News Digest for the Month of March 2019

Posted on: 2019-04-19 07:30:29

March 1, 2019

Surgery Versus Radiation Therapy in Non-small Cell Lung Cancer.  Treatment options must be carefully considered by a multidisciplinary team weighing the risks and benefits of each.  (here)

A multi-center study led by researchers at The University of Texas MD Anderson Cancer Center revealed that a liquid biopsy test called Guardant360®, is comparable to standard tissue biopsies in detection of guideline recommended biomarkers in advanced non-small cell lung cancer (NSCLC), has a faster turn-around time, and has the potential to support identification of more patients who can be treated with targeted therapy. (here)

In an oral presentation, Dr. Santiago Viteri* (OSE Immunotherapeutics) will provide details on early signs of activity of Tedopi®, a combination of neoepitopes, currently in an ongoing Phase 3 trial in advanced Non-Small Cell Lung Cancer in patients after failure to previous immune checkpoint inhibitors.  (here)

In the latest Johnson & Johnson (J&J) lung cancer-focused effort announced in recent months, AdoRx Therapeutics will partner with Johnson & Johnson Innovation to develop lung cancer treatments, the Scottish drug developer said today.  The new collaboration aims to develop treatments using AdoRx’s fit-for-purpose receptor antagonists. They are designed to modulate the effects of high adenosine levels seen in the tumor microenvironment, which according to AdoRx enable cancer to evade the immune system.  (here)

In a new study, one potential epigenetic therapy in particular that originally showed promise as a cancer treatment ended up exhibiting an opposite effect for lung cancer. Instead of diminishing cancer stem cells, the treatment actually increased the prevalence of tumors in mice. However, during the study, the scientists also discovered a way to reduce these stem cells, thereby reducing lung cancer. Their findings were published in Nature Communications. (here)

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Modulation of peripheral blood immune cells by early use of steroids and its association with clinical outcomes in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors (here)

Assessment of Blood Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Patients With Non–Small Cell Lung Cancer With Use of a Next-Generation Sequencing Cancer Gene Panel (here)

EGFR mutations are significantly associated with visceral pleural invasion development in non-small-cell lung cancer patients (here)

March 2, 2019

Preliminary data suggests the addition of HS-110 to Nivolumab may restore responsiveness to treatment after tumor progression on prior checkpoint inhibitor therapy (here)

Although stereotactic ablative radiotherapy (SABR) is a safe treatment option, results from a recent study suggest that patients with early-stage non–small-cell lung cancer (NSCLC) who undergo SABR alone should be monitored closely for recurrence (here).

Michael D. Mix, MD, assistant professor of radiation oncology at Upstate University Hospital [Syracuse], discusses the use of local consolidative therapy in patients with oligometastatic non–small cell lung cancer (NSCLC).  Aggressive local therapy with radiation is a common approach that Mix has used in practice in an attempt to improve a patient’s overall prognosis. However, the field has had limited evidence to support the clinical benefit of this approach. To date, there has only been 1 prospective study that has demonstrated that physicians may be able to improve not only progression-free survival (PFS), but also overall survival (OS) with the addition of aggressive local therapy. This is typically done with stereotactic body radiation therapy (SBRT) to 3 or fewer sites of metastases, adds Mix.  (here)

A set of features related to density and spatial architecture of TILs was found to be associated with a likelihood of recurrence of early-stage NSCLC. This information could potentially be used for helping in treatment planning and management of early-stage NSCLC. (here)

March 4, 2019

Adding a Vaccine to Immunotherapy in Lung Cancer: Will It Improve Outcomes? (here)

Theralase Technologies a clinical stage pharmaceutical company dedicated to the research and development of light activated Photo Dynamic Compounds (“PDCs”) and their associated drug formulations intended to safely and effectively destroy various cancers, announced today that it has been granted allowance for a United States patent to issue later this year for destroying cancer cells with X-ray activated PDCs. (here)

Lymph-node ratio predicts survival among the different stages of non-small-cell lung cancer: A multicentre analysis (here)

Pumping iron could save your life.  By increasing muscle mass prior to treatment, a greater number of patients are likely to achieve optimal long-term treatment outcomes from PD-1-inhibitor therapy.  (here)

Does Platinum-Based Chemotherapy Still Have a Role in First-Line Treatment of Advanced Non–Small-Cell Lung Cancer? (here)

