2019 GU Cancers Symposium: KEYNOTE-426: Pembrolizumab Plus Axitinib vs Sunitinib in Advanced Renal Cell Carcinoma
Results from the randomized, phase III KEYNOTE-426 clinical trial show that first-line therapy with a combination of pembrolizumab and axitinib extended both overall survival (OS) and progression-free survival (PFS) for patients with clear cell metastatic renal cell carcinoma compared with the...
FDA Approves Daratumumab Split-Dosing Regimen
The U.S. Food and Drug Administration (FDA) has approved a split-dosing regimen for daratumumab (Darzalex), a CD38-directed antibody, providing health-care professionals and patients with multiple myeloma an option to split the first infusion over 2 consecutive days. The approval is based on...
Neoadjuvant Combination Checkpoint Blockade in Advanced Melanoma
Neoadjuvant combination checkpoint blockade showed activity among patients with high-risk stage III melanoma in a small study. However, a high incidence of side effects caused the trial to be closed early. These results were published by Rodabe N. Amaria, MD, Assistant Professor of Melanoma...
How Turning ‘Cold’ Tumors Into ‘Hot’ Ones May Improve Response to Immunotherapy
The proliferation of immunotherapeutics in the treatment of cancer over the past decade has revolutionized the way many cancers are treated, especially lung cancer and melanoma, as well as some blood cancers, including leukemia and lymphoma, drastically improving outcomes for many patients with...
Immunotherapy in Patients With HIV Infection and Advanced Cancer
A study published by Cook et al in JAMA Oncology focused on whether treatment with checkpoint inhibitors is both safe and effective in patients with advanced cancer who are also human immunodeficiency virus (HIV)-positive. Because checkpoint inhibitors manipulate the immune system, the concern has...
Machine Learning Identifies Multiple Underlying Factors Predicting Response to Immunotherapy
A research team is using a branch of artificial intelligence known as machine learning to better target immunotherapy to those who will benefit. In a recent study published by Leiserson et al in PLOS One, the team used data from a clinical trial of patients with bladder cancer to...
Real-World Treatment Impact of Newer Agents on Survival of Patients With Metastatic Melanoma
The approval of several new agents for metastatic melanoma in the past several years has led to changes in how the disease is treated and managed. Treatments such as the programmed cell death protein 1 (PD-1) inhibitors pembrolizumab, ipilimumab, and nivolumab; BRAF inhibitors; and MEK inhibitors...
Avelumab in Recurrent or Refractory Ovarian Cancer
In phase Ib results from the JAVELIN Solid Tumor Trial reported in JAMA Oncology, Disis et al found that avelumab produced durable responses in some patients with recurrent or refractory ovarian cancer. In the study, an expansion cohort of 125 women with advanced disease who had received...
Multiple Myeloma Pipeline Filled With CAR T-Cell Therapies
The burgeoning pipeline of chimeric antigen receptor (CAR) T-cell therapies targeting B-cell maturation antigen (BCMA) in multiple myeloma was on full display at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition. A bispecific antibody also made its debut in this busy...
First-Line Trastuzumab Plus Pembrolizumab Shows Efficacy in Patients With Metastatic Esophagogastric Cancer
When added to first-line chemotherapy in patients with untreated metastatic HER2-positive esophageal, gastroesophageal junction, and gastric adenocarcinoma, the combination of pembrolizumab and trastuzumab produced responses in 87% of patients, with 100% of patients experiencing disease control and ...
Lung-MAP Precision Medicine Trial Expands
The Lung Cancer Master Protocol (Lung-MAP), the first precision medicine trial in lung cancer supported by the National Cancer Institute (NCI), is undergoing a major expansion to include patients with all non–small cell lung cancers (NSCLCs). The trial previously tested treatments for people ...
How Effective Is Talimogene Laherparepvec Injection in Metastatic Melanoma?
Injection of a genetically modified virus that induces the body’s own immune cells to attack metastatic melanoma effectively treated almost 40% of patients with tumors that could not be surgically removed, according to findings published by Louie et al in the Journal of the American...
Nivolumab or Nivolumab Plus Ipilimumab in Relapsed Malignant Pleural Mesothelioma
In a French phase II trial reported in The Lancet Oncology, Scherpereel et al found evidence of activity with nivolumab or the combination of nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma. Study Details In the open-label, noncomparative trial, 125 patients...
