Bristol's Opdivo Reduces Risk of Death from Common Lung Cancer

“Chicago May 29 Bristol-Myers Squibb Co’s drug, Opdivo, improved survival for patients with the most common form of lung cancer, nearly doubling survival for those with high levels of a specific protein in their tumors compared with chemotherapy, according to clinical trial results presented on Friday.

“The trial found that Opdivo, part of a new class of drugs that harness the immune system to fight cancer, reduced by 27 percent the risk of death from advanced non-squamous non-small cell lung cancer (NSCLC), compared with chemotherapy. The benefit reached 60 percent for patients with the highest levels of the PD-L1 protein.

“The Bristol drug was approved by U.S. regulators in December to treat advanced melanoma and competes with Keytruda from Merck & Co Inc. Investors have been keeping a close eye on Opdivo’s performance in lung cancer, the most common form of the disease worldwide, and a far larger market. Opdivo was cleared in March to treat the less-common squamous type of NSCLC. Between 85 percent and 90 percent of all lung cancers are NSCLC, and more than two-thirds of those are the non-squamous type, according to the American Cancer Society.”


New Class of Drugs Shows More Promise in Treating Cancer

“A new drug that unleashes the body’s immune system to attack tumors can prolong the lives of people with the most common form of lung cancer, doctors reported on Friday, the latest example of the significant results being achieved by this new class of medicines.

“In a separate study, researchers said they had found that a particular genetic signature in the tumor can help predict which patients could benefit from the immune-boosting drugs.

“The finding could potentially extend use of these drugs to some patients with colorectal cancer, prostate cancer and other tumors that have seemed almost impervious to the new drugs. Most of the substantial results so far with these expensive drugs have been in treating melanoma and lung cancer.

“ ‘If you have the signature, you should treat with these checkpoint inhibitors,’ Dr. Luis A. Diaz Jr., an associate professor of oncology at Johns Hopkins University and the senior author of the study on the genetic marker, said in an interview, referring to the new drugs.”


AstraZeneca and Lilly to Collaborate on Immuno-Oncology Combination Clinical Trial in Solid Tumours

“AstraZeneca and Eli Lilly and Company (Lilly) today announced that they have entered into a clinical trial collaboration to evaluate the safety and preliminary efficacy of AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with ramucirumab (CYRAMZA®), Lilly’s VEGF Receptor 2 antiangiogenic cancer medicine. The planned study will assess the combination as a treatment for patients with advanced solid tumours.

“The Phase I study is expected to establish the safety and a recommended dosing regimen, with the potential to open expansion cohorts in various tumours of interest, for the combination of MEDI4736 and ramucirumab. Under the terms of the agreement, the trial will be sponsored by Lilly. Additional details of the collaboration, including tumour types to be studied and financial terms, were not disclosed.”


‘Immune Checkpoint’ Drugs Show New Promise for Treating Non-Small Cell Lung Cancer


It has become routine practice to prescribe targeted drugs to patients with metastatic non-small cell lung cancer (NSCLC), whose tumors harbor molecular alterations in EGFR, ALK, and ROS. However, the majority of patients with NSCLC have no targetable mutations and lack good treatment options. Enter immunotherapy drugs, specifically ‘immune checkpoint blockade antibodies,’ to which many refer simply as ‘anti-PD-1 drugs,’ or simply ‘PD-1 drugs.’ In this post, I provide some updates on the efficacy of anti-PD-1 and anti-PD-L1 drugs in lung cancer. Continue reading…


Roche: "MPDL3280A Doubled the Likelihood of Survival Compared with Chemotherapy in People with a Specific Type of Lung Cancer"

“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced interim results from a global, randomised Phase II study (POPLAR) in people with previously treated NSCLC. The study showed the investigational cancer immunotherapy MPDL3280A (anti-PDL1) doubled the likelihood of survival (overall survival [OS]; HR=0.47) in people whose cancer expressed the highest levels of PD-L1 (programmed death ligand-1) compared with docetaxel chemotherapy. An improvement in survival was also observed in people who had medium and high (HR=0.56) or any level of PD-L1 expression (HR=0.63), as characterised by a test being developed by Roche. MPDL3280A was generally well tolerated and adverse events were consistent with what has been previously reported for MPDL3280A in NSCLC. Updated results will be presented in an oral session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO).

