Neoadjuvant Atezolizumab Plus Chemotherapy for Resectable NSCLC
In a phase II study reported in The Lancet Oncology, Shu et al found that neoadjuvant treatment with atezolizumab plus nab-paclitaxel/carboplatin produced a major pathologic response in 57% of patients and a complete pathologic response in 33% of patients with resectable, predominantly stage IIIA...
Atezolizumab Plus Bevacizumab vs Sorafenib in Treatment-Naive Patients With Unresectable Hepatocellular Carcinoma
As reported in The New England Journal of Medicine by Richard S. Finn, MD, and colleagues, the phase III IMbrave150 trial has shown that anti–programmed cell death ligand 1 (PD-L1) plus anti-VEGF therapy with atezolizumab plus bevacizumab improved progression-free and overall survival vs sorafenib ...
FDA Approves Atezolizumab for the First-Line Treatment of Patients With Metastatic NSCLC and High PD-L1 Expression
On May 18, the U.S. Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) for the first-line treatment of adult patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have high programmed cell death ligand 1 (PD-L1) expression (PD-L1 stained ≥ 50% of tumor cells or...
Qi Liu, PhD, on NSCLC: Pneumonitis, Immunotherapy, and Chemotherapy
Qi Liu, PhD, of the U.S. Food and Drug Administration, discusses data that suggest that patients with advanced non–small cell lung cancer who had a past medical history of pneumonitis were more likely to experience treatment-associated pneumonitis in response to immune checkpoint inhibitors or chemotherapy (Abstract CT086).
FDA Pipeline: Two Breakthrough Therapy Designations for Fam-Trastuzumab Deruxtecan-nxki, and More
Over the past few weeks, the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designations for an antibody-drug conjugate in the treatment of gastric and lung cancers. The Agency has also issued Orphan Drug designations for agents being investigated in chronic myeloid...
FDA Approves Nivolumab/Ipilimumab for First-Line Treatment of Patients With Metastatic NSCLC and PD-L1 Tumor Expression ≥ 1%
On May 15, 2020, the U.S. Food and Drug Administration (FDA) approved the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express programmed cell death ligand 1 (PD-L1) at ≥ 1%, as...
Combining Pembrolizumab With IL-12 Electroporation May Improve Clinical Response in Patients With Immunologically 'Cold' Melanoma
Patients with non–immune-infiltrated “cold” tumors have low frequencies of intratumoral tumor-reactive, checkpoint-positive cytotoxic lymphocytes, making them less responsive to checkpoint blockage than patients with immune-infiltrated “hot” tumors. A phase II study by Alain P. Algazi, MD, and...
First-Line Concomitant and Sequential Nivolumab/AVD for Early-Stage Unfavorable Classical Hodgkin Lymphoma
In a phase II German Hodgkin Study Group trial (NIVAHL) reported in JAMA Oncology, Bröckelmann et al found that both concomitant and sequential nivolumab plus AVD (doxorubicin, vinblastine, and dacarbazine) regimens showed efficacy in first-line treatment of early-stage unfavorable classical...
Edward B. Garon, MD, on NSCLC: Long-Term Use of Pemetrexed Plus Platinum With Pembrolizumab
Edward B. Garon, MD, of the University of California, Los Angeles David Geffen School of Medicine, discusses KEYNOTE-189 trial findings that showed adding pembrolizumab to pemetrexed plus platinum—which previously was found to improve overall and progression-free survival—is also safe and has manageable toxicity in long-term use for patients with metastatic nonsquamous non–small cell lung cancer (Abstract CT085).
Spartalizumab for Locally Advanced or Metastatic Anaplastic Thyroid Carcinoma
In a phase II study reported in the Journal of Clinical Oncology, Jaume Capdevila, MD, and colleagues found that the programmed cell death protein 1 (PD-1) inhibitor spartalizumab produced responses in a cohort of patients with locally advanced or metastatic anaplastic thyroid carcinoma, with all...
Byoung Chul Cho, MD, PhD, on NSCLC: Genetic Mutations and Immunotherapy vs Chemotherapy in KEYNOTE-042
Byoung Chul Cho, MD, PhD, of Yonsei Cancer Center and Severance Hospital, discusses the STK11 and KEAP1 mutations in non–small cell lung cancers, and their relationship to the efficacy of pembrolizumab monotherapy vs platinum-based chemotherapy as first-line treatment for PD-L1–positive advanced disease (Abstract CT084).
Durvalumab Plus Chemotherapy for Extensive-Stage Small Cell Lung Cancer
On March 27, 2020, durvalumab (Imfinzi) was approved for use in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer.1,2 Supporting Efficacy Data Approval was based on the findings of the open-label phase III ...
