Biosimilars

Brain Cancer

HER2+ Breast Cancer

Breast Cancer

CAR T-cell Therapy

COVID-19

Disparities in Cancer Care

Colorectal Cancer

Gastric Cancer

Hepatocellular Carcinoma

Pancreatic Cancer

Gastrointestinal Cancer

Prostate Cancer

Urothelial Cancer

Genitourinary Cancers

Global Oncology

Ovarian Cancer

Gynecologic Oncology

Head & Neck Cancers

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Multiple Myeloma

Myeloproliferative Neoplasms

Non-Hodgkin Lymphoma

Hematologic Oncology

Immuno-Oncology

Lung Cancer

Melanoma & Skin Cancer

Oncology Business Management

Pediatric Oncology

Precision Medicine in Oncology®

Sarcomas

Supportive Care

The novel oral HIF2α inhibitor NKT2152 elicited encouraging responses in patients with previously treated advanced clear cell renal cell carcinoma.

NKT2152 Data Reinforce the Importance of HIF2α Inhibition in Advanced Clear Cell RCC 

Elevated fucosylation and sialylation of serum proteins were negative prognostic factors in RCC after treatment with nivolumab plus cabozantinib or sunitinib.

CheckMate-9ER Post-Hoc Analysis Seeks to Identify Efficacy Biomarkers for Nivolumab/Cabozantinib in RCC

Elacestrant plus abemaciclib demonstrated clinical activity and manageable safety in pretreated ER+/HER2– metastatic breast cancer.

Elacestrant Plus Abemaciclib Demonstrates Clinical Benefit in Pretreated ER+/HER2– Metastatic Breast Cancer

Experts across the lung cancer treatment space impart their key takeaways from research shared at the 2024 IASLC World Conference on Lung Cancer.

Experts Highlight Top Findings From the 2024 IASLC World Conference on Lung Cancer

News

OncClub

All Oncology News

Pipeline Report

Media

Insights

MedNews Week

Medical World News

OncChats

OncLive News Network®

OncLive TV

Peer Exchange

Podcasts

Rapid Readouts

The Talk

Conferences

Conference Coverage

Conference Listing

Events

Giants of Cancer Care

PER Events

Scientific Interchanges

State of the Science Summit / IPC

Webinars

Partners

Publications

Oncology Live®

Oncology Fellows

Supplements and Featured Publications

All Publications

CME/CE

Resources

Interactive Tools

Learning Modules

Presentations

Biomarker Consortium

Subscribe

 in November 2021 as a senior editor and became the website's managing editor in October 2023. Before arriving at MJH Life Sciences, he spent nearly a decade covering professional and high school sports—including the New Jersey Devils and the NHL from 2016 to 2021—for The Star-Ledger and NJ.com. Email: chryan@onclive.com

Articles

The FDA has approved isatuximab plus bortezomib, lenalidomide, and dexamethasone for newly diagnosed, transplant-ineligible myeloma.

FDA Approves Isatuximab Plus VRd for Newly Diagnosed, Transplant-Ineligible Multiple Myeloma

Ashling Wahner joined MJH Life Sciences in 2022. She produces 

, and helps ensure timely publication of news content and announcements from the FDA approval pipeline. She also attends conferences live and virtually to conduct video interviews and produce written coverage. Email: awahner@mjhlifesciences.com

The European Commission has approved frontline zolbetuximab plus chemotherapy for advanced, CLDN18.2-positive gastric and GEJ cancer.

Zolbetuximab Plus Chemotherapy Wins EU Approval for Advanced CLDN18.2+ Gastric/GEJ Cancer

 
Kristi Rosa joined MJH Life Sciences in 2016 and has since held several positions within the company. She helped launch the rapidly growing infectious disease news resource 

. Prior to working at the company, she served as lead copywriter and marketing coordinator at The Strand Theater. Email: krosa@onclive.com

The EMA's CHMP has recommended the approval of subcutaneous daratumumab plus VRd in patients with newly diagnosed, transplant-eligible multiple myeloma.