Avelumab in Previously Treated Advanced Unresectable Mesothelioma
In a phase Ib trial reported in JAMA Oncology, Hassan et al found that the anti–programmed cell death ligand 1 antibody avelumab produced durable responses and a high rate of disease control in some patients with advanced unresectable mesothelioma progressing after platinum and pemetrexed...
Results Reported From the Phase III ANNOUNCE Trial of Olaratumab in Soft-Tissue Sarcoma
The recently reported results of ANNOUNCE, the phase III study of olaratumab in combination with doxorubicin in patients with advanced or metastatic soft-tissue sarcoma, did not confirm the clinical benefit of olaratumab in combination with doxorubicin as compared to doxorubicin, a...
IMpassion130 Trial: Changing the Treatment Landscape in Metastatic Triple-Negative Breast Cancer
THE IMPASSION130 trial—reported in The New England Journal of Medicine by Schmid et al1 and reviewed in this issue of The ASCO Post—was an eagerly awaited study in newly diagnosed metastatic triple-negative breast cancer. To briefly review, 902 patients were randomly assigned in a 1:1 fashion to...
Addition of Atezolizumab to Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: IMpassion130 Trial
AS REPORTED in The New England Journal of Medicine by Peter Schmid, MD, PhD, of the Barts Cancer Institute, Queen Mary University of London, and colleagues, the phase III IMpassion130 trial has shown that the addition of atezolizumab to nanoparticle albumin-bound (nab)-paclitaxel significantly...
Challenge Moving Forward in Breast Cancer Treatment: To Show That New Approaches Change Outcomes
ADVANCES IN treating breast cancer over the past 20 years have brought us to the point where treatment can be confidently de-escalated for some patients, and immunotherapy and precision decision-making may change the way breast cancer is treated for others, William Gradishar MD, FASCO, told the...
PACIFIC Trial of Durvalumab Sets Standard in Stage III Unresectable NSCLC
IMMUNOTHERAPY HAS revolutionized the treatment of lung cancer over the past several years. Although lung cancer is associated with immunosuppression at baseline for most patients, the addition of immune checkpoint inhibitors can overcome that suppression and lead to antitumor immune responses....
Overall Survival in Men and Women Receiving Immune Checkpoint Inhibitors for Advanced Cancers
In a systematic review and meta-analysis reported in JAMA Oncology, Wallis et al found no difference in overall survival benefit in women vs men receiving immune checkpoint inhibitor treatment for advanced solid tumors. The authors noted that a prior analysis had suggested men derived a greater...
Takashi Kojima, MD, on Esophageal Cancer: Results From the KEYNOTE-181 Trial on Immunotherapy vs Chemotherapy
Takashi Kojima, MD, of the National Cancer Center Hospital East, discusses phase III study findings on pembrolizumab vs chemotherapy as second-line treatment for advanced esophageal cancer (Abstract 2).
Jonathan R. Strosberg, MD, on Neuroendocrine Tumors: Results From the KEYNOTE-158 Trial on PD-1 Inhibition
Jonathan R. Strosberg, MD, of the Moffitt Cancer Center, discusses phase II study findings on pembrolizumab as a treatment for advanced neuroendocrine tumors (Abstract 190).
Carl C. Schimanski, MD, PhD, on Colorectal Cancer Liver Metastases: Study Results on Tecemotide After Surgery
Carl C. Schimanski, MD, PhD, of the Municipal Hospital Darmstadt, discusses phase II study findings on adjuvant immunotherapy with tecemotide after colorectal cancer liver metastasectomy (Abstract 480).
Ahmed Omar Kaseb, MD, on Liver Cancer: Results From an Immunotherapy Trial
Ahmed Omar Kaseb, MD, of The University of Texas MD Anderson Cancer Center, discusses phase II study findings on nivolumab alone vs nivolumab plus ipilimumab in patients with resectable hepatocellular carcinoma (Abstract 185).
Patient-Reported Outcomes With Nivolumab Plus Ipilimumab vs Sunitinib in Advanced Renal Cell Carcinoma
As reported in The Lancet Oncology by Cella et al, patient-reported outcomes were better with nivolumab plus ipilimumab vs sunitinib in the phase III CheckMate 214 trial among patients with intermediate- or poor-risk advanced renal cell carcinoma. The ongoing trial showed significantly improved...