Encorafenib Combined With Cetuximab in Previously Treated BRAF V600E–Mutant Metastatic Colorectal Cancer
On April 8, 2020, encorafenib was approved for use in combination with cetuximab for the treatment of previously treated adult patients with metastatic colorectal cancer with a BRAF V600E mutation detected by a U.S. Food and Drug Administration (FDA)-approved test.1,2 Encorafenib is not indicated...
Highlights From ASH 2019 Included New Data in Leukemia, Lymphoma, Myeloma, and Myelodysplastic Syndromes
The 2019 American Society of Hematology (ASH) Annual Meeting & Exposition featured a cornucopia of sessions. It was impossible to attend all the lectures, symposia, oral presentations, poster presentations, and special events because many were concurrent. Below, we have selected some...
Pooled Analysis Supports Benefit of Dual HER2-Targeted Therapy, but Questions Remain
In the treatment of HER2-positive early breast cancer, patients who receive dual HER2-targeted therapy in both the neoadjuvant and adjuvant settings are less likely to experience recurrence than those who received dual therapy only as neoadjuvant treatment, according to a pooled analysis of...
KEYNOTE-522: A Biomarker Resource for PD-1 Inhibition in Early Triple-Negative Breast Cancer
In the phase III KEYNOTE-522 trial reported in The New England Journal of Medicine and reviewed in this issue of The ASCO Post, Schmid et al1 found that the addition of pembrolizumab to neoadjuvant chemotherapy in stage II or III triple-negative breast cancer significantly improved the pathologic...
Neoadjuvant and Adjuvant Pembrolizumab Improves Outcomes in Early Triple-Negative Breast Cancer
As reported in The New England Journal of Medicine by Peter Schmid, MD, PhD, of Barts Cancer Institute, Queen Mary University of London, and colleagues, analyses in the phase III KEYNOTE-522 trial have shown that the addition of pembrolizumab to neoadjuvant chemotherapy and the use of adjuvant...
Expert Point of View: Basem M. William, MD, MRCP (UK), FACP, and Caron Jacobson, MD
Basem M. William, MD, MRCP (UK), FACP, Director of the T-Cell Lymphoma Program and Member of the Blood and Marrow Transplant Program at The Ohio State University Comprehensive Cancer Center, Columbus, said many of the new-generation bispecific antibodies are “highly promising.” He said they “are...
Bispecific Antibodies Poised to Impact Treatment of Lymphoma and Other Blood Cancers
Studies of second-generation bispecific antibodies were among the highlights of the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition. The bispecific T-cell engager blinatumomab was the first such agent to be approved by the U.S. Food and Drug Administration (FDA) in...
Addition of Pembrolizumab to Docetaxel for Previously Treated Immunotherapy-Naive Patients With Advanced Lung Cancer
In the single-institution phase II PROLUNG trial reported in JAMA Oncology, Oscar Arrieta, MD, and Christian Rolfo, MD, PhD, and colleagues found that the addition of pembrolizumab to docetaxel improved objective response rates and progression-free survival in immunotherapy-naive patients with...
Expert Point of View: Omid Hamid, MD
Omid Hamid, MD, Chief of Research/Immuno-Oncology, The Angeles Clinic & Research Institute, and Co-Director of the Cutaneous Malignancy Program at Cedars-Sinai Cancer Center, Los Angeles, commented on these two studies for The ASCO Post. According to Dr. Hamid, the findings for the tumor...
Novel Treatment Strategies Under Study in Advanced Melanoma
Several novel strategies for the treatment of patients with stage III or IV melanoma showed promise in studies presented at the 2020 ASCO-SITC Clinical Immuno-Oncology Symposium.1,2 Vaccine for High-Risk Patients After Resection A tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine was...
New Guideline on Systemic Therapy for Melanoma Tackles Rapid Developments in Treatment Options
Systemic treatment of melanoma has changed rapidly since the introduction of ipilimumab in 2011. Newer therapies approved for melanoma since that time include immunotherapy, targeted therapy for mutation-bearing tumors, and injectional therapy for cutaneous or palpable lesions. ASCO has released...
Ryan J. Sullivan, MD, on Advanced Solid Tumors: Antitumor Activity With COM701 Plus Nivolumab
Ryan J. Sullivan, MD, of Massachusetts General Hospital Cancer Center, discusses early results on COM701, a first-in-class immune checkpoint inhibitor, which showed preliminary antitumor activity as a monotherapy and in combination with nivolumab in a variety of heavily pretreated patients with advanced or metastatic solid tumors (Abstract CT031).
Grant A. McArthur, MBBS, PhD, on Melanoma: IMspire150 Trial of Atezolizumab, Cobimetinib, and Vemurafenib
Grant A. McArthur, MBBS, PhD, of the Peter MacCallum Cancer Centre, discusses phase III results from a study of previously untreated patients with BRAF V600 mutation–positive advanced melanoma. His team evaluated whether combining vemurafenib and cobimetinib with atezolizumab improved the durability of responses compared with targeted therapies plus placebo (Abstract CT012).