Subcutaneous Daratumumab Quadruplet Approaches EU Approval for Newly Diagnosed Myeloma

The FDA has granted fast track designation to narmafotinib for the treatment of advanced pancreatic cancer.

Narmafotinib Earns FDA Fast Track Designation for Advanced Pancreatic Cancer

OncLive serves as the connection to oncology, including groundbreaking cancer news and interviews with top oncologists in multimedia formats.

Advertise

About OncLive

Editorial Board

CancerNetwork.com

CGTlive.com

CureToday.com

OncNursingNews.com

TargetedOnc.com

Contact Us

Privacy

Terms & Conditions

Do Not Sell My Information

OncLive - Clinical Oncology News, Cancer Expert Insights

Facebook

Twitter

LinkedIn

Youtube

Spotlight

In-person and virtual events just for HCPs

Specialty

Authors

Dr. Mary J. C. Hendrix from Northwestern University's Feinberg School of Medicine on Metastatic Tumor Cells in Microenvironments

Dr. Hendrix on Metastatic Cells in Microenvironments

A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma

William Harris, MD, presents the study design and rationale for HCRN GI15-225, an open-label, single-arm multicenter, pilot study exploring whether using immunotherapy drugs in combination with locoregional therapies for patients with non-metastatic HCC is safe and beneficial, using pembrolizumab every 3 weeks starting 1 week before initial Y90 radioembolization.

Clinical

Brigatinib in NF2-Related Schwannomatosis with Progressive Tumors

Scott Plotkin, MD, reviews data from a phase II study on brigatinib, a multi tyrosine kinase inhibitor, across various tumor types in patients with NF2-related schwannomatosis.

Long-term Follow-up of Selinexor Maintenance for Patients With TP53wt Advanced or Recurrent Endometrial Cancer: A Prespecified Subgroup Analysis From the Phase 3 ENGOT-EN5/GOG-3055/SIENDO Study

David Miller, MD, reviews a plenary presentation (originally presented at the ASCO 2024 Annual Meeting by Vikky Makker, MD) on the long-term follow-up of the ENGOT-EN5/GOG-3055/SIENDO trial, focusing on selinexor maintenance for patients with TP53 wild-type advanced or recurrent endometrial cancer.

Dr Rafiq on Novel Strategies for CAR T-Cell Engineering in Solid Tumors

Sarwish Rafiq, PhD, assistant professor, Department of Hematology and Medical Oncology, Emory University School of Medicine; program leader, CAR T Basic/Translational Research, Winship Center for Cancer Immunology, Winship Cancer Institute of Emory University, discusses how novel methods for engineering metabolically fit, memory rich CAR T-cells may address barriers to CAR T-cell efficacy in solid tumors.

At the Frontiers in Cancer Immunotherapy 2024 Symposium, Rafiq presented and shared 2 novel approaches to CAR T-cell engineering. The first multi-cytokine particle approach is a CAR T-cell extrinsic method, which involves engineering microparticles to enhance the manufacturing process of CAR T cells, Rafiq states. Since CAR T cells are extracted from patients, modified ex vivo, and then reinfused, this approach focuses on improving the quality of the cells during the manufacturing stage, she details. The engineered microparticles help in enriching the cells for memory phenotypes, which are associated with more durable responses in patients, Rafiq explains.

The second approach is a T-cell intrinsic method where CAR T cells are engineered to secrete their own antagonistic peptide against a novel immune checkpoint, Rafiq says. This modification alters the metabolism and activation profile of the CAR T cells, resulting in a more potent product, she describes.

Before these approaches can be used to manufacture CAR T cells for patients, additional GMP grade studies are needed, Rafiq continues. These studies will indicate whether the extrinsic approach can be implemented in a manufacturing facility to produce CAR T cells. For the intrinsic approach involving vasoactive intestinal peptide receptor antagonists, current research is focused on syngeneic mouse models, which involve the use of mouse CAR T cells in mice that have an intact immune system and tumors, Rafiq says. This research aims to determine if an endogenous immune response can be engaged and to assess any potential on-target off-tumor toxicities from antagonizing the receptor, she explains.