March 5, 2019

Researchers track clinical course of EGFR-mutant transformed small cell lung cancer.  Patients with EGFR that transformed into SCLC experienced this transformation at an average of 17.8 months following diagnosis, according to results of retrospective study published in Journal of Clinical Oncology.  Further, EGFR-mutant transformed SCLC usually was characterized by RB1, TP53 and PIK3CA mutations; frequent central nervous system metastases; and responses to a platinum-etoposide regimen and taxanes, but not to checkpoint inhibitors. (here)

 Non-Small Cell Lung Cancer: Liquid Biopsy Pinpoints Treatment Options (here)

 Assessment of blood tumor mutational burden as a potential biomarker for immunotherapy in patients with non–small cell lung cancer with use of a next-generation sequencing cancer gene panel (here)

Study Shows Guardant Assay Similar to Tissue Testing for Finding NSCLC Mutations (here)

March 6, 2019

Dr. Heather Wakelee (Stanford) discusses unmet needs for immunotherapy in the treatment of patients with non–small cell lung cancer (NSCLC).  Currently, when one looks at the data with combination chemotherapy and immunotherapy in metastatic disease, there is not a subgroup of patients with NSCLC where this therapy clearly did not show at least some benefit other than those with oncogene-driven disease. Although there are some other effective options available for patients with driver mutations, immunotherapy research in these patients is still a challenge.  To date, checkpoint inhibitors in combination with TKIs have been shown to be very toxic, and even in the absence of toxicity, this approach was not found to be very effective, Wakelee notes. Although chemotherapy combined with immunotherapy may be a potential option in those patients, early data have not been too promising. (here)

March 7, 2019

Pembrolizumab shows durable survival benefit in advanced non-small cell lung cancer // The KEYNOTE-024 trial is designed to evaluate the safety and efficacy of pembrolizumab vs. platinum-based chemotherapy as first-line treatment for patients with NSCLC who have a PD-L1 tumor proportion score of 50% or greater but do not have EGFR/ALK aberrations. (here)

Although EGFR-targeted therapies have led to a survival benefit for patients with non–small cell lung cancer (NSCLC), more evidence-based data are still needed to compare the relative values of new versus first- and second-generation therapies, said Edward B. Garon, MD.  According to Garon, however, the pharmaceutical sector is showing willingness to develop therapies for subpopulations in this disease type, having overcome reservations based on uncertain financial rewards of doing so. In addition, the amount of research into resistance mechanisms is increasing, boding well for useful insight into treatment selection.  (here)

Immunotherapy has emerged as a frontline option for patients with metastatic non–small cell lung cancer, but it is important to note that patients eligible for these trials account for a small portion of all patients with lung cancer, said Mohammad Jahanzeb, MD.  Specifically, there are strict eligibility criteria for immunotherapy trials, especially in lung cancer. Age, autoimmune disease, organ transplantation, and drug addiction are among a list of factors that would make a patient ineligible for enrollment in a clinical trial evaluating the use of an immune-oncology drug.  As such, these patients may miss out on a potential survival advantage, he said. (here)

Blood tumor mutational burden may give insight into which patients with non-small cell lung cancer (NSCLC) may benefit from therapy with anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibodies, according to Chinese researchers. (here)

Management of common adverse events related to first-line dacomitinib use in EGFR mutation-positive non-small-cell lung cancer: a pooled safety analysis (here)

March 12, 2019

Lilly's CYRAMZA® (ramucirumab) Phase 3 RELAY Trial Met Primary Endpoint, Significantly Improving Progression-Free Survival in First-Line Treatment of Patients with Metastatic EGFR-Mutated Non-Small Cell Lung Cancer (here and  here)

PARP Inhibitors May Enhance Immunotherapy Response in Lung Cancer (here)

Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification (here)

Targeting late-stage non-small cell lung cancer with a combination of DNT cellular therapy and PD-1 checkpoint blockade (here)

March 14, 2019

Ramucirumab/Erlotinib Combo Improves PFS in Frontline EGFR+ NSCLC (here)

Immunotherapy has dramatically improved the outlook for select patients with metastatic non–small cell lung cancer (NSCLC), but its reach could extend even further when combined with other approaches, said Naiyer A. Rizvi, MD.  (here)

Aggressive consolidative therapy to the primary lesion and all metastatic sites appeared associated with improved OS among patients with synchronous oligometastatic non-small cell lung cancer, according to study results scheduled for presentation at Multidisciplinary Thoracic Cancers Symposium. (here)

Heather Wakelee, MD, associate professor of medicine, Stanford University Medical Center, discusses the importance of next-generation sequencing (NGS) testing in the treatment of patients with non–small cell lung cancer (NSCLC). (here)

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Our data demonstrate that concurrent EGFR-TKI and WBRT achieves longer iPFS than EGFR-TKI alone in advanced EGFR-mutant NSCLC with brain metastases. In advanced EGFR-mutant NSCLC with three or less brain metastases, EGFR-TKI alone may be an option as a first-line therapy.  (here)

March 15, 2019

Tissue-specificity in cancer: The rule, not the exception  (here)

Biodesix ® today presented new data demonstrating that the VeriStrat ® test is predictive of outcomes for patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) in the first-line setting, even when adjusted for PD-L1 status. (here and here)

Optimal timing and clinical value of radiotherapy in advanced ALK-rearranged non-small cell lung cancer with or without baseline brain metastases: implications from pattern of failure analyses  (hereCan EGFR group learn anything from this study?

