UPDATE 1-Novartis Works with Bristol-Myers Squibb to Test Lung Cancer Drugs

The gist: Combining existing drugs can sometimes result in new, more effective cancer treatments. As we posted on our Need to Know blog today, lung cancer researchers are testing drug combinations that involve immunotherapies—treatments that boost the immune system to fight cancer. Now, two drug companies have announced that they will be testing combinations of their lung cancer drugs. An immunotherapy drug called Opdivo will be combined with targeted drugs. The combinations will be tested in clinical trials with volunteer patients who have late-stage non-small cell lung cancer (NSCLC). It is hoped that the combinations will work better than any of the drugs alone.

“Swiss pharma group Novartis AG said on Monday it would work with Bristol-Myers Squibb Co to test the U.S. drugmaker’s immuno-oncology drug Opdivo in combination with three of its own experimental lung cancer drugs.

“The clinical collaboration will help Novartis advance its efforts in the field of immunotherapy, one of the hottest areas in biotech right now, following the acquisition of CoStim Pharmaceuticals Inc this year, the drugmaker said.

“Novartis currently lags rivals such as Roche, Merck , AstraZeneca and Bristol-Myers in the race to develop immunotherapies – drugs that fight cancer by harnessing the body’s immune system.

“The two companies will test the combination of three molecularly targeted compounds with Bristol-Myers’ investigational PD-1 immune checkpoint inhibitor Opdivo (nivolumab) in phase I and II studies, Novartis said, adding it would conduct both studies.

” ‘Preclinical data suggests that combining molecularly targeted agents with immunotherapies such as nivolumab may have synergistic effects and lead to better outcomes for patients,’ Alessandro Riva, global head of Novartis oncology development and medical affairs, said in the statement.”


Immune System-Boosting Drugs, New and Old, Are Explored in Combination Treatments for Lung Cancer


Readers of this blog will already know a thing or two about immunotherapy (immune system-activating drugs) and targeted therapy in lung cancer. Both approaches have benefited many patients in recent years. Now, research is being done to combine immunotherapies with other types of drugs. Of particular interest are immunotherapies that target PD-1, PD-L1, and CTLA4. These drugs, also known as immune checkpoint antibodies, are being tested in combination with other drugs in patients participating in the clinical trials below. Continue reading…


New Standard in Melanoma: Combo of BRAF and MEK Inhibitors

The gist: Two new, similar melanoma treatments have been tested in clinical trials—research studies with volunteer patients. Both of the trials are focused on people with advanced melanoma whose tumors have mutations in the BRAF gene. Such patients are often treated with a targeted therapy called a BRAF inhibitor, but their tumors often become resistant and keep growing. In these two trials, the researchers hope that combining BRAF inhibitors with other targeted drugs known as MEK inhibitors might help patients avoid resistance. One of the trials tested a combination of the drugs vemurafenib and cobimetinib. The other trial combined dabrafenib and trametinib. In both trials, patients treated with the combination treatment fared better than patients treated with just a BRAF inhibitor alone.

“For patients with advanced melanoma that isBRAF-mutation positive, the combination of a BRAF and MEK inhibitor works better than a BRAF inhibitor alone. The data come from 2 phase 3 trials presented here at the presidential session of the European Society for Medical Oncology (ESMO) Congress 2014.

“Experts here say that such combinations should be the new standard of care in this patient population, which accounts for about 40% of all melanoma.

“At present, the first-line treatment for these patients is a BRAF inhibitor used alone, but while these drugs can elicit dramatic responses, they do not last, and after about 5 or 6 months, patients relapse. The tumor develops resistance to the drug via the MAPK pathway, and this is blocked by a MEK inhibitor. Adding a MEK inhibitor to the BRAF inhibitor from the beginning of treatment blocks this resistance pathway and improves outcomes.

“The 2 new trials are known as COMBI-v and coBRIM.

“Both studies used vemurafenib (Zelboraf, Roche/Plexxikon) as the single BRAF inhibitor, but each used a different combination of BRAF and MEK inhibitor.”


Roche Drugs Shown Effective in Breast and Skin Cancers

The gist: Drug company giant Roche is mixing drugs in new combinations to provide melanoma and breast cancer patients with potential new treatments. This article outlines the company’s endeavors.

“Mixing drugs in various combinations has given Roche Holding AG (ROG) effective new treatments for skin and breast cancer strains.

“Combining Zelboraf, a melanoma drug now on the market, with experimental cobimetinib showed significant improvement over Zelboraf alone, according to data presented today at the European Society for Medical Oncology’s annual meeting in Madrid.

“Roche said yesterday that a combination of two breast cancer drugs, plus chemotherapy, could add almost 16 months to the lives of a class of patients. Roche today also reported data from an early-stage study of its MPDL3280A immune therapy treatment in bladder cancer which showed a 52 percent response rate. If successfully developed, the drug will be the first new treatment for bladder cancer in 30 years, the Basel, Switzerland-based company said.

“ ‘This is a good meeting for Roche,’ said Asthika Goonewardene, an analyst with Bloomberg Intelligence. ‘They’re firing in three different areas.'”


ESMO 2014 Press Release: New Data on Combination Treatments for Melanoma

The gist: Researchers tested a new melanoma treatment in a clinical trial—a research study with volunteer patients. The treatment combines the targeted drugs vemurafenib and cobimetinib. All of the patients who participated in the trial had melanoma tumors with mutations in the BRAF gene, as detected by molecular testing. The combination treatment proved more beneficial for these patients than vemurafenib alone.

