News Digest for February 2019

Posted on: 2019-02-28 10:40:28

February 1, 2019

Rhein shows potent efficacy against non-small-cell lung cancer through inhibiting the STAT3 pathway (here)

Tumors with More Mutations Respond Better to Immunotherapy, Study Suggests (here)

Pfizer today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending Vizimpro® (dacomitinib) 45 mg, as monotherapy, be granted marketing authorization in the European Union (EU) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations. The CHMP’s opinion will now be reviewed by the European Commission (EC). (here)

Dr. Padda on Overcoming Resistance to Osimertinib in EGFR+ NSCLC (here)

NGS-Based Lung Cancer Profiling Used Routinely by Heidelberg Research Team (here)

Hypertension as a predictive biomarker in patients with advanced non-small-cell lung cancer treated with apatinib (here)

Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer (here)

February 2, 2019

Antibody–Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non–small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade (here)

The European Medicine’s Agency Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the frontline combination of atezolizumab (Tecentriq), bevacizumab (Avastin), paclitaxel, and carboplatin for the first-line treatment of patients with metastatic, nonsquamous non–small cell lung cancer (NSCLC).  For patients with EGFR or ALK molecular abnormalities, the 4-drug regimen should be indicated only after progression on appropriate targeted therapies.  The recommendation is based on data from the phase III IMpower150 study. (here)

High MET copy number gain (CNG) as measured by fluorescence in situ hybridization (FISH) was not associated with response to tyrosine kinase inhibitor (TKI) therapy in TKI-naive patients with metastatic non-small cell lung cancer (NSCLC) characterized by an activating EGFR mutation unless MET amplification, defined as CNG greater than 5 and MET/centromeric portion of chromosome 7 (CEP7) ratios greater than 2, was present. (here)

Officials with the FDA have expanded the label of pemetrexed for injection (Alimta, Eli Lilly) in combination with pembrolizumab (Keytruda, Merck) and platinum chemotherapy, according to a press release. (here)

The Lung Cancer Master Protocol is undergoing a major expansion to include patients with all non-small cell lung cancers.  The trial previously tested treatments for people with advanced stage squamous cell lung cancer. The trial is now open to all types of advanced stage non-small cell lung cancers. NSCLC makes up about 85 percent of all lung cancer diagnoses in the U.S. (here)

February 3, 2019

An Overview, Current Challenges of Drug Resistance, and Targeting Metastasis Associated with Lung Cancer - Chitra Thakur (here)

February 5, 2019

Preexisting antibodies in patients with non-small cell lung cancer treated with nivolumab or pembrolizumab appeared associated with both clinical benefit and the development of immune-related adverse events, according to a study published in JAMA Oncology. (here)

A Phase 1b clinical trial of ADCT-301 (camidanlumab tesirine) in adult patients with locally advanced or metastatic solid tumors has dosed the first patient. Patient enrollment for this multicenter, open-label study (NCT03621982) is ongoing. Approximately 50 patients will be recruited. (Information about study locations and contacts available here.)  To be included, a patient needs to have either head and neck, non-small cell lung cancer, gastric and esophageal cancers, pancreatic, bladder, renal cell carcinoma, melanoma, triple negative breast cancer, or ovarian cancer. Eligible patients also must be refractory (resistant) or intolerant to existing therapies and have adequate organ function. (here)

Shared genetic marker offers new promise in targeting specific ovarian and lung cancers // Although much more common than SCCOHT, non-small cell lung cancer (NSCLC) can be very difficult to cure. "We extended the SCCOHT work to NSCLC as we realised about 10% of these common tumours also lack SMARCA4," explains Xue. (here)

GlaxoSmithKline is making another big play in cancer, signing a wide-ranging deal with Merck KGaA for M7824, an immuno-oncology drug that made a splash at last year’s ESMO meeting.  The global alliance gets off the ground with a 300 million euro payment to Merck from GSK to secure co-development and co-marketing rights to the bifunctional fusion protein immunotherapy, an anti-PD-L1/TGF beta trap in clinical trials for solid tumours including non-small cell lung cancer (NSCLC).  (here)

Apatinib, a novel VEGFR inhibitor plus docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR: a phase I trial (here)

