“President Jimmy Carter’s battle with metastatic melanoma to the brain has placed increased attention on management of this disease. President Carter was treated with focused stereotactic radiation to the brain and anti-PD-1 therapy. Researchers at Moffitt Cancer Center recently reported the first series of patients treated with this combined modality approach. They found that radiation therapy combined with the immune-targeting drug nivolumab in melanoma patients with brain metastases is safe and improves their survival compared to historical data.
“Nivolumab is a therapeutic agent that targets a protein on immune cells called PD-1. Binding of PD-1 to its ligand PD-L1, which is found on tumor cells, causes immune cells to decrease their activity and allows cancer cells to escape immune detection and cell death. Nivolumab blocks the PD-1/PD-L1 interaction and restimulates the body’s own immune system to target tumor cells. Nivolumab has been approved by the Food and Drug Administration to treat advanced non-small cell lung cancer, renal cell carcinoma, and melanoma; however, the impact of nivolumab on brain metastases is unclear.”
“The surface has only been scratched in the investigation of radiation and immunotherapy in combination for the treatment of patients with prostate cancer, says Steven Finkelstein, MD, of 21st Century Oncology.
“ ‘There is so much undiscovered territory with respect to this research. The fact there that are only a few clinical trails now of any significance in this area means that we need to do more work,’ says Finkelstein, a Scottsdale board certified radiation oncologist, adjunct associate professor at Translational Genomic Research Institute, and executive director of the Arizona Cancer Research Alliance. ‘I’ve spent a career working on this topic, and only now, after 20 years, are we starting to make progress.’
“While progress has been slow, the outlook is bright for the use of immunotherapy and radiation together in prostate cancer, says Finkelstein. He is currently working on a multicenter trial, which is investigating the effects of radiation therapy to augment anti-tumor responses from immunotherapy with sipuleucel-T (Provenge).”
“Data collected in Japanese and Korean patients included in the global PALOMA3 trial provides evidence that combining palbociclib with fulvestrant is an effective strategy to overcome endocrine resistance in women with hormone receptor positive (HR+), HER2 negative (HER2-) advanced breast cancer. The analysis of efficacy and safety of the combined therapy in an Asian population will be presented (1) at the first ESMO Asia 2015 Congress in Singapore, and results are in line with those reported in all patients (both Asian and non-Asian) earlier this year.
“Endocrine resistance is a major clinical issue that makes advanced breast cancer more difficult to treat. Hormone therapy is generally well tolerated and an easy-to-administer option for breast cancer, with demonstrated benefits in patients whose tumours express hormone receptors (HR), particularly the HR+/HER2- subgroup. The ideal option for patients is to be on one endocrine therapy after another, as long as the disease responds or remains unchanged. ‘However, unavoidably, resistance develops in almost all advanced patients a median ten months after the first-line hormonal agent is administered, and a much shorter median time after the second- or third-line hormonal agents, eventually driving patients to switch to the more toxic chemotherapy,’ one of the study authors, Dr. Jungsil Ro, Center for Breast Cancer at the National Cancer Center, Goyang, Korea, said.”
“Swiss drugmaker Roche released on Monday what it called encouraging early data on cancer drug atezolizumab in combination therapy for treating a form of advanced melanoma.
“A phase Ib study of atezolizumab (MPDL3280A), used in combination with the BRAF inhibitor Zelboraf for previously untreated BRAFV600 mutation-positive inoperable or metastatic melanoma, showed adverse events were “manageable and generally reversible”, it said.
“It showed the combination resulted in an objective response rate of 76 percent of people, including three complete responders.”
“Dual HER2 blockade with trastuzumab and lapatinib was no better than trastuzumab alone in producing pathologic complete responses (pCR) in metastatic HER2-positive breast cancer patients in the neoadjuvant setting, according to a new study. Those with hormone receptor–negative disease did see an improvement with the dual blockade.
“ ‘In randomized neoadjuvant trials, dual HER2 targeting generally results in higher pCR rates, but the magnitude of this effect has varied,’ wrote study authors led by Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill. The new trial was a three-arm study of preoperative therapy in 305 patients with stage II/III HER2-positive breast cancer; 118 patients were randomized to paclitaxel along with trastuzumab and lapatinib, 120 to paclitaxel with trastuzumab alone, and another 67 to paclitaxel along with only lapatinib. That last trial arm was closed early. Results were published online ahead of print in the Journal of Clinical Oncology.”
“Oligometastatic prostate cancer is optimally treated with the combination of docetaxel and androgen deprivation therapy (ADT), according to a presentation at the 7th European Multidisciplinary Meeting on Urological Cancers (EMUC).
“ ‘Oligometastatic disease is a transit state of prostate cancer and is an imaging technique-dependent definition,’ Bertrand Tombal MD, PhD, Chairman of the Division of Urology, Universite Catholique de Louvain, Brussels, Belgium, explained at the conference. ‘Nevertheless, it is unlikely that metastases targeted treatment will be enough to control the disease.’ “
“The FDA has approved a combination of vemurafenib (Zelboraf) and cobimetinib (Cotellic) to treat patients with metastatic or unresectable BRAF V600E/K mutation-positive melanoma. The approval was based on based on an extension in progression-free survival (PFS) in the phase III coBRIM study.
“In the data submitted to the FDA, the median PFS with the combination was 12.3 versus 7.2 months with vemurafenib plus placebo (HR, 0.58; 95% CI, 0.46-0.72). PFS was the primary endpoint of the study with secondary outcome measures including overall survival (OS), objective response rate (ORR), duration of response, and safety.”
“Adding the investigational anticancer therapeutic tivantinib to standard erlotinib treatment substantially increased progression-free survival for patients with advanced nonsquamous non–small cell lung cancer (NSCLC) who had tumors positive for epidermal growth factor receptor (EGFR) gene mutations, according to a subset analysis of data from the phase III MARQUEE clinical trial presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Nov. 5–9.
” ‘EGFR inhibitors like erlotinib are effective treatments for patients with advanced NSCLC with and without EGFR mutations,’ said Wallace Akerley, MD, director of thoracic oncology at the Huntsman Cancer Institute at the University of Utah in Salt Lake City. ‘However, tumors invariably develop resistance. MET overexpression is associated with resistance to EGFR therapy, and the phase III MARQUEE clinical trial set out to investigate whether adding the MET inhibitor tivantinib to erlotinib treatment could improve patient outcomes.’ “
“Combinations of targeted therapies continue to advance toward full regulatory approval for patients with metastatic or unresected melanoma, given the substantial benefits seen with these agents. At this time, the FDA is considering two applications for separate combinations of BRAF and MEK inhibiting agents for patients with unresectable or metastatic BRAFV600 mutation-positive melanoma.
“ ‘The future of the treatment of melanoma is clearly going to be in combinations, both for targeted therapy and for immunotherapy,’ said Jeffrey S. Weber, MD, PhD, who recently joined the NYU Langone Medical Center. ‘Already, there is an FDA-approved combination therapy that is targeted; that is dabrafenib and trametinib. There are new combinations coming up, mainly concerning CDK 4/6 and MEK inhibitors in NRAS-mutated but BRAF wild-type melanoma, which is an unmet medical need.’ “