“Combination therapy with both BRAF inhibitor vemurafenib and MEK inhibitor cobimetinib achieves greater progression-free survival and response rates than vemurafenib plus placebo in BRAF-mutation positive melanoma, according to phase III data presented at the ESMO 2014 Congress in Madrid, Spain.

“ ‘Before the results of this study, we knew that cobimetinib plus vemurafenib could be safely delivered together with highly promising rates of tumour shrinkage; however until the performance of a scientifically rigorous randomised trial the potential magnitude of this benefit could not be measured,’ says lead author Dr Grant McArthur, head of the Cancer Therapeutics Program at the Peter MacCallum Cancer Centre, Melbourne, Australia.

“The ongoing CoBRIM study enrolled 495 treatment-naive patients with BRAFV600-mutation-positive unresectable locally advanced or metastatic melanoma. Patients were randomised to received a 28-day treatment cycle of vemurafenib (960 mg, twice daily), and either cobimetinib or placebo (60 mg daily from days 1-21), with a primary end-point of progression-free survival.

“Patients in the combination arm of the study showed a significantly improved median progression-free survival of 9.9 months, compared to 6.2 months in the placebo arm, and a 49% reduction in the risk of progression. Researchers observed a response rate of 68% in the combination arm and 45% in the control arm, including a complete response in 10% of patients treated with combination therapy compared to 4% of patients treated with vemurafenib alone.”


Puma Biotechnology Cancer Drug Shows Positive Mid-Stage Results

The gist: Researchers tested a new lung cancer treatment in a clinical trial—a research study with volunteer patients. The treatment combines the drugs PB272  and temsirolimus. The results were modest; patients who took the combo experienced about four months without their cancer worsening, while patients who took only PB272 went for three months without worsening.

“Puma Biotechnology Inc said its experimental lung cancer drug was safe to be administered with an already approved treatment for the disease in a mid-stage study.

“The time where a patient’s disease did not progress increased to four months when given a combination of Puma’s PB272 and temsirolimus, compared to about three months when given only PB272, according to data from the study.

“All the patients in the study were given a high dose of the drug loperamide to prevent diarrhea related to PB272.

“There were no severe diarrhea events seen in the trial, the company said.”


Failed Cancer Vaccines Might Live Again with New Immune Drugs

“Using vaccines to fight cancer is a field littered with failures but experts believe it is possible the approach could get a new lease of life if such shots are combined with a new class of drugs called checkpoint inhibitors.

“Unlike traditional preventative vaccines, therapeutic cancer vaccines are designed for people with established disease and are supposed to boost the patient’s immune system to keep tumors at bay.

“Unfortunately, the theory has not worked out in practice because, while the vaccines are successful at triggering a response from the ‘foot soldiers’ of the immune system, cancer cells still manage to escape detection.

“The result has been a series of failures with high-profile experimental cancer vaccines such as Merck KGaA’s Stimuvax and GlaxoSmithKline’s MAGE-A3.

“GSK threw in the towel on its vaccine in April, dashing hopes for a project that was once seen as a potential multibillion-dollar sales opportunity in lung cancer and melanoma.”


Targeted Combination Therapy Halts Disease, Extends Life in Advanced Melanoma Patients

The gist: Researchers tested a new melanoma treatment in a clinical trial—a research study with volunteer patients. The treatment combines the targeted drugs dabrafenib and trametinib. All of the patients who participated in the trial had inoperable stage IIIC or stage IV melanoma. Also, each patient’s tumors had one of two particular mutations in the BRAF gene, known as V600E and V600K. In the trial, patients who were treated with the combination therapy had significantly lower chances of their cancer worsening and lower chances of death.

“A world-first study in today’s New England Journal of Medicine heralds the efficacy of a targeted combination drug therapy after reporting major declines in the risk of disease progression and death in people with metastatic melanoma.

“The multi-centre, double-blind, randomised, phase 3 trial compared oral dabrafenib (150 mg twice daily) and oral trametinib (2 mg once daily) combination therapy with oral dabrafenib (150 mg twice daily) and placebo.

“All trial patients had inoperable stage 3C or 4 metastatic melanoma that had a BRAF gene mutation V600E or V600K. Among cancer patients with metastatic melanoma, about 40 per cent have a BRAF gene mutation – an abnormality that assists some melanoma tumours to grow and spread.

“Led by Associate Professor Georgina Long of Melanoma Institute Australia at the University of Sydney, the finding affirms accumulating evidence of the efficacy of targeted combination therapies in extending life and halting disease progression in patients with cancers that carry genetic mutations that resist monotherapies.”


Calming Down Immune Cells Could Hold Key to Melanoma Treatment

The gist: New research has shed light on why some patients’ melanoma tumors resist standard treatment. The scientists found that certain immune system cells produce chemical signals that may protect melanoma cells, and keep them from being destroyed. To get around this, the researchers say, drugs that affect the immune system (immunotherapy) could be combined with standard melanoma treatment. Indeed, such a combination is already being tested in a clinical trial—a research study with volunteer patients.

“Immune cells may be responsible for drug resistance in melanoma patients, according to research published in Cancer Discovery.”Cancer Research UK scientists at The University of Manchester found that chemical signals produced by a type of immune cell, called macrophages, also act as a survival signal for .

“When the researchers blocked the macrophages’ ability to make this signal – called TNF alpha – melanoma tumours were much smaller and easier to treat.

“When melanoma patients are given chemotherapy or radiotherapy it causes inflammation, increasing the number of macrophages in the body – and raising the levels of TNF alpha. This research suggests that targeting this chemical ‘survival signal’ could lead to new ways to treat the disease.”