February 6, 2019

Osimertinib (Tagrisso) has effectively overcome the T790M resistance mechanism associated with earlier-generation EGFR TKIs, but patients with EGFR-positive non–small cell lung cancer (NSCLC) are still experiencing disease progression on the third-generation drug, said Sukhmani Padda, MD. (here)

Corvus Pharmaceuticals, today announced the presentation of updated biomarker and clinical results from its two lead programs that target the adenosine pathway, CPI-444, an adenosine A2A receptor antagonist, and CPI-006, an anti-CD73 antibody. The data were presented by Stephen Willingham, Ph.D., Senior Scientist at Corvus, at the Immuno-Oncology 360° Conference in New York during the “Discovery & Preclinical Science Plenary” session, which focused on tumor microenvironment changing technologies, pegylated cytokines and additional discovery and preclinical data. (here)

February 7, 2019

First-line osimertinib compared favorably to standard-of-care epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated non-small cell lung cancer, sustaining clinical benefit beyond first progression, according to post-progression data from the randomized phase 3 FLAURA trial.  These results suggest that first-line osimertinib (Tagrisso, AstraZeneca) does not cause any biological changes or resistance to subsequent anticancer therapies that would cause more aggressive disease or rapid progression, according to the researchers. (here)

Reflecting on the past 20 years of advances in non–small cell lung cancer (NSCLC), I am struck by how long a period went by with so little progress. Of course, today NSCLC treatment is changing at a breakneck pace, with new advancements presented at seemingly every major meeting and newly approved drugs emerging multiple times per year. However, not that long ago, NSCLC treatment was anything but exciting, and it took a completely different way of thinking about this disease to make today’s advances happen. (here)

Lara Kujtan, MD, assistant professor at the University of Missouri–Kansas City School of Medicine, discusses frontline therapy for patients with EGFR-positive non–small cell lung cancer (NSCLC). (here)

Randomised phase 2 study of pembrolizumab plus CC-486 vs pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer.  (here)

February 8, 2019

"(W)e have doubled the size of our trial comparing Libtayo monotherapy to chemotherapy in PD-L1-high patients. Regarding combinations, we’ll be focusing our efforts in first-line treating and combination therapy of Libtayo with chemotherapy. The ongoing Phase III combination study is being augmented to enroll non-small cell lung cancer patients irrespective of histology and the levels of PD-L1 expression and to randomize to Libtayo plus chemotherapy or chemotherapy alone. Amazingly enough despite the years of effort in many pivotal trials there’s only one PD-1 or PD-L1 antibody approved as monotherapy in first-line metastatic non-small cell lung cancer (Keytruda). If our ongoing trials succeed, we have the potential to be the second." (here)

Older adults with advanced non-small cell lung cancer (NSCLC) may be particularly vulnerable to adverse events, therapy discontinuation, glucocorticoid rescue, and hospitalization during treatment with immune checkpoint inhibitors (ICIs), according to a recent study published in the Journal of the American Geriatrics Society. (here)

A “Trojan horse” drug which attacks tumour cells from within may offer new hope to cancer patients with few options left, researchers say.  The new treatment has generated promising results in people with six different cancer types including cervical, bladder, ovarian and lung, early trial results published in journal The Lancet Oncology show.  The drug – tisotumab vedotin (TV) – was tested on patients with advanced cancers which had stopped responding to standard treatments and caused some tumours to shrink or stop growing. (here)

February 9, 2019

The National Cancer Institute Cancer Therapy Evaluation Program approved the following clinical research studies for Feb 2019 (here)

The rapid advances in targeted therapies in non-small cell lung cancer (NSCLC) make the optimization and implementation of cytology specimens for molecular testing a priority. Up to 70% of patients with NSCLC are diagnosed at advanced stages and tissue biopsies often cannot be taken. Although cytology samples provide high-quality material for molecular testing, molecular cytopathology is not yet well known or widely used. (here)

Immune checkpoint inhibitor therapy appeared to be a safe, effective treatment for patients with advanced-stage cancer and HIV infection, according to a systematic review published in JAMA Oncology.  (here)

Janakiraman Subramanian, MD, a medical oncologist and director of thoracic oncology and director of the Center for Precision Medicine at St. Luke’s Cancer Institute, discusses the future of immunotherapy in non–small cell lung cancer (NSCLC). (here)

February 10, 2019

Facilitating Immunotherapy Drug Development.  Naiyer A. Rizvi, MD, an internationally recognized leader in the treatment of lung cancer and immunotherapy drug development, is Director of Thoracic Oncology and Immunotherapeutics in Medical Oncology at NewYork-Presbyterian/Columbia University College of Physicians and Surgeons. Dr. Rizvi’s research of antibodies that can reinvigorate T cells to recognize lung cancer cells as foreign and destroy the cancer cells has been a major development in thoracic oncology. (here)

February 11, 2019

Immunicum announced today that the first patient has been treated in the Phase Ib/II ILIAD clinical trial. The trial will evaluate the safety and efficacy of Immunicum's lead product in development, ilixadencel, in combination with checkpoint inhibitors (CPIs) in three cancer indications: head and neck cancer, non-small cell lung cancer and gastric cancer. The initial Phase Ib portion of the trial will be conducted at clinical centers in the United States. (here)

Helix BioPharma, an immuno-oncology company developing innovative drug candidates for the prevention and treatment of cancer, today provides an update on the Company’s strategic plans.  //  L-DOS47 clinical development program is focused solely on combination therapies in patients with non-small cell lung cancer (“NSCLC”).  (here)

February 12, 2019

A long-term analysis of the pivotal KEYNOTE-024 trial showed that pembrolizumab continues to improve survival and have less toxicity compared with platinum-based chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) that is positive for programmed death ligand 1 (PD-L1). The results were published in the Journal of Clinical Oncology. (here)

Penn Medicine Looks to Improve Outcomes for Solid Tumors With CAR-T (here)

February 13, 2019

There is a need for more data regarding immunotherapy options for the treatment of patients with EGFR-mutant lung cancer, with the strongest data to date coming from the phase III IMpower150 trial, explained Edward B. Garon, MD, during the 16thAnnual Winter Lung Cancer Conference. (here)

Early-Stage NSCLC Is Ripe for Change:  It is extremely disappointing that for the very population of early-stage patients for whom cure is most likely, and for whom the impact of novel therapies could be the most substantial, little has changed since the acceptance of adjuvant chemotherapy for resected stage IB-IIIA patients as the standard of care about 2 decades ago.  (here)

Understanding the molecular basis of lung cancer has allowed researchers to personalize patient treatment, but improving early detection methods and continuing to enhance the reach of immunotherapy will be crucial to further progress, said Heather Wakelee, MD.  While the future looks promising, Wakelee, an associate professor of medicine at Stanford University Medical Center, called for more extensive research to further extend survival for these patients.  In an interview with OncLive, Wakelee shared insight on the current landscape of lung cancer and discussed how immunotherapy and targeted therapy can be improved for patients with NSCLC.  (here)

Liquid biopsy is emerging as an important diagnostic and evaluative tool for oncologists in the treatment of non–small cell lung cancer (NSCLC), especially as a greater understanding of the tumor microenvironment emerges. In addition, multiple molecular biomarkers are undergoing evaluation, particularly circulating tumor DNA (ctDNA).  Bob T. Li, MD, MPH, explained ctDNA’s growing importance in lung cancer, given the disease’s challenging prognosis.  (here)

Cyclin-dependent kinase 4/6 (CDK4/6) inhibition, a treatment used with some breast cancers, might also prove effective against tumor suppressor SMARCA4 (BRG1) mutation-harboring lung cancers and a rare, aggressive form of SMARCA4 mutation-driven ovarian cancer, suggest preclinical findings reported in a pair of papers in Nature Communications. (here)

New therapies that inhibit EGFR and ALK gene rearrangements in non–small cell lung cancer (NSCLC) have changed the paradigm of care in these settings. However, their use has involved a frustrating game of one-upmanship, in which these tumors develop new resistance mechanisms that counter successive generations of inhibitors.  (here)

New assay selects patients with lung cancer for treatment with immune checkpoint inhibitors. // Molecular analysis of small, unfixed tissue samples collected using minimally invasive bronchoscopy can identify individuals with malignant disease and yield PD-L1 expression levels (here)

February 14, 2019

Advaxis, Inc.  (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, announced it has initiated its Phase 1/2 clinical trial to evaluate ADXS-503, part of the Company’s ADXS-HOT program, in the treatment of non-small cell lung cancer (NSCLC) and has enrolled the first patient in the trial. ADXS-HOT is a cancer-type specific immunotherapy program which leverages Advaxis’ proprietary Lm technology platform to target hotspot mutations that commonly occur in specific cancer types as well as other proprietary, tumor-associated antigens. To date, more than 10 drug candidates have been designed for different tumor types under the ADXS-HOT program. (here)

