Most of the recent developments in prostate cancer treatment have addressed the timing and duration of androgen deprivation, who should receive radiation treatments, and the timing of the few available chemotherapy options. But this month’s big news is a welcome change: metastatic castration-resistant prostate cancers (mCRPCs) that harbor mutations in BRCA2 or one of a few other genes have a remarkable response to olaparib (Lynparza), a drug that inhibits the enzyme PARP1. Continue reading…
“A pioneering drug developed to treat women with inherited cancers can also benefit men with advanced prostate cancer, a major new clinical trial concludes.
“The trial is a milestone in cancer treatment as the first to show the benefits of ‘precision medicine’ in prostate cancer – with treatment matched to the particular genetic characteristics of a man’s tumour.
“Olaparib, the world’s first drug to reach the market targeted against inherited cancer mutations, was found to benefit as many as a third of patients with prostate cancer, including many who did not inherit cancer genes but whose tumours had acquired defects in DNA repair.”
“A combination treatment composed of the PARP inhibitor olaparib and the investigational PI3K inhibitor BKM120 demonstrated activity and safety for women with triple-negative breast cancer or high-grade serous ovarian cancer, according to study findings presented at the American Association for Cancer Research Annual Meeting.
“High-grade serous ovarian cancer and triple-negative breast cancer are similar in that they often have germline BRCA mutations, have a sensitivity to platinum agents and have high copy number alterations based on The Cancer Genome Atlas, according to study background. Further, preclinical data have suggested olaparib (Lynparza, AstraZeneca) is synergistic with BKM120 (Novartis) and BYL719 (Novartis) in both cancers.
“Ursula A. Matulonis, MD, medical director of gynecologic oncology at the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute and associate professor of medicine at Harvard University Medical School, and colleagues evaluated olaparib plus BKM120 in 12 patients with triple-negative breast cancer and 34 patients with high-grade serous ovarian cancer. Thirty-five patients had germline BRCA mutations.
“ ‘This is one area where we in ovarian cancer are in the forefront,’ Matulonis said during a press conference. ‘We are using an FDA-approved biomarker through germline BRCA status to basically say when a patient is eligible to receive olaparib.’ “
“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.’ “
“Combination treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib plus the phosphatidylinositol 3-kinase (PI3K) inhibitor BKM120 resulted in clinical activity in women with triple-negative breast cancer and those with high-grade serous ovarian cancer.
“Patients that had BRCA-mutant and BRCA wild-type tumors responded to the treatment.
“The results of this phase I trial were presented at a press briefing at the American Association for Cancer Research (AACR) Annual Meeting, held April 18 to 22 in Philadelphia.”
“Men with prostate cancer benefit from treatment with the pioneering drug olaparib – the first cancer drug to target inherited mutations – according to the results of a major trial presented today (Tuesday).
“Olaparib was licensed in December for women with ovarian cancer and inherited BRCA mutations, but the new research suggests it could also benefit men with genomic faults within their tumours.
“Researchers told the American Association of Cancer Research (AACR) conference in Philadelphia that up to 30 per cent of men with advanced prostate cancer had tumours with defects in repairing DNA – and these responded particularly well to olaparib.
“The men most likely to benefit could be identified by genetic testing to look for mutations in genes responsible for DNA repair – including the BRCA genes and the gene ATM.”
The gist: A drug called olaparib has shown promise for treating people with breast, prostate, ovarian, and pancreatic cancers. In a clinical trial with volunteer patients, olaparib was shown to shrink tumors or make them disappear in 26 percent of the patients. All patients involved had inherited BRCA1 or BRCA2 mutations.
“Olaparib, an experimental twice-daily oral cancer drug, produces an overall tumor response rate of 26 percent in several advanced cancers associated with BRCA1 and BRCA2 mutations, according to new research co-led by the Abramson Cancer Center of the University of Pennsylvania. The positive response provides new hope for patients with ovarian, breast, pancreatic and prostate cancers whose conditions have not responded to standard therapies. Results of the phase II study are available online in the current issue of the Journal of Clinical Oncology.
“For the majority of patients in the study, olaparib was at least their third different cancer therapy. Based on the new data, the authors say olaparib warrants further investigation in phase III trials. The positive response in metastatic pancreatic cancer patients who had received an average of two prior rounds of chemotherapy is an especially noteworthy finding since therapeutic options for these patients are limited.
“The international research team studied nearly 300 patients with inherited BRCA1 and BRCA2 mutations who had advanced cancers that were still growing despite standard treatments. Patients were enrolled and treated at 13 centers around the world. In addition to the 26 overall shrinkage or disappearance rate in tumors following treatment with olaparib, researchers also found no further growth in cancer for at least eight weeks in 42 percent of patients.”
“AstraZeneca’s new cancer drug olaparib, which won a green light from European regulators last month for inherited ovarian cancer, could also be used much more widely to treat prostate cancer, according to a leading oncologist.
“Johann de Bono, professor of experimental cancer therapeutics at the Institute of Cancer Research in London, told a conference on Tuesday the drug had produced “encouraging” preliminary results in clinical tests against prostate cancer.
“Olaparib works by blocking an enzyme involved in cell repair and is designed for patients with hereditary BRCA gene mutations, which are also found in breast and gastric cancer.
“While AstraZeneca believes the drug has the potential to sell $2 billion a year, the company has so far only talked about its promise in ovarian, breast and gastric cancer.
“However, de Bono told the National Cancer Research Institute that olaparib might also work in patients who have not inherited BRCA mutations but do carry mutations to DNA repair genes within their tumors.
To test the theory, de Bono and colleagues have assessed olaparib in advanced prostate cancer tests, including a mid-stage Phase II clinical trial, the first part of which has now closed.
“ ‘Although PARP inhibitors like olaparib have generally been trailed in women with inherited BRCA mutations, these exciting new trials could give them a whole other lease of life in advanced prostate cancer and other tumors with DNA repair mutations,’ de Bono said.
” ‘It is too early to say whether they will prove to be beneficial in prostate cancer but the initial results from our preliminary trials have been encouraging.’ “
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.”