An ASCO expert panel has developed a comprehensive guideline for immunotherapy and targeted therapy in patients with advanced gastroesophageal cancer.1 The guideline is based on the many recent advances in immunotherapy and targeted therapy. “The role of immunotherapy has changed practice in the...
Two phase III trials evaluating the addition of drugs targeting PD-1 to chemotherapy—RATIONALE 305 and CheckMate 649—confirmed the benefit of this approach as first-line therapy for advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma, in findings presented at the 2023 ASCO GI...
Session co-moderator, Pretesh R. Patel, MD, Associate Professor of Radiation Oncology at Winship Cancer Institute of Emory University, shared his thoughts on the Neo-AEGIS1 findings with The ASCO Post. “I think we continue to have equipoise about chemoradiation and perioperative chemotherapy in...
A randomized trial that sought to determine the optimal approach to treating locally advanced esophageal or gastroesophageal junction cancer has ended in “equipoise,” according to the investigators of the Neo-AEGIS trial. In a study reported at the 2023 ASCO GI Cancers Symposium, perioperative...
Results of the interim analysis of KEYNOTE-859 are in, and they confirm the overall survival benefit of first-line immunotherapy plus chemotherapy in advanced gastric cancer. Pembrolizumab plus a fluoropyrimidine- and platinum-containing doublet provided a statistically significant improvement in...
Kohei Shitara, MD, of Japan’s National Cancer Center Hospital East, discusses the SPOTLIGHT study’s phase III findings on zolbetuximab plus mFOLFOX6 as first-line treatment for patients with the biomarker claudin-18.2–positive and HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. The regimen seems to have led to an improvement in both progression-free and overall survival, with survival benefits also observed across most subgroups. Zolbetuximab plus mFOLFOX6 is potentially a new standard-of-care treatment for this population (Abstract LBA292).
Filippo Pietrantonio, MD, of Italy’s Istituto Nazionale dei Tumori, discusses phase II results from the INFINITY trial of tremelimumab and durvalumab as neoadjuvant treatment of patients with microsatellite instability–high (MSI) resectable gastric or gastroesophageal junction adenocarcinoma (GAC/GEJAC). These results open the way to investigate nonoperative management in patients with clinical, pathologic, and molecular complete response after T300/D (300 mg of tremelimumab and 1,500 mg every 4 weeks of durvalumab) (Abstract 358).
Nick Pavlakis, PhD, MBBS, of Australia’s Royal North Shore Hospital, discusses phase III findings from the INTEGRATE IIa study of regorafenib vs placebo in refractory advanced gastroesophageal cancer. The trial provides a platform for the investigation of combination therapy with an immune checkpoint inhibitor, now underway in the INTEGRATE IIb study, which is evaluating regorafenib plus nivolumab compared with standard chemotherapy in patients with this type of cancer who have received two lines of prior therapy (Abstract LBA294).
Initial data from the global phase III SPOTLIGHT trial could herald the use of a new targeted agent for a subset of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. First-line treatment with zolbetuximab, which targets the transmembrane protein claudin 18.2...
Tolerability and efficacy results—including the first overall survival data—from a phase II trial examining first-line zanidatamab, an investigational HER2-targeted bispecific antibody, in combination with chemotherapy for patients with HER2-expressing metastatic gastroesophageal adenocarcinoma...
As reported in the Journal of Clinical Oncology by Yamaguchi et al, an exploratory cohort analysis in a Japanese/South Korean phase II trial (DESTINY-Gastric01) indicated that fam-trastuzumab deruxtecan-nxki (TDX-d) showed activity in previously treated—but anti-HER2 treatment–naive—patients with...
In the phase II FIGHT trial reported in The Lancet Oncology, Zev A. Wainberg, MD, and colleagues found numerically better progression-free survival with the addition of the anti-FGFR2b antibody bemarituzumab to mFOLFOX (modified fluorouracil, leucovorin, and oxaliplatin) in patients with...
Esophageal adenocarcinoma is a type of cancer affecting the mucus-secreting glands of the lower esophagus and is the most common form of esophageal cancer. It is often preceded by Barrett’s metaplasia, a deleterious change in cells lining the esophagus. Though the cause of esophageal adenocarcinoma ...
In a systematic review and meta-analysis of phase III trials of immune checkpoint inhibitor treatment in patients with advanced gastroesophageal cancer reported in JAMA Oncology, Harry H. Yoon, MD, MS, and colleagues found that PD-L1 expression was the strongest predictor of overall survival...
As reported in the Journal of Clinical Oncology by Thierry André, MD, and colleagues, the French (GERCOR) phase II NEONIPIGA trial has shown a high pathologic complete response rate with nivolumab/ipilimumab neoadjuvant therapy in patients with localized deficient mismatch repair...
In patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of the checkpoint inhibitor tislelizumab to first-line chemotherapy significantly improved overall survival vs chemotherapy alone, according to an interim analysis of the global phase III RATIONALE-306 trial....
A team of researchers believe they have identified a cell-signaling pathway responsible for the development of esophageal adenocarcinomas, an aggressive type of esophageal cancer that has gradually become more common, even in younger people. Research published by Venkitachalam et al in...
As reported in JAMA Oncology by Stein et al, the German phase II INTEGA trial showed improved survival with the addition of modified FOLFOX6 (fluorouracil, leucovorin, oxaliplatin) vs the addition of ipilimumab to trastuzumab/nivolumab in the first-line treatment of patients with advanced or...
In the German phase II PETRARCA trial of the AIO EGA Study Group, reported in the Journal of Clinical Oncology, Hofheinz et al found that the addition of trastuzumab and pertuzumab to perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) improved both the pathologic complete...
On May 27, 2022, nivolumab was approved for use in combination with fluoropyrimidine- and platinum-based chemotherapy and in combination with ipilimumab for the first-line treatment of advanced or metastatic esophageal squamous cell carcinoma.1 Supporting Efficacy Data Approval was based on...
On May 27, 2022, the U.S. Food and Drug Administration (FDA) approved the following for the first-line treatment of patients with advanced or metastatic esophageal squamous cell carcinoma: Nivolumab (Opdivo) in combination with fluoropyrimidine- and platinum-based chemotherapy Nivolumab in...
Adults aged 45 to 64 years experienced a nearly doubled rate of esophageal cancer and a 50% increase in the precancerous condition Barrett’s esophagus between 2012 and 2019, according to a database analysis of roughly 5 million patients presented by Qumseya et al at Digestive Disease Week 2022...
Esophageal cancer is associated with significant morbidity and mortality worldwide, with more than 600,000 new cases and 540,000 deaths in 2020. The squamous cell histology comprises nearly 90% of cases globally, despite its steady decline in the United States over the past 40 years. Historically,...
As reported in The New England Journal of Medicine by Yuichiro Doki, MD, of Osaka University Graduate School of Medicine, Japan, and colleagues, the phase III CheckMate 648 trial has shown improved overall survival with nivolumab combined with chemotherapy or ipilimumab vs chemotherapy alone in...
Delays in surgery for esophageal cancer did not appear to have much impact on patients’ relative survival for early-stage cancer compared with patients who had surgery early, but they did reduce the relative survival rate by almost half for patients with more advanced disease, according to an...
In the phase III RATIONALE-302 trial reported in the Journal of Clinical Oncology, Shen et al found that the anti–PD-1 antibody tislelizumab significantly improved overall survival vs chemotherapy in the second-line treatment of patients with advanced or metastatic esophageal squamous cell...
Using whole-genome sequencing to contrast genomic alterations in patients with stable Barrett’s esophagus compared to patients whose Barrett’s progressed to esophageal adenocarcinoma, Paulson et al reported that DNA changes presaging esophageal cancer can be spotted years before cancer develops....
Gulam A. Manji, MD, PhD, of Columbia University Medical Center, discusses phase II results on perioperative combination chemotherapy and pembrolizumab in patients with resectable gastric cancer. The combination appeared to result in many complete pathologic responses (Abstract CT009).
In a Japanese case-control study reported in JAMA Oncology, Momozawa et al found that germline BRCA1/2 pathogenic variants were associated with an increased risk of biliary tract, esophageal, and gastric cancers, in addition to an increased risk of cancers that have well-established associations...
Zev Wainberg, MD, of the University of California, Los Angeles Medical Center, discusses preliminary data on the safety and efficacy of TTX-030, an anti-CD39 antibody, in combination with budigalimab and FOLFOX for the first-line treatment of locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. The study suggests the regimen may prove to be of benefit as a first-line treatment, regardless of combined positive score status (Abstract CT015).
As reported in the Journal of Clinical Oncology by Maron et al, a retrospective study found that use of EGFR inhibitor therapy was associated with benefit in patients with unresectable or metastatic EGFR-amplified gastroesophageal adenocarcinoma. As stated by the investigators, “Subset analyses...
As reported in The New England Journal of Medicine by Ronan J. Kelly, MB BCh, MBA, of The Charles A. Sammons Cancer Center at Baylor University Medical Center, and colleagues, an interim analysis of the phase III CheckMate 577 trial has shown a significant improvement in disease-free survival with ...
As reported in Nature by Yelena Y. Janjigian, MD, of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center, and colleagues, the first interim analysis of the phase III KEYNOTE-811 trial has shown a significantly higher objective response rate with the addition of...
