Merck's Keytruda Extends Survival in Lung Cancer Study

“Merck & Co’s approved Keytruda lung cancer treatment provided superior overall survival to chemotherapy in a late-stage study of patients with advanced disease whose tumors produce a protein called PD-L1 associated with increased risk of the disease.

“The U.S. drugmaker on Monday said patients taking the approved 2 milligram dosage of Keytruda and those taking an experimental 10 milligram dose had longer overall survival compared with those taking docetaxel, a standard treatment for non small cell lung cancer (NSCLC), the most common form of lung cancer. Keytruda thereby met its main goal of the study.

“Patients whose tumors had especially high levels of PD-L1 also went longer without a progression of disease than those taking docetaxel, Merck said. Those whose tumors expressed PD-L1, but not at high levels, did not show such a statistically significant benefit in progression-free survival.”


Video: Dr. Kunz on Potential of Immunotherapy in Neuroendocrine Tumors

“Pamela L. Kunz, MD, assistant professor of Medicine (Oncology), Stanford University School of Medicine, discusses the potential of immunotherapy in the treatment of patients with neuroendocrine tumors (NETs).

“There are currently some clinical trials under development looking at immunotherapy in NETs both at Stanford University School of Medicine and University of Pennsylvania, Kunz explains. One phase I/II trial will examine the safety and efficacy of intratumoral injection of ipilimumab combined with an anti—PD-L1 agent in these patients.”

“It is possible that immunotherapy agents could be agnostic to disease sites, Kunz says. Though it was originally believed that PD-1/PD-L1 expression is a requirement to be a predictive biomarker, additional research could show that it may not be necessary.”

Click through to watch the video.


FDA Approves Pembrolizumab for PD-L1-Positive Lung Cancer

“The FDA granted an accelerated approval to pembrolizumab (Keytruda) as a treatment for patients with pretreated advanced non­–small cell lung cancer (NSCLC) across all histologies whose tumors express PD-L1. The PD-1 inhibitor was approved along with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, and is indicated for patients who progressed on or after platinum-containing chemotherapy or EGFR-or ALK-targeted agents in patients harboring those mutations.

“The approval was based on data from the phase I KEYNOTE-001 trial, in which the overall response rate (ORR) with the drug was 41% among a subgroup of 61 patients with pretreated PD-L1­–positive advanced NSCLC as determined by the 22C3 pharmDx diagnostic test. Response duration ranged from 2.1 to 9.1 months. A survival improvement has yet to be demonstrated in a clinical trial, and the accelerated approval is contingent upon the eventual outcomes of confirmatory studies.”


Nivolumab Improves the Proportion of Lung Cancer Patients Alive After More than a Year

“Patients with a type of lung cancer called non-squamous non-small cell lung cancer (non-SQ NSCLC) have limited treatment options and a dismal prognosis once their disease has advanced and initial treatment with platinum-based chemotherapy has failed. Second-line treatment is usually with another chemotherapy drug, such as docetaxel or pemetrexed.

“Recent results have shown that the drug, nivolumab, improves survival for these and now updated results from the CheckMate 057 phase III clinical trial, to be reported at the 2015 European Cancer Congress today (Monday) with simultaneous publication of the study results in the New England Journal of Medicine, show that nivolumab continues to show an overall survival benefit compared to . Among patients randomised to receive nivolumab, significantly more were alive at 12 months compared to those treated with docetaxel – 51% versus 39% respectively – and a difference in survival remains at 18 months – 39% for nivolumab versus 23% for docetaxel.

“This improvement in survival was observed for all patients included in the trial, but nivolumab was more effective in patients whose tumours expressed a protein called programmed death ligand 1 (PD-L1), which plays a role in the immune system’s ability to recognise and attack tumours and has been correlated with response to immune checkpoint inhibitors such as nivolumab.”


