“A combination of two drugs delays progression of advanced, aggressive breast cancer by an average of nine months – working in all subsets of the most common type of breast cancer.
“The combination – of a first-in-class targeted drug called palbociclib, and the hormone drug fulvestrant – slowed cancer growth in around two-thirds of women with advanced forms of the most common type of breast cancer.
“The combination allowed many women with metastatic hormone-receptor-positive, HER2-negative cancer to delay the start of chemotherapy, which is the traditional treatment option in these patients once hormone drugs have stopped working.”
“Men who went on cholesterol-lowering statin drugs when they began androgen deprivation therapy for prostate cancer had a longer time in which their disease was under control than did men who didn’t take statins, a clinical trial led by Dana-Farber Cancer Institute investigators shows.
“In a study published online today by JAMA Oncology, the researchers report that men who had been taking statins since the start of androgen deprivation therapy (ADT) went a median of 27.5 months before their disease began to worsen, compared to 17.4 months for men who didn’t take statins. The trial involved 926 patients, 70 percent of whom had their disease progress during a six-year period.
“ ‘This median 10-month benefit in delaying disease progression suggests that statins could be a valuable addition to our current therapies for prostate cancer,’ says the study’s first author, Lauren Harshman, MD, medical oncologist at the Lank Center for Genitourinary Oncology at Dana-Farber. ‘These results are supported by multiple prior epidemiologic studies demonstrating that statin use may be associated with improved outcomes in prostate cancer, but require validation.’ “
“Two new drugs for a specific lung cancer scenario are approaching the market –― AZD9291 (AstraZeneca Pharmaceuticals LP) and rociletinib (Clovis Oncology), and both companies are preparing to file for approval.
“Both drugs are third-generation EGFR inhibitors destined for use in patients who have non–small cell lung cancer (NSCLC) that is EGFR-mutation-positive and has responded to treatment with first-line EGFR inhibitors, but is now progressing.
“In about 60% of these cases, the disease is progressing because the tumor has developed a new mutation, known as EGFR T790M. This mutation confers resistance to treatment with first- generation EGFR inhibitors, such as erlotinib (Tarceva, Osi Pharmaceuticals, Inc) and gefitinib (Iressa, AstraZeneca Pharmaceuticals LP) or the second-generation EGFR inhibitor afatinib (Gilotrif, Boehringer Ingelheim Pharmaceuticals, Inc).”
“More patients with advanced melanoma who had progressed on ipilimumab with or without a BRAF inhibitor were able to achieve an objective response when treated with the PD-1 immune checkpoint inhibitor nivolumab than with alternative chemotherapy options, according to the interim analysis results of the CheckMate 037 trial published recently in Lancet Oncology.
“In fact, the rate of objective response was about threefold greater with nivolumab compared with investigator’s choice of chemotherapy; however, no difference in progression-free survival in the intention-to-treat population was noted.
“These results were the basis of the December 2014 US Food and Drug Administration accelerated approval of nivolumab for this patient population.
“ ‘Findings from our study show that nivolumab leads to clinically meaningful improvements in the proportion of patients achieving an objective response and provide a manageable safety profile when compared with chemotherapy,’ wrote Jeffrey S. Weber, MD, of Moffitt Cancer Center, Tampa, Florida, and colleagues. ‘Nivolumab can now be considered as a new treatment option for patients that have progressed after ipilimumab, or a BRAF inhibitor and ipilimumab if their melanoma is BRAF V600–mutated.’ ”
“Immunomedics, Inc., (Nasdaq:IMMU) today announced that 33% of patients with small cell lung cancer (SCLC) and 31% with non-small cell lung cancer (NSCLC) had their tumor reduced in size by 30% or more, after being treated with sacituzumab govitecan, the Company’s lead investigational antibody-drug conjugate (ADC). Including patients that reported stable disease as their best response, the ADC controls the progression of the cancer in 75% and 56% of NSCLC and SCLC patients, respectively. These patients had either failed to respond to their last lung cancer therapies or their cancer had returned or progressed.
“Dr. Francois Wilhelm, Chief Medical Officer, presented the updated results at the 15th Annual Targeted Therapies of Lung Cancer Meeting, an invitation-only meeting sponsored by The International Association for the Study of Lung Cancer (IASLC).
“Sacituzumab govitecan is a next generation ADC designed for targeted therapy of solid cancers. The agent was created by site-specifically conjugating a TROP-2-targeting antibody with a high ratio of a moderately toxic drug, SN-38, using a pH sensitive linker. TROP-2 is a receptor found on many human cancer cells, such as cancers of the breast, cervix, colon and rectum, kidney, liver, lung, ovary, pancreas, and prostate, but with only limited expression in normal human tissues. In an animal model of human pancreatic cancer, the ADC delivered up to 135-times the amount of SN-38 to the tumor than when irinotecan, the parent drug of SN-38, was given.”
“Tasquinimod prolonged survival in men with minimally symptomatic, metastatic castration-resistant prostate cancer compared with placebo, according to results of a randomized, phase 2 study. Results suggest the survival advantage was particularly apparent among men with skeletal metastases. The study included 201 men. Researchers assigned 134 of them to tasquinimod (Active Biotech), an oral immunomodulatory, anti-angiogenic and anti-metastatic novel agent. The other 67 men were assigned placebo; however, 41 of them crossed over to treatment with tasquinimod during the study.”
“Adding a spinal or epidural painkiller to general anesthesia during prostatectomy may benefit long-term patient outcomes, according to a large retrospective study. Researchers at the Mayo Clinic in Rochester, Minnesota, and colleagues analyzed medical records and patient outcomes over a median of 9 years. After adjusting for comorbidities and factors such as positive surgical margins, and adjuvant hormonal and radiation therapies within 90 postoperative days, the analysis found that general anesthesia alone, but not the combination of general anesthesia plus a localized painkiller, was associated with an increased risk of systemic prostate cancer progression (hazard ratio [HR] = 2.81, P = .008) and a higher overall mortality (HR = 1.32, P = .047). Prostate cancer deaths were also higher, but this outcome was not statistically significant (HR = 2.2, P = .091).”
“University of California, Los Angeles (UCLA) researchers have discovered how prostate cancer stem cells evolve as the disease progresses, a finding that could help point the way to more highly targeted therapies. Following recent studies showing that prostate cancer originates in basal stem cells, UCLA researchers were surprised to discover that the cancer eventually begins to grow from a different type of cell called a luminal stem cell. The new discovery indicates that the basal stem cells evolve into luminal stem cells as the cancer grows. Existing prostate cancer drugs are designed to seek out and kill the basal stem cells that give rise to the cancer, so the evolution from basal to luminal stem cells creates a ‘moving target’ that renders the drugs less effective over time.”
Haffner MC, Mosbruger T, Esopi DM, Fedor H, et al. The Journal of Clinical Investigation. Oct 25, 2013.
“Recent controversies surrounding prostate cancer overtreatment emphasize the critical need to delineate the molecular features associated with progression to lethal metastatic disease. Here, we have used whole-genome sequencing and molecular pathological analyses to characterize the lethal cell clone in a patient who died of prostate cancer. We tracked the evolution of the lethal cell clone from the primary cancer to metastases through samples collected during disease progression and at the time of death. Surprisingly, these analyses revealed that the lethal clone arose from a small, relatively low-grade cancer focus in the primary tumor, and not from the bulk, higher-grade primary cancer or from a lymph node metastasis resected at prostatectomy. Despite being limited to one case, these findings highlight the potential importance of developing and implementing molecular prognostic and predictive markers, such as alterations of tumor suppressor proteins PTEN or p53, to augment current pathological evaluation and delineate clonal heterogeneity. Furthermore, this case illustrates the potential need in precision medicine to longitudinally sample metastatic lesions to capture the evolving constellation of alterations during progression. Similar comprehensive studies of additional prostate cancer cases are warranted to understand the extent to which these issues may challenge prostate cancer clinical management.”