Over the past year, the U.S. Food and Drug Administration granted approval to several novel drugs and new indications for older therapeutic agents used in gastrointestinal oncology. Cetuximab Plus Encorafenib On September 28, 2021, cetuximab (Erbitux) was approved in combination with encorafenib...
Samuel J. Klempner, MD, Associate Professor at Massachusetts General Hospital and Harvard Medical School, commented on the NEONIPIGA study for The ASCO Post. “This study was the first prospective data set to show what many have suspected—that neoadjuvant immune checkpoint blockade would lead to a...
In patients with resectable microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) gastric and gastroesophageal junction adenocarcinoma, dual checkpoint inhibition with ipilimumab and nivolumab given as neoadjuvant therapy led to a pathologic complete response rate of 58.6%,...
As reported in The Lancet by Jong-Mu Sun, MD, of Samsung Medical Center, Sungkyunkwan University, Seoul, and colleagues, an interim analysis in the phase III KEYNOTE-590 trial has shown that the addition of first-line pembrolizumab to chemotherapy resulted in improved overall and progression-free...
As reported in The Lancet by Yelena Y. Janjigian, MD, of the Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, and colleagues, the phase III CheckMate 649 trial has shown that the addition of first-line nivolumab to chemotherapy resulted in improved overall and...
Stefano Cascinu, MD, of the Comprehensive Cancer Center, Università Vita-Salute, IRCCS-Ospedale San Raffaele, Milan, Italy, was the invited discussant of KEYNOTE-5901 and CheckMate 649.2 “These landmark studies could change the treatment paradigm of advanced esophageal and gastric cancers. They...
Updates of landmark trials of immune checkpoint inhibitors as first-line therapy for advanced HER2-negative esophagogastric cancers were presented at the 2022 ASCO Gastrointestinal Cancers Symposium. The studies upheld previous findings of an overall survival benefit when these agents are paired...
Samuel J. Klempner, MD, Associate Professor at Massachusetts General Hospital and Harvard Medical School, commented on the NEONIPIGA study for The ASCO Post. “This study was the first prospective data set to show what many have suspected—that neoadjuvant immune checkpoint blockade would lead to a...
In patients with resectable microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) gastric and gastroesophageal junction adenocarcinoma, dual checkpoint inhibition with ipilimumab and nivolumab given as neoadjuvant therapy led to a pathologic complete response rate of 58.6%,...
Updates of phase II studies evaluating fam-trastuzumab deruxtecan-nxki (T-DXd) in gastrointestinal cancers were presented at the 2022 ASCO Gastrointestinal Cancers Symposium, continuing to offer support for the antibody-drug conjugate in these malignancies. In HER2-expressing gastric cancer, T-DXd...
In a Danish single-institution study reported in JACC: CardioOncology, Mette Marie A. Søndergaard, MD, of the Department of Cardiology, Aarhus University Hospital, Denmark, and colleagues found a high rate of undetected or inadequately treated preexisting cardiovascular disease (CVD) prior to...
As reported in The New England Journal of Medicine by Doki et al, the phase III CheckMate 648 trial has shown improved overall survival with nivolumab combined with chemotherapy or ipilimumab vs chemotherapy alone in patients with previously untreated advanced esophageal squamous cell carcinoma, in ...
Thierry André, MD, of Sorbonne University and Saint-Antoine Hospital, discusses phase II results from the GERCOR NEONIPIGA study, which suggests neoadjuvant therapy with nivolumab and ipilimumab may be associated with a high pathologic complete response rate in patients with localized microsatellite instability–high or mismatch repair–deficient esophagogastric adenocarcinoma. This study raises the question of whether surgery could be delayed or avoided for some patients (Abstract 244).
Zev A. Wainberg, MD, of the University of California, Los Angeles, discusses an update, of 25 additional months, on phase III safety and efficacy results from the KEYNOTE-062 trial. This study compared pembrolizumab with or without chemotherapy vs chemotherapy alone for patients with PD-L1–positive advanced gastric or gastroesophageal junction adenocarcinoma (Abstract 243).
As reported in The Lancet Oncology by Howard P. Safran, MD, and colleagues, the phase III NRG Oncology/RTOG-101 trial has shown no significant disease-free survival benefit with the addition of perioperative trastuzumab to neoadjuvant chemoradiation in previously untreated patients with...
Multiple comparisons of traditional cytotoxic chemotherapy combinations that began decades ago led to the adoption of the platinum plus fluorouracil doublet as the standard of care for treatment of recurrent or metastatic esophageal cancer.1 Other combinations created by the addition and/or...
Kohei Shitara, MD, of Japan’s National Cancer Center Hospital East, discusses a long-term data follow-up from CheckMate 649, which support the continued use of nivolumab plus chemotherapy as first-line treatment in patients with advanced gastric, gastroesophageal junction, and esophageal adenocarcinomas (Abstract 240).