2019 GI Cancers Symposium: Pembrolizumab in Pretreated, Advanced Neuroendocrine Tumors
Findings from the phase I KEYNOTE-028 trial, which studied pembrolizumab in a number of solid tumors, showed activity of the immunotherapy in some patients with heavily pretreated neuroendocrine tumors. Now, a phase II basket trial—KEYNOTE-158—is studying the efficacy and safety of...
Adoptive T-Cell Therapy for Progressive Multifocal Leukoencephalopathy
An emerging treatment known as adoptive T-cell therapy has proven effective in a phase II clinical trial for treating progressive multifocal leukoencephalopathy (PML), a rare and often fatal brain infection sometimes observed in patients with cancer and other diseases in which the immune system is...
Novel Therapeutics for Relapsed or Refractory Multiple Myeloma, Part 2
Here is an update on several different studies focusing on novel treatments for patients with relapsed or refractory multiple myeloma presented at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition. The featured therapeutics include the oral agent selinexor in...
2019 GI Cancers Symposium: Durvalumab, Tremelimumab, and Best Supportive Care vs Best Supportive Care Alone in Advanced, Refractory Colorectal Cancer
The phase II CCTG CO.26 trial evaluated whether the combination of durvalumab, a programmed cell death ligand 1 (PD-L1) inhibitor, and tremelimumab, an anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) antibody, plus best supportive care improved survival vs best supportive care ...
2019 GI Cancers Symposium: Pembrolizumab in Second-Line Therapy for Advanced Esophageal Cancer
Pembrolizumab significantly improved overall survival in the second-line setting of advanced esophageal cancer in patients whose tumors tested positive for programmed cell death ligand 1 (PD-L1) with a combined positive score (CPS) of 10 or greater. This was compared to investigator’s choice...
2019 GI Cancers Symposium: Nivolumab vs Nivolumab Plus Ipilimumab in Resectable Hepatocellular Carcinoma
Anti–programmed cell death protein 1 and anti–cytotoxic T-lymphocyte–associated protein 4 antibodies have shown activity in hepatocellular carcinoma. Based on these earlier findings, researchers sought to examine the safety, efficacy, and tolerability of perioperative treatment...
Study Finds High Tumor Mutational Load Is a Predictor of Response to Immunotherapy in Some Cancers
Although the emergence of immune checkpoint inhibitors over the last decade has revolutionized the treatment of patients with metastatic cancers, only a minority of patients experience long-lasting benefit from the therapy. A study investigating the association between tumor mutational burden and...
Is There a Benefit to Adding Rituximab to Methotrexate-Based Chemotherapy in Primary CNS Lymphoma?
In a phase III trial (HOVON 105/ALLG NHL 24) reported in The Lancet Oncology, Bromberg et al found no significant benefit of the addition of rituximab to high-dose methotrexate-based chemotherapy in patients with newly diagnosed primary central nervous system (CNS) lymphoma. Study Details In the...
VISTA Checkpoint Implicated in Pancreatic Cancer Immunotherapy Resistance
Researchers have identified a new potential immunotherapy target in pancreatic cancer, which so far has been notoriously resistant to treatment with immune checkpoint blockade drugs effective against a variety of other cancers. A research team from The University of Texas MD Anderson ...
Nivolumab in Relapsed or Refractory DLBCL Ineligible for or After Failure of Autologous Transplantation
In a phase II trial reported in the Journal of Clinical Oncology, Ansell et al found that nivolumab was associated with low response rates among patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for or experienced failure of autologous hematopoietic cell ...
Updated Survival Analysis of KEYNOTE-024: Pembrolizumab vs Platinum-Based Chemotherapy in Previously Untreated, Advanced NSCLC
As reported in the Journal of Clinical Oncology by Reck et al, an updated analysis of the phase III KEYNOTE-024 trial indicates continued overall survival benefit of first-line pembrolizumab vs platinum-based chemotherapy in patients with advanced non–small cell lung cancer (NSCLC) with a...
Molecular Profiles of BRAF-Mutant Melanomas and Response to Therapy
A study investigating the clinicopathologic features of BRAF V600E– and V600K–mutant melanomas and whether genotype affects response to immunotherapy found that the mutations not only have different clinical phenotypes, but also different molecular features and different...