March 16, 2019

Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non–Small Cell Lung Cancer.  A Long-term Update of the NRG Oncology/RTOG 0214 Phase 3 Randomized Clinical Trial.  (here)

Early Noninvasive Detection of Response to Targeted Therapy in Non–Small Cell Lung Cancer. // Cell-free tumor load provides a novel approach for evaluating longitudinal changes in ctDNA during systemic treatment with tyrosine kinase inhibitors and serves an unmet clinical need for real-time, noninvasive detection of tumor response to targeted therapies before radiographic assessment.  (here)

March 18, 2019

Profiling preexisting antibodies in patients treated with anti–PD-1 therapy for advanced non–small cell lung cancer (here)

 

March 19, 2018

Journal of Clinical Pathways spoke with Mark A Socinski, MD, AdventHealth, about a recent FDA approval in non-small cell lung cancer (NSCLC) as a result of the Impower150 study, of which he was the lead investigator.  (here)

Mohammad Jahanzeb, MD,Miami Miller School of Medicine, discusses the use of immunotherapy in patients with oncogene-driven non–small cell lung cancer (NSCLC).  //  Tumors that are driven by EGFR, ALK, or more rare alterations are pristine-looking cells with essentially only 1 thing wrong with them—the mutation driving the tumor, says Jahanzeb. As such, it is more difficult for the immune system to detect and attack the disease. Thus far, data has shown that the use of immunotherapy does not seem to benefit these patients. As such, this approach should only be considered after patients have exhausted multiple lines of TKIs and chemotherapy. Immunotherapy is clearly not a first- or second-line option for this patient population, he concludes.  (here)

Rain Therapeutics Announces First Patient Dosed in Phase 2 Trial of Tarloxotinib for the Treatment of Non-Small-Cell Lung Cancer with EGFR Exon 20 Insertion or HER2-Activating Mutations (here)

Pre-treatment 18F-FDG PET-based radiomics predict survival in resected non-small cell lung cancer  (here)

March 22, 2019

Dynavax Technologies announced it will present safety and biomarker data for DV281, its inhaled TLR9 agonist, at the American Association for Cancer Research (AACR) Annual Meeting 2019.  DV281 is Dynavax’s proprietary investigational TLR9 agonist designed specifically for focused delivery to primary lung tumors and lung metastases. (here)

Elaine Shum, MD, medical oncologist, NYU Langone’s Perlmutter Cancer Center, discusses the use of dacomitinib (Vizimpro) in the treatment of patients with EGFR-positive non–small cell lung cancer (NSCLC).  The second-generation EGFR TKI had very impressive data in the ARCHER 1050 study, Shum says, but the toxicity profile of the drug may be reason for concern. With dacomitinib, there is much stronger toxicity than what is typically observed with this class of drugs, especially when compared with osimertinib (Tagrisso), the frontline standard of care. Shum notes that personally, she would not consider using dacomitinib in the frontline due to toxicity alone. However, as more is understood about sequencing EGFR TKIs, dacomitinib could have a potential role in later lines of therapy. (here)

Researchers at The University of Texas MD Anderson Cancer Center revealed the common oncogene KRAS as a possible explanation for why many patients with metastatic colorectal cancer (CRC) do not respond to immune checkpoint blockade (ICB) therapy.  Findings from the study, published in the March 21 online issue of Cancer Cell, shows how KRAS, a key mutation in colorectal cancer, promotes metastasis by controlling the immune-suppressive capabilities of the tumor microenvironment. The study results reveals how KRAS and its downstream target genes interact, supporting further study of a new approach to enhancing ICB therapy.  (here)

Researchers at genetic testing company Illumina and leading cancer hospitals have used a liquid biopsy to detect cancer-driving mutations in patients who lacked analyzable tissue samples.  The noninvasive next-generation sequencing assay identified mutations in around 25% of the patients without analyzable tissue samples, suggesting it can play a role in informing treatment decisions in some circumstances.  However, the inability of the test to detect some mutations in patients with analyzable tissue samples is likely to limit near-term applications of the approach.   (here and here)