“ ‘In our study of MPDL3280A in previously treated lung cancer, the amount of PD-L1 expressed by a person’s cancer correlated with improvement in survival,’ said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. ‘The goal of PD-L1 as a biomarker is to identify people most likely to experience improved overall survival with MPDL3280A alone and which people may be appropriate candidates for a combination of medicines.’ “


Immune Checkpoint Inhibitors in Melanoma: New Directions


The drugs pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2015, respectively. These two competing blockbuster drugs are already changing the outlook in metastatic melanoma, previously considered to be a fatal disease. Known as ‘immune checkpoint inhibitors,’ they work by releasing ‘brakes’ on a patient’s own immune system, freeing it to attack tumors. In the wake of their success, researchers are now taking immune checkpoint inhibition in new directions. Continue reading…


First PD-1 Inhibitor in Lung Cancer May Soon Be Approved

The gist: This Q&A with an oncologist gives a good overview of a promising immunotherapy for non-small cell lung cancer (NSCLC). Immunotherapies are treatments that boost a patient’s own immune system to fight cancer. Based on good clinical trial results, the U.S. Food and Drug Administration (FDA) might soon approve a drug called nivolumab (Opdivo) for certain lung cancer patients. If it’s approved, doctors could prescribe it for patients with advanced, squamous NSCLC who have already tried two other treatments. Opdivo is a specific kind of immunotherapy called a PD-1 inhibitor.

“Immune checkpoint inhibitors targeted against PD-1 and its ligand PD-L1 have rapidly advanced as treatments for patients with melanoma and non–small cell lung cancer (NSCLC), following their initial debut in 2012.

“In the past 4 months alone, the PD-1 inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) have each gained separate approvals as treatments for patients with advanced melanoma. Additionally, in mid-January, phase III findings from the CheckMate-017 study demonstrated that nivolumab extended overall survival compared with docetaxel in patients with pretreated squamous cell NSCLC.

“Based on these findings and those from phase II studies, Bristol-Myers Squibb (BMS) is currently in the process of submitting a New Drug Application to the FDA for nivolumab as a third-line treatment for patients with squamous cell NSCLC. Furthermore, several phase III studies are currently examining the agent across a variety of tumor types.”


Immune System-Boosting "Immune Checkpoint Inhibitors" Show Promise for Treating Many Kinds of Cancer

The gist: Drugs called “immune checkpoint inhibitors” have shown promise for patients with multiple types of cancer. Immune checkpoint inhibitors are a type of immunotherapy, meaning they boost a patient’s own immune system to fight cancer. Two particularly promising immune checkpoint inhibitor drugs are MPDL3280A and pembrolizumab.

“Treatment with an immune checkpoint inhibitor led to consistent responses across multiple types of cancer, particularly in patients with suppressed immune systems that appeared to be ‘reinvigorated’ by the therapy, investigators reported.

“Response rates of 20% to 25% were seen in patients with advanced cancers, including lung, kidney, and head and neck cancers, as well as melanoma. The overall response to the engineered antibody MPDL3280A increased to 46% in patients whose tumors exhibited overexpression of programmed death-ligand 1 (PD-L1), a protein associated with immune suppression in multiple types of cancer, as reported a research letter in Nature.

“The antitumor activity was encouraging, but the identification of markers predictive of response could prove to be equally important if not more so, according to Roy S. Herbst, MD, PhD, of the Yale Cancer Center.

” ‘The most compelling thing about the study is the fact that we worked to develop predictive markers for who responds and who doesn’t,’ Herbst told MedPage Today. ‘We can measure PD-L1 immunostaining in the immune infiltrate — not on the tumor cells but on the macrophages and the lymphocytes in the immune microenvironment.’ “


Early Trial of New Drug Shows Promise for Patients with Triple-Negative Breast Cancer

The gist: A drug called pembrolizumab (aka Keytruda or MK-3475) has shown promise for people with metastatic triple-negative breast cancer (TNBC) whose tumors have high levels of a protein called PD-L1.  It was recently tested in patients in a clinical trialPembrolizumab is already approved by the U.S. Food and Drug Administration (FDA) for treating melanoma. It is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. More research will determine just how well pembrolizumab might work for TNBC.

“In patients with metastatic triple-negative breast cancer—a disease with no approved targeted therapies—infusion of pembrolizumab produced durable responses in almost one out of five patients enrolled in a phase-Ib clinical trial, according to data presented Dec. 10, at the 2014 San Antonio Breast Cancer Symposium.

“The multi-center, non-randomized trial was designed to evaluate the safety, tolerability and antitumor activity of bi-weekly infusions of pembrolizumab (MK-3475, marketed as Keytruda®). The researchers enrolled 27 patients, aged 29 to 72 years, who had metastatic triple-negative breast cancer that either relapsed after treatment for early stage disease or progressed on therapy for advanced disease.

” ‘For this group of patients our treatment options are limited to chemotherapy,’ said study director Rita Nanda, MD, assistant professor of medicine and associate director of the breast medical oncology program at the University of Chicago.

“All patients in the study had triple-negative tumors with high levels of a protein called programmed death-ligand 1 (PD-L1). This protein can suppress the immune system’s efforts to eliminate cancer cells. Pembrolizumab is a monoclonal antibody designed to help reactivate a person’s own immune system to help fight the tumor.”