Assessing the level of programmed death ligand 1 (PD-L1) expressed by a non–small-cell lung (NSCLC) tumor can help clinicians determine how the patient should be treated.  Now, researchers report a novel and rapid approach for quantifying PD-L1 expression levels in tumors that requires only small amounts of tissue that can be collected using minimally-invasive bronchoscopy techniques. This technique can also be used to discriminate malignant from benign tumors and identify mutational status, all of which can guide and refine therapeutic decisions.  (here)

Clinical value of neutrophil-to-lymphocyte ratio in patients with non-small-cell lung cancer treated with PD-1/PD-L1 inhibitors (here)

February 15, 2019

An Exome-Based Model to Predict Benefit of ICIs in NSCLC.  Results from a retrospective analysis of the exome sequences of tumor and blood specimens from patients with metastatic non-small cell lung cancer (NSCLC) who had been enrolled in a clinical trial of single-agent nivolumab, a programmed cell death-1 (PD-1) inhibitor, showed that a model involving 9 tumor exome-based parameters was significantly predictive of progression-free survival (PFS) (P <.0001) and overall survival (OS) (P =.002). (here)

Alexander E. Drilon, MD, Memorial Sloan Kettering (MSK), discusses rare drivers in non–small cell lung cancer (NSCLC). (here)

Merck and GlaxoSmithKline are working together to develop and commercialize the immunotherapy candidate M7824 (bintrafusp alfa) as a potential treatment for multiple, difficult-to-treat types of cancer.  M7824 is being developed by Merck and will be assisted in these efforts by GSK. The  therapy candidate has a dual mechanism of action, combining a so-called TGF-beta trap with an anti-PD-L1 mechanism. (here)

February 16, 2019

Management of patients with brain metastases from non-small cell lung cancer and adverse prognostic features: multi-national radiation treatment recommendations are heterogeneous  (here)

Autophagy inhibition with chloroquine reverts paclitaxel [Taxol] resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway (here)

February 18, 2019

Non-Small Cell Lung Carcinoma with EGFR Mutations: The Past, Present and Future of EGFR-Targeted Therapies and Beyond.  Conference: March 1, 2019, Philadelphia, Pennsylvania. (here)

The purposes of this study were to investigate whether the use of immune checkpoint inhibitors (ICIs) in advanced non-small-cell lung cancer (NSCLC) would increase the possibility of archiving complete response (CR) and assess the surrogate end points for overall survival (OS).  The CR is a rate event in advanced NSCLC, but the use of ICIs significantly increases the possibility of archiving CR in comparison with CT. PFS is significantly correlated with OS and could be used as a surrogate end point, but not for CRs and ORRs. (here)

Jacob Scott, MD, DPhil, a physician-scientist at Cleveland Clinic, is interested in learning how cancer cells develop and maintain drug resistance from an eco-evolutionary perspective. He studies the evolutionary strategies that cells employ to survive even in the harshest of conditions. One area of focus of his laboratory is to examine the dynamics of sensitive versus resistant cancer cells and how they affect one another's growth under the selective pressure of anti-cancer therapies. (here)

February 19, 2019

Non-small cell lung adenocarcinoma is the most common type of lung cancer but is often difficult to treat. New treatment options have emerged with the class of tyrosine kinase inhibitors, but it has been found that certain genetic mutations in the epidermal growth factor receptor (EGFR) receptor are not as sensitive to this treatment as others. We present a case of a 78-year-old man who was diagnosed with stage IV non-small cell lung adenocarcinoma with an EGFR exon 20 mutations treated with pemetrexed, nivolumab, and then docetaxel. He has lived over four years after his initial diagnosis. This case illustrates the importance of genetic testing of patients to evaluate for specific gene mutations. It highlights the fact that these patients with exon 20 mutations are not sensitive to tyrosine kinase inhibitor treatment and often respond better to chemotherapeutic agents. (here)

February 20, 2019

Elaine Shum, MD, NYU Langone, discusses mechanisms of resistance in patients with oncogene-driven non–small cell lung cancer (NSCLC). // Based on data from the phase III FLAURA and ALEX studies, osimertinib (Tagrisso) and alectinib (Alecensa) have become the recommended frontline treatments for patients with EGFR-mutant and ALK-positive NSCLC, respectively. Physicians are still learning why tumors develop mechanisms of resistance, says Shum. Although there is no substantial insight into why this occurs, there is reason to believe that these targeted agents isolate a clone and allow for another clone to drive the disease undetected. Future studies involving more biopsies at the time of progression will hopefully shed more light on this issue, she adds. (here)

EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib have proven efficacy in terms of progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, an overall view for comparing efficacy and toxicity on a meta-level is lacking. This study compared efficacy and toxicity of first-line treatment with five different EGFR-TKIs by conducting a network meta-analysis (NMA).  // Our study showed a favorable efficacy of osimertinib in terms of PFS and OS compared to all other EGFR-TKIs in patients with NSCLC harboring activating EGFR mutations. Furthermore, gefitinib, erlotinib, and osimertinib were associated with fewer toxicities compared to the other TKIs. Therefore, osimertinib is indicated as a preferable first-line TKI in patients with activating EGFR-mutated NSCLC.  (here)

February 21, 2019

Drug combinations used for the treatment of non-small-cell lung cancer (NSCLC) and melanoma aren’t as effective as they could be. Oncologists haven’t had the right tools to predict drug interactions, other than in costly clinical trials.  That could change with a new algorithm developed by a cross-disciplinary Vanderbilt University team for calculating drug synergy.  The new approach distinguishes drug interactions which translate to quicker, more effective killing of tumors from interactions that may result in fewer side effects. (here)

Sarah B. Goldberg, MD, Yale, discusses strategies for managing central nervous system (CNS) metastases in patients with oncogene-driven non–small cell lung cancer (NSCLC). (here)

Anti-PD-1/L1 therapies, which remove "checkpoints" that prevent the immune system from fighting cancer, have been hailed as a major treatment advance. But not all patients respond to checkpoint inhibitors. Researchers are exploring new ways to improve their efficacy, and a team led by Cedars-Sinai Medical Center has pinpointed a popular blood cancer drug by Bristol-Myers Squibb as a potential booster.  The helper is Sprycel (here)

Nivolumab plus low-dose ipilimumab was effective and tolerable as a first-line treatment of advanced/metastatic NSCLC. TMB of 10 or more mut/Mb was associated with improved response and prolonged progression-free survival in both tumor PD-L1 expression 1% or greater and less than 1% subgroups and was thus identified as a potentially relevant cutoff in the assessment of TMB as a biomarker for first-line nivolumab plus ipilimumab. (here)

Detection of EGFR mutations using target capture sequencing in plasma of patients with non-small-cell lung cancer (here)

Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. (here)

IL-27 inhibits non-small-cell lung cancer cell metastasis by miR-935 in vitro (here)

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The Cuban-developed immunotherapy CIMAvax-EGF in combination with nivolumab appeared safe for patients with advanced non-small cell lung cancer, according to results from the first portion of a phase 1/phase 2 trial. The combination also demonstrated more effectiveness than either agent alone. (here)

“[Although] this is a small study and we will need to verify that these conclusions hold true when we move on to our phase 2 study, these early hints of clinical activity encourage us to continue exploring this combination approach,” lead investigator Grace Dy, MD, division chief for thoracic oncology at Roswell Park Comprehensive Cancer Center, said in a press release.

February 22, 2019

No Benefit Observed With Osimertinib Plus Durvalumab in EGFR-Mutated NSCLC (here)

Mark A. Socinski, MD, executive medical director, AdventHealth Medical Group, discusses the current state of treatment for patients with non–small cell lung cancer (NSCLC). (here)

Crizotinib with or without an EGFR-TKI in treating EGFR-mutant NSCLC patients with acquired MET amplification after failure of EGFR-TKI therapy: a multicenter retrospective study (here)

Metformin promotes survivin degradation through AMPK/PKA/GSK?3β?axis in non–small cell lung cancer (here)

February 23, 2019

Janakiraman Subramanian, MD, a medical oncologist and director of thoracic oncology and director of the Center for Precision Medicine at Saint Luke’s Cancer Institute, discusses tumor biology in lung cancer. (here)

February 25, 2019

First-line nivolumab plus ipilimumab in advanced non–small-cell lung cancer (CheckMate 568): Outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers (here)