Nivolumab and Ipilimumab Combination Active as First-Line Therapy for Advanced NSCLC

“Nivolumab (Opdivo) and ipilimumab (Yervoy), a chemotherapy-free regimen, showed activity as a first-line therapy for patients who have advanced non-small cell lung cancer (NSCLC), according to a preliminary clinical trial that was presented at this year’s World Conference on Lung Cancer.

“Four different regimens of nivolumab, the PD-1 inhibitor, and ipilimumab, the anti-CTLA-4 antibody, led to response rates of 13% to 39% in 148 patients with no prior exposure to systemic therapy. The combination produced deep and durable responses, with a low rate of treatment-emergent grade 3/4 adverse events (AEs) leading to discontinuation.

“ ‘Clinical activity was observed regardless of tumor PD-L1 expression,’ said lead investigator Naiyer A. Rizvi, MD, director of Thoracic Oncology and Immunotherapeutics at Columbia University Medical Center. ‘We have preliminary evidence of greater activity in tumors that have 1% or greater PD-L1 expression. The median disease control rate [response plus stable disease] was not reached in any arm, regardless of PD-L1 expression.’ “


To PD-L1 or Not to PD-L1: That Is the Question


These days, it seems that I write mostly about immune checkpoint blockade drugs, or some other new immunotherapy treatment for cancer. This post is no different—it covers PD-L1, a protein that is at the center of clinical decisions for selecting patients who are likely to benefit from treatment with an anti-PD-1 or anti-PD-L1 drug. Continue reading…


Immune Therapy Tops Chemo in NSCLC

“Patients with previously treated advanced or metastatic squamous non-small cell lung cancer (NSCLC) had improved survival with an immunotherapeutic drug than with chemotherapy, according to updated results from a randomized trial.

“Twice as many patients treated with nivolumab (Opdivo) remained alive at 18 months as compared with those treated with docetaxel, and six times as many patients were alive without progression at 18 months with nivolumab as compared with the chemotherapy standard for NSCLC.

“Median overall survival was 9.2 months with nivolumab and 6.0 months with docetaxel, Karen Reckamp, MD, of City of Hope National Medical Center in Duarte, Calif., reported here at the World Conference on Lung Cancer.”


FDA Grants Nivolumab Priority Review in Nonsquamous NSCLC

“Nivolumab (Opdivo) has received an FDA priority review designation for patients with previously treated nonsquamous non­–small cell lung cancer (NSCLC), according to the developer of the PD-1 inhibitor, Bristol-Myers Squibb (BMS). Under the expedited process, the FDA’s decision deadline is January 2, 2016.

“The FDA simultaneously granted nivolumab a breakthrough therapy designation in this setting. The priority and breakthrough designations are based on data from the phase III CheckMate-057 trial, in which second-line nivolumab reduced the risk of death by 27% versus docetaxel in patients with nonsquamous NSCLC, including a 60% risk reduction among patients with the highest levels of PD-L1 expression.

“Nivolumab was previously approved in March 2015 for patients with squamous cell NSCLC who have progressed on or after platinum-based chemotherapy.”


Pivotal Phase II Study Showed Roche's Investigational Immunotherapy Atezolizumab Shrank Tumours in People with a Specific Type of Lung Cancer

“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that in the large pivotal Phase II study, BIRCH, the investigational cancer immunotherapy atezolizumab (MPDL3280A; anti-PDL1) met its primary endpoint and shrank tumours (objective response rate; ORR) in people with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease expressed PD-L1 (Programmed Death Ligand-1). The study showed the amount of PD-L1 expressed by a person’s cancer correlated with their response to the medicine. Adverse events were consistent with what has been previously observed for atezolizumab.

“ ‘We are encouraged by the number of people who responded to atezolizumab and maintained their response during the study, which is particularly meaningful for people who had received several prior treatments,’ said Sandra Horning, M.D., Chief Medical Officer and head of Global Product Development. ‘We plan to present results at an upcoming medical meeting and will discuss these data as well as results from our other lung cancer studies with health authorities to bring this medicine to patients as quickly as possible.’ “