Members of the "Tracking Non-Small Cell Lung Cancer Evolution through Therapy" (TRACERx) consortium have started to unravel the complex relationships between immunoediting, immune cell infiltration, neoantigen formation, and clonal evolution in non-small cell lung cancer (NSCLC) tumors. (here)

Aspirin hinders hypoxia-mediated effects that promote the growth of non-small cell lung cancer (NSCLC), according to the results of a recent study in Pathology – Research and Practice. (here)

The interplay between an evolving cancer and a dynamic immune microenvironment remains unclear. // Our results suggest that the immune microenvironment exerts a strong selection pressure in early-stage, untreated non-small-cell lung cancers that produces multiple routes to immune evasion, which are clinically relevant and forecast poor disease-free survival.  (here)

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The efficacy of osimertinib does not significantly vary according to the body size variables of patients with T790M-positive non–small cell lung cancer (NSCLC) who progress on prior EGFR tyrosine kinase inhibitors (TKIs), according to findings from a new study published in Thoracic Cancer.  (here)

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Novocure announced today 48 presentations on Tumor Treating Fields at the American Association for Cancer Research (AACR) Annual Meeting 2019, March 29 through April 3, in Atlanta. For the first time at this conference, a symposium session on Tumor Treating Fields also will be held.  (here)

Results of the KEYNOTE-189 trial dramatically altered initial treatment for patients with advanced-stage non-small cell lung cancer whose tumors do not harbor targetable alterations, according to a presenter at HemOnc Today New York.  However, no data are available to guide subsequent treatment decisions for later-line therapy, Benjamin Levy, MD, associate professor of oncology at Johns Hopkins University said during his presentation.  “For now, chemotherapy with immunotherapy remains the standard in my mind,” Levy said. “Novel immunotherapies or immunotherapy combinations that are rooted in science are desperately needed in this space. It is complicated and vast and will take a lot of sorting out over the next 5 to 10 years.” (here)

Artificial intelligence and radiomics can help specialists predict how patients with non–small cell lung cancer (NSCLC) will respond to chemotherapy, according to new research published in Radiology: Artificial Intelligence.  Approximately 1 in 4 patients have a positive response to platinum-based chemotherapy, a standard first-line treatment of NSCLC. The study’s authors noted that “no clinically validated biomarkers” currently exist that can identify patients who will benefit the most from such treatment. With this in mind, they wanted to see what could be learned about a patient’s possible response by extracting radiomics data from their CT images.  “Our aim in this study was to determine whether an early prediction of response to chemotherapy is possible by using computer-extracted measurements of patterns both within and outside the lung nodule, along with the shape of the nodule, on baseline CT scans,” co-lead author Mohammadhadi Khorrami, MS, of Case Western University in Cleveland, said in a prepared statement.  (here)

Timothy Saettele, MD, interventional pulmonologist at Saint Luke’s Hospital, discusses the benefits of using bronchoscopies in patients with non–small cell lung cancer (NSCLC).  Ten to 15 years ago, advanced bronchoscopic techniques such as endobronchial ultrasound and navigation bronchoscopy were not available. Since then, physicians have gained the ability to see through the walls of the airway with ultrasound technology, to biopsy outside of the airways, and to diagnose lesions in the periphery of the lung.  (here)

March 23, 2019

Although programmed cell death-ligand-1 (PD-L1) expression in tumor tissue has been established as predictive biomarker for the anti-programmed cell death-1 (PD-1) antibody treatment of non-small-cell lung cancer (NSCLC), additional biomarkers are critically needed. We evaluated serum proteins relevant to immune checkpoint blockade in patients with NSCLC treated with nivolumab to identify novel non-invasive predictive biomarkers.  (here)

March 24, 2019

Molecular therapy for the treatment of lung cancer has not evolved enough to adequately extend survival of patients, according to a presenter at HemOnc Today New York.  Understanding primary and secondary resistance in the EGFR, ALK and ROSI genes, turning immune “cold” tumors to “hot” tumors, overcoming secondary immune resistance, improving quality of life and reducing financial toxicity are specific areas where improvement is still needed, Neal E. Ready, MD, PhD, professor of medicine at Duke University, said during a presentation.  (here)

New mechanism to reduce inflammation.  //  In one series of experiments, the team found that cancer cells derived from patients with treatment-resistant non-small cell lung cancer expressed high levels of the SIX1 and SIX2 proteins. The scientists used the CRISPR-Cas9 gene-editing technology to remove the genes that produce those two proteins, making the cancer cells dramatically more sensitive to a promising drug class called SMAC mimetics. (here)