Steven J. O’Day, MD, on Triple-Negative Breast Cancer: Clinical Benefit With Pembrolizumab Plus Imprime PGG
Steven J. O’Day, MD, of the John Wayne Cancer Institute, discusses phase II results for the combination of pembrolizumab with a novel innate immune activator, Imprime PGG, as second-line treatment for patients with metastatic triple-negative breast cancer ( Abstract CT073).
FDA Approves Olaparib Plus Bevacizumab as Maintenance Treatment for Ovarian, Fallopian Tube, or Primary Peritoneal Cancers
On May 8, 2020, the U.S. Food and Drug Administration (FDA) expanded the indication of olaparib (Lynparza) to include its combination with bevacizumab for first-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in...
Chemoimmunotherapy for Pediatric Refractory or Relapsed Neuroblastoma
In an expansion of a Children’s Oncology Group trial reported in the Journal of Clinical Oncology, Mody et al found that the combination of irinotecan, temozolomide, the anti–disialoganglioside GD2 antibody dinutuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) showed...
Nivolumab for Advanced Refractory Biliary Tract Cancer
In a phase II trial reported in JAMA Oncology, Kim et al found that nivolumab showed antitumor activity in patients with advanced refractory biliary tract cancer. As noted by the investigators, there currently is no established second-line systemic treatment for biliary tract cancer. Study Details...
Expert Point of View: Charles Sawyers, MD
“The hypothesis of combining kinase inhibitors with checkpoint inhibitors could be a fantastic idea,” said formal study discussant Charles Sawyers, MD, of Memorial Sloan Kettering Cancer Center, New York. “This trial [IMspire150] is positive, and that is great news. Triple therapy is superior to...
AACR 2020: Triplet Regimen Improves Progression-Free Survival in Advanced Melanoma in IMspire150 Trial
The addition of the checkpoint inhibitor atezolizumab to two targeted therapies (the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib) as initial therapy improved outcomes compared with the two targeted therapies plus placebo in patients with newly diagnosed BRAF V600E/K–mutant advanced ...
AACR 2020: Atezolizumab Alone or in Combination With Cobimetinib for Biliary Tract Cancer
A randomized multicenter study of a combination of immunotherapy with a targeted therapy improved cancer control for some patients with biliary tract cancer, according to research presented by Yarchoan et al at the American Association for Cancer Research (AACR) Virtual Annual Meeting (Abstract...
Abemaciclib/Fulvestrant/Trastuzumab for Patients With Previously Treated HR-Positive, HER2-Positive Advanced Breast Cancer
In the phase II monarcHER trial reported in The Lancet Oncology, Sara M. Tolaney, MD, and colleagues found that the combination of abemaciclib, fulvestrant, and trastuzumab prolonged progression-free survival vs trastuzumab plus standard-of-care chemotherapy in patients with previously treated...
Regorafenib Plus Nivolumab in Advanced Gastric and Colorectal Cancers
In a Japanese phase Ib/dose-expansion trial reported in the Journal of Clinical Oncology, Fukuoka et al found that the combination of regorafenib and nivolumab showed activity in patients with previously treated gastric cancer and colorectal cancer with microsatellite stable/mismatch...
Lajos Pusztai, MD, PhD, on Breast Cancer: I-SPY2 Trial on Durvalumab, Olaparib, and Paclitaxel
Lajos Pusztai, MD, PhD, of Yale Cancer Center, discusses study results on durvalumab in combination with olaparib and paclitaxel as neoadjuvant treatment in patients with high-risk HER2-negative stage II/III breast cancer. Compared with patients who received chemotherapy alone, the combination improved pathologic complete response, even in women with triple-negative breast cancer (Abstract CT011).
Neoadjuvant Nivolumab for Resectable Merkel Cell Carcinoma
As reported in the Journal of Clinical Oncology by Suzanne L. Topalian, MD, and colleagues, neoadjuvant treatment with nivolumab was found to produce pathologic complete response in approximately half of patients with resectable Merkel cell carcinoma enrolled in the phase I/II CheckMate 358 trial....
Negotiating the Obstacles to Conducting Clinical Trials of Immunotherapy During the Coronavirus Pandemic
Coronavirus disease 2019 (COVID-19) is perhaps the biggest challenge health-care systems have ever had to face. As part of a series of interviews The ASCO Post is conducting with oncologists, we talked with Charles G. Drake, MD, PhD, about the impact of COVID-19 on his practice and on the conduct...
