cancer types responded to the combination, including cancers without BRCA1/2 mutations. These early results are very exciting because preclinical data had suggested that the olaparib and AZD5363 combination had the potential to be effective in a much wider population of patients than just those harboring germline BRCA1/2 mutations.’ “
The gist: Patients with advanced ovarian cancer who have already had three to eight treatments might benefit from a new treatment that combines the drugs olaparib, paclitaxel, and carboplatin. That was the insight from a recent clinical trial—a research study with volunteer patients. The clinical trial found the combination treatment to be safe and effective at shrinking tumors, especially for women with BRCA mutations.
“A phase Ib clinical trial of the tablet form of olaparib, a PARP inhibitor, in combination with paclitaxel and carboplatin chemotherapy in heavily pretreated patients with advanced-stage ovarian cancer finds the drug to be safe and effective, especially in those women with BRCA gene mutations. The study by Rivkin et al was presented at the Marsha Rivkin Center for Ovarian Cancer Research–AACR 10th Biennial Ovarian Cancer Research Symposium, held September 8 to 9, in Seattle…
“The purpose of this study was to establish the maximum-tolerated dose of olaparib and to evaluate dose-limiting toxicities and response to therapy of the tablet form of olaparib plus carboplatin and paclitaxel in women with stage III or IV ovarian cancer. The researchers enrolled 14 heavily pretreated (from three to eight prior therapies) patients in the study, aged 42 to 77. All the patients were tested for BRCA2 and BRCA2 gene mutations.
“Patients received paclitaxel and carboplatin weekly for 3 out of 4 weeks, with increasing doses of olaparib. The maximum tolerated dose of olaparib was found to be 150 mg twice daily for 3 consecutive days of each week of each cycle.”
Shen Y, Rehman FL, Feng Y, Boshuizen J, et al. Clinical Cancer Research. Jul 23, 2013.
“Purpose: PARP1/2 inhibitors are a class of anticancer agents that target tumor-specific defects in DNA repair. Here, we describe BMN 673, a novel, highly potent PARP1/2 inhibitor with favorable metabolic stability, oral bioavailability, and pharmacokinetic properties. Experimental Design: Potency and selectivity of BMN 673 was determined by biochemical assays. Anticancer activity either as a single-agent or in combination with other antitumor agents was evaluated both in vitro and in xenograft cancer models…Conclusion: BMN 673 is currently in early-phase clinical development and represents a promising PARP1/2 inhibitor with potentially advantageous features in its drug class.“
A phase II clinical trial is being held to investigate the effect of an experimental drug, ABT-888, on castration-resistant prostate cancer (CRPC) in patients who have a genetic mutation known as a TMPRSS2:ERG gene fusion. In lab studies, ABT-888 used in combination with the prostate cancer drug abiraterone (Zytiga), helped shrink prostate cancer tumors and was especially effective for shrinking tumors that had the genetic mutation. The clinical trial is being led by investigators at the University of Michigan Comprehensive Cancer Center and conducted at multiple sites throughout the country. For more information about this trial, “A Randomized Gene Fusion-Stratified Phase II Trial of Abiraterone with or without ABT-888 for Patients with Metastatic Castration-Resistant Prostate Cancer,” call the U-M Cancer Answerline at 800-865-1125.
“A new clinical trial is testing whether targeting treatments to a genetic anomaly can lead to better treatments for castration-resistant metastatic prostate cancer. The trial, led by investigators at the University of Michigan Comprehensive Cancer Center, is being conducted at 11 sites throughout the country.”