Researchers in Cleveland have found that applying radiomics in the assessment of CT images produces quantitative data points showing characteristics of advanced-stage non-small cell lung cancer inside tumors and in the areas around them that are not visible in the images alone and could distinguish those who would respond well to chemotherapy from those that would not.  (here)

March 25, 2019

Top 10 Immuno-Oncology Collaborations

https://www.genengnews.com/a-lists/top-10-immuno-oncology-collaborations-3/

March 27, 2019

The IMpower150 trial showed significant improvements in progression-free and overall survival with atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP) versus the standard-of-care bevacizumab plus carboplatin plus paclitaxel (BCP) in chemotherapy-naive patients with non-squamous non-small-cell lung cancer. Here, we report the efficacy of ABCP or atezolizumab plus carboplatin plus paclitaxel (ACP) versus BCP in key patient subgroups. // Improved survival was noted for patients treated with ABCP compared with those given BCP in the intention-to-treat population, and in patients with baseline liver metastases.  (here)

Sukhmani Padda, MD (Stanford) discusses the role of immunotherapy in patients with EGFR-positive non–small cell lung cancer (NSCLC).  Immunotherapy has not been the biggest hit yet for this patient population, says Padda. However, it can play a role in a more selective patient population.  Immunotherapy should only be considered for these patients with EGFR-mutant NSCLC after all targeted therapies have been tried, as well as a platinum doublet chemotherapy. However, even in patients with high PD-L1 expression, the response rates with immunotherapy have not been that high. (here)

Role of Targeted Therapy and Immune Checkpoint Blockers in Advanced Non?Small Cell Lung Cancer: A Review (here)

PDIA6 modulates apoptosis and autophagy of non-small cell lung cancer cells via the MAP4K1/JNK signaling pathway (here)

Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma (here)

March 29, 2019

John V. Heymach, MD, PhD: Well, so in 2019, as of right now the TMB is not a marker that’s useful for selecting therapies. It may be in the future. One of the ancillary benefits, in fact I think in some ways what may turn out to be the greatest benefit, is if people are getting TMB, you’re going to find a lot of those driver mutations as an ancillary benefit that people were missing before. That may turn out to be as much if not more of a benefit.  But it also points out that PD-L1 alone will not end up being the full story. There’s other data saying that the genomic markers may also impact it. So right now, I think the message is, everybody should get immunotherapy. We’re refining who’s going to get the most benefit or who would get the most benefit from combination immunotherapy. But still right now unless somebody’s got an overwhelming reason in terms of autoimmune disease or a transplant, as Heather said, there’s nobody that shouldn’t get immunotherapy with non–small cell lung cancer, I think.  (here)

Jason M. Wallen, MD, Upstate University Hospital, discusses technological advances made in non–small cell lung cancer (NSCLC). (here)

Stephen L. Graziano, MD, Upstate Cancer Center, discusses sequencing targeted therapy for patients with non–small cell lung cancer (NSCLC).  In terms of next steps for research, a lot more has to be done to determine the optimal sequencing of therapy, says Graziano. Following frontline therapy, the patient’s specific molecular abnormalities should be taken into account to determine the next line of therapy.  (here)

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Researchers at Osaka University in Japan have identified a key component of physical health associated with response to immunotherapy drugs.  Among people with non-small cell lung cancer, higher levels of muscle mass predicted a better response to PD-1 inhibitor immunotherapy.  (here)

Promising to match more NSCLC patient with targeted drugs, Cambridge spinout Inivata readies US launch of liquid biopsy (here)

Benjamin P. Levy, MD, Johns Hopkins Medicine, discusses the use of entrectinib in patients with oncogene-driven non–small cell lung cancer (NSCLC).  Entrectinib is yet another targeted agent that’s making its way into the NSCLC space. It’s use is currently being evaluated in patients with advanced-stage disease who harbor NTRK fusions or ROS1 rearrangements, Levy says. (here)

March 31, 2019

FGFR Alterations Emerge as Enticing Target in Multiple Tumor Types (here)

Although tumor mutational burden(TMB) is associated with responses to checkpoint inhibitor therapy, more research is needed to better understand how TMB interacts with other genomic correlates of the immune cycle before the biomarker can be incorporated into clinical practice, according to Natalie Vokes, MD, MPhil. (here)

Preliminary Data from Phase 1 Study Evaluating ADXS-NEO Suggest Rapid Immunogenicity and Clinical Activity (here)

Differences in Small Cell vs Non-Small Cell Lung Cancer (here)