FDA Approves Daratumumab and Hyaluronidase-fihj in Multiple Myeloma
On May 1, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) for adult patients with newly diagnosed, relapsed, or refractory multiple myeloma. This new product allows for subcutaneous dosing of daratumumab. Daratumumab and hyaluronidase-fihj...
AACR 2020: I-SPY2 Trial: Durvalumab/Olaparib/Paclitaxel ‘Graduates’ in HER2-Negative Breast Cancer
The I-SPY2 trial found that the combination of the checkpoint inhibitor durvalumab, the PARP inhibitor olaparib, and the taxane paclitaxel followed by doxorubicin/cyclophosphamide as neoadjuvant therapy improved pathologic complete responses vs paclitaxel followed by doxorubicin/cyclophosphamide...
High- vs Low-Dose Anti-CD19 CAR T-Cell Therapy in Patients With Relapsed or Refractory CLL
In a study reported in the Journal of Clinical Oncology by Noelle V. Frey, MD, and colleagues, a higher dose of anti-CD19 chimeric antigen receptor (CAR) T cells was associated with a higher rate of complete response in patients with relapsed or refractory chronic lymphocytic leukemia, with...
Nivolumab/Ipilimumab vs Nivolumab Alone in Recurrent or Persistent Ovarian Cancer
In a phase II NRG Oncology trial (NRG GY003) reported in the Journal of Clinical Oncology, Dmitriy Zamarin, MD, PhD, and colleagues found that the addition of ipilimumab to nivolumab improved objective response rate and progression-free survival in women with persistent or recurrent epithelial...
FDA Approves New Pembrolizumab Dosing Regimen
On April 28, the U.S. Food and Drug Administration (FDA) granted accelerated approval to a new dosing regimen for pembrolizumab (Keytruda)—400 mg every 6 weeks—across all currently approved adult indications, in addition to the current 200 mg every 3 weeks dosing regimen. The approval was based on...
Isatuximab-irfc for Previously Treated Multiple Myeloma
On March 2, 2020, the CD-38-directed cytolytic antibody isatuximab-irfc (Sarclisa) was approved for use in combination with pomalidomide and dexamethasone for adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.1,2...
PD-1 Inhibition in Mismatch Repair–Deficient/Microsatellite Instability–High Cancers Other Than Colorectal Cancer
Mismatch repair (MMR)-deficiency and consequently high DNA microsatellite instability (MSI-H) are associated with high tumor mutational burden. A high mutational load increases the potential number of neoantigens that can be presented by the tumor cell and recognized by host lymphocytes. Detection...
NCI-MATCH Subprotocol Finds Nivolumab Active in Mismatch Repair–Deficient Cancers Other Than Colorectal Cancer
In a study (NCI-MATCH trial subprotocol, arm Z1D) reported in the Journal of Clinical Oncology, Nilofer S. Azad, MD, of Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer, and colleagues found that nivolumab was active in mismatch repair (MMR)-deficient noncolorectal cancers.1 As stated by...
Addition of Isatuximab to Pomalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma
As reported in The Lancet by Michel Attal, MD, of the Institut Universitaire du Cancer Toulouse Oncopole, France, and colleagues, the phase III ICARIA-MM trial has shown that the addition of the CD38-targeted antibody isatuximab to pomalidomide and low-dose dexamethasone significantly improved...
Expert Point of View: John M. Carethers, MD, and Joseph J. Y. Sung, MD, PhD
Session moderators for the CheckMate 142 presentation at the Gastrointestinal Cancers Symposium were John M. Carethers, MD, the John G Searle Professor (and Chair) of Internal Medicine at the University of Michigan, Ann Arbor, and Joseph J. Y. Sung, MD, PhD, the Mok Hing You Professor of Medicine...
CheckMate 142 Updated Analysis: First-Line Nivolumab Plus Low-Dose Ipilimumab in MSI-H/dMMR Metastatic Colorectal Cancer
As a first-line regimen for patients with metastatic colorectal tumors that are microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR), the combination of nivolumab and low-dose ipilimumab yielded an objective response rate of 64%, a complete response rate of 9%, and a disease...
Do HIV Positivity and Autoimmune Disease Preclude Treatment With Checkpoint Inhibitors?
Can patients with cancer and preexisting autoimmune disorders safely benefit from immunotherapy? The answer has been unclear, with only retrospective studies and anecdotal reports guiding oncologists. This subpopulation of patients has largely been excluded from clinical trials out of concerns over ...
What’s the Current Status of Neoadjuvant Immunotherapy?
For several tumor types, can the successes achieved with immunotherapy in the metastatic and adjuvant settings be replicated in the neoadjuvant setting? An explosion in clinical trials—with more than 300 listed on ClinicalTrials.gov—point to “yes.” “The neoadjuvant use of immunotherapy is of great ...