MSI-H/dMMR Tumors in Prostate Cancer and Response to Immune Checkpoint Blockade
In a study reported in JAMA Oncology, Abida et al found that approximately 3% of patients with prostate cancer had microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) tumors and that some of these patients exhibited durable responses to treatment with immune...
Factors Influencing Response to Pembrolizumab in Various Advanced Cancers
In an analysis from the phase Ib KEYNOTE-028 trial reported in the Journal of Clinical Oncology, Ott et al found that response to pembrolizumab across different cancers was more likely in patients with higher tumor mutational burden, T-cell–inflamed gene-expression profile, and programmed...
Pilot Study of Intratumoral G100 in Merkel Cell Carcinoma
Multiple recent reports have addressed the activity of programmed cell death protein 1 (PD-1) inhibitors, such as pembrolizumab and avelumab, in Merkel cell carcinoma. However, approximately half of all patients who receive these agents do not maintain a persistent response. In an...
Immune Checkpoint Blockade and Tumor-Specific Vaccine for Incurable HPV16-Related Cancer
In a single-center phase II study reported in JAMA Oncology, Erminia Massarelli, MD, and colleagues found combining tumor-specific vaccine and nivolumab (Opdivo) showed evidence of activity in incurable human papillomavirus (HPV) 16–related cancer. The therapeutic vaccine, ISA 101, induces...
Stories of the Scientists Behind Immunotherapy
As the field of immunotherapy accelerates, so does the literature reporting on the path ahead. One of the newer books on the topic is A Cure Within: Scientists Unleashing the Immune System to Kill Cancer. It has a top-notch pedigree: the author, Neil Canavan, is a seasoned journalist with more than ...
Pembrolizumab in Sorafenib-Pretreated Hepatocellular Carcinoma
ON NOVEMBER 9, 2018, pembrolizumab (Keytruda) was granted accelerated approval for treatment of patients with hepatocellular carcinoma previously treated with sorafenib (Nexavar).1,2 Supporting Efficacy Data APPROVAL WAS BASED on durable responses in the phase II KEYNOTE-224 trial...
Illustrating Genius
FOUR AND A HALF YEARS AGO, author Neil Canavan attended a scientific conference to learn what he could about the then-emerging field of immunotherapy for cancer. After a presentation by Zelig Eshhar, PhD, principal investigator in the Department of Immunology at the Weizmann Institute of Science...
Durvalumab Improves Overall Survival After Chemoradiotherapy in Unresectable, Stage III NSCLC
AS REPORTED in The New England Journal of Medicine by Scott J. Antonia, MD, PhD, of H. Lee Moffitt Cancer Center and Research Institute, and colleagues, the phase III PACIFIC trial has shown significantly improved overall survival, a coprimary endpoint, with the programmed cell death ligand 1...
Optimal Duration of Checkpoint Inhibition in Melanoma Is No More Than 2 Years
For patients with advanced melanoma, the concept of treating to disease progression does not always apply. With many patients responding to checkpoint inhibition for years, when can treatment be safely discontinued? This important clinical question was addressed at the European Society for Medical...
Pembrolizumab Plus Chemoradiotherapy in HPV-Positive Head and Neck Cancer
The addition of pembrolizumab (Keytruda) to a chemoradiotherapy regimen yielded complete response rates of 85% in patients with human papillomavirus (HPV)-positive advanced squamous cell carcinoma of the head and neck. These findings from a phase Ib study were presented at the 2018 Society for...
Update on Immune Checkpoint Inhibitors
Checkpoint inhibitors have moved the field of immuno-oncology to the forefront of cancer treatment and research. However, these agents come with the risk of serious adverse events. To shed light on the toxicities associated with checkpoint inhibitors and other timely issues in the field of...
Immunotherapy-Related Toxicities May Be More Common Than Originally Reported
Immunotherapy has significantly improved the overall survival of patients with non–small cell lung cancer (NSCLC) and is generally better tolerated than traditional chemotherapies, but the results of a retrospective study suggested that immunotherapy side effects may be more common than initially...
ESMO Immuno-Oncology 2018: Second-Line Nivolumab vs Chemotherapy in SCLC
Treatment with nivolumab (Opdivo) did not improve response rates or survival over standard chemotherapy in patients with metastatic small cell lung cancer (SCLC) who relapsed following first-line treatment, according to findings presented by Reck et al at the European Society for Medical...