Additionally, studies addressing toxicity with the secreting CAR T cells are necessary to ensure their safety for patients, Rafiq notes. These steps are crucial for advancing these innovative CAR T-cell approaches from experimental stages to clinical application, she concludes.

Sarwish Rafiq, PhD, discusses how engineering metabolically fit, memory rich CAR T-cells may address barriers to CAR T-cell efficacy in solid tumors.

Perioperative chemotherapy with docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT protocol) led to a significant overall survival (OS) benefit vs neoadjuvant chemoradiation (CROSS protocol) in patients with resectable esophageal cancer

 according to findings from the phase 3 ESOPEC trial (NCT02509286) presented during the 

At a median follow-up of 55 months, patients in the intention-to-treat population who received the FLOT protocol (n = 221) achieved a median OS of 66 months (95% CI, 36-not evaluable [NE]) compared with 37 months (95% CI, 28-43) among those who were treated with the CROSS protocol (n = 217; HR, 0.70; 95% CI, 0.53-0.92; 

 = .012). The 3-year OS rates were 57.4% vs 50.7%, respectively, and the 5-year OS rates were 50.6% vs 38.7%, respectively.

Additionally, the median progression-free survival (PFS) was 38 months (95% CI, 21-NE) in the FLOT arm compared with 16 months (95% CI, 12-22) in the CROSS arm (HR, 0.66; 95% CI, 0.51-0.85; 

 = .001). The 3-year PFS rates were 51.6% vs 35.0%, respectively, and the 5-year PFS rates were 44.4% vs 30.9%, respectively.

“Many patients in the US and Europe are still treated with the CROSS radiochemotherapy protocol. Our study shows that patients with resectable esophageal cancer should have FLOT chemotherapy before and after the operation in order to optimize the chance of curing their tumors in the long term,” Jens Hoeppner, FAChirg, FACS, MD, the director of the Department of Surgery at University Medical Center, University of Bielefeld, in Detmold, Germany, stated in a press release.

ESOPEC was a prospective multicenter study that enrolled patients with esophageal adenocarcinoma across 25 sites in Germany between February 2016 and April 2020. Eligible patients needed to be at least 18 years old, have received no prior abdominal or thoracic radiotherapy, have an ECOG performance status of 2 or less, and have adequate organ function. Patients were also required to have pretreatment stage cT1N+, M0 or cT2-4a, N0/+, M0 disease. The presence of squamous or other non-adenocarcinoma histology, gastric cancer, clinical stage cT1cN0 and cT4b disease, or metastatic disease excluded patients from enrollment.

Patients were randomly assigned 1:1 to receive either the FLOT or CROSS protocol. Those in the FLOT arm received repeated doses of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel every 2 weeks over 4 neoadjuvant cycles prior to surgery and 4 adjuvant cycles after surgery. In the CROSS arm, patients received neoadjuvant radiation therapy and concurrent chemotherapy with carboplatin and paclitaxel for 5 cycles in 5 weeks prior to surgery. Following neoadjuvant treatment, patients in both arms waited 4 to 6 weeks before proceeding to surgery. 

The primary end point was OS. Secondary end points included PFS, recurrence-free survival, postoperative pathological stage, postoperative complications, and postsurgical quality of life.

At baseline, the mean age of patients in the FLOT and CROSS arms was 63.1 years (standard deviation [SD], 8.6) vs 62.6 years (SD, 9.8), respectively. Most patients in both arms were male (89.1% vs 89.4%), had clinical T-stage cT3-4 disease (79.1% vs 81.9%), and had clinical N-stage cN+ disease (77.8% vs 81.6%). Overall, 191 patients in the FLOT arm underwent surgery compared with 180 patients in the CROSS arm.

Additional findings from ESOPEC showed that the pathological complete remission rates among patients who underwent surgery in the FLOT arm was 16.8% compared with 10.0% in the CROSS arm. In both arms, complete regression (18.3% vs 13.3%) or near complete regression (25.1% vs 39.4%) was observed. Most patients across both arms underwent an R0 resection (94.2% vs 95.0%).

Patients in the predefined protocol population in the FLOT (n = 207) and CROSS (n = 196) arms achieved a median OS of 66 months (95% CI, 38-NE) vs 39 months (95% CI, 29-45), respectively (HR, 0.72; 95% CI, 0.54-0.96; 

 = .023). The 3-year OS rates were 58.1% vs 52.6%, respectively, and the 5-year OS rates were 51.8% vs 40.5%, respectively.

Results from an exploratory subgroup analysis demonstrated that the OS benefit in favor of FLOT vs CROSS was observed in all subgroups examined. The most pronounced benefit was reported in patients aged less than 60 years (HR, 0.57; 95% CI, 0.34-0.95) and those with clinical T-stage T3-4 disease (HR, 0.68; 95% CI, 0.50-0.92).

Most patients in both the FLOT and CROSS arms started neoadjuvant treatment; these patients comprised the predefined protocol population. A majority of patients in both arms completed neoadjuvant treatment (87.3% vs 67.7%) and received neoadjuvant treatment plus surgery (86.0% vs 82.9%). In the FLOT arm, 63.3% of patients received adjuvant treatment and 52.5% completed adjuvant treatment.

In the 90 days post-surgery, 3.2% of patients in the FLOT arm died compared with 5.6% in the CROSS arm. The 30-day postoperative mortality rates were 1.0% vs 1.7%, respectively At the data cutoff, 97 and 121 patients died in these respective arms.

“Perioperative chemotherapy with FLOT plus surgery improves OS compared with neoadjuvant chemoradiation with CROSS plus surgery in patients with locally advanced, resectable esophageal adenocarcinoma. ESOPEC found that perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with the CROSS protocol for improving survival in resectable esophageal adenocarcinoma,” Hoeppner concluded in an oral presentation. 

Hoeppner J, Brunner T, Lordick F, et al. Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial).

. 2024;42(suppl 17):LBA1. doi:10.1200/JCO.2024.42.17_suppl.LBA1

Chemotherapy before and after surgery may be new standard treatment for some patients with esophageal cancer. News Release. ASCO. June 2, 2024. Accessed June 2, 2024. https://society.asco.org/about-asco/press-center/news-releases/chemotherapy-and-after-surgery-may-be-new-standard-treatment

Perioperative chemotherapy compared to neoadjuvant chemoradiation in patients with adenocarcinoma of the esophagus (ESOPEC). ClinicalTrials.gov. Updated May 8, 2024. Accessed June 1, 2024. https://clinicaltrials.gov/study/NCT02509286

 study was published on June 2, 2024, from the press briefing, and was updated on June 4, 2024, with additional information/data from the oral session.

Perioperative chemotherapy using the FLOT protocol demonstrated a significant overall survival benefit over neoadjuvant chemoradiation (CROSS protocol) in patients with resectable esophageal cancer, as evidenced by the phase 3 ESOPEC trial. With a median follow-up of 55 months, the FLOT protocol achieved a median overall survival of 66 months compared to 37 months with the CROSS protocol. The study suggests that FLOT chemotherapy before and after surgery should be considered to optimize long-term tumor cure rates in these patients.

Perioperative chemotherapy with FLOT improved OS vs neoadjuvant chemoradiation with CROSS in resectable esophageal cancer.

Conference

Perioperative Chemotherapy Prolongs OS vs Neoadjuvant Chemoradiation in Esophageal Cancer

The FDA has approved adjuvant ribociclib (Kisqali) plus an aromatase inhibitor (AI) for the treatment of patients with hormone receptor–positive, HER2-negative stage II and III early breast cancer at high risk of recurrence, including those with node-negative disease.

The approval is based on data from the phase 3 NATALEE trial (NCT03701334), in which the combination demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS) in patients with stage II or III hormone receptor–positive, HER2-negative early breast cancer vs endocrine therapy alone.

"The FDA approval of [ribociclib] for this early breast cancer population, including those with N0 disease, is a pivotal moment in improving our approach to care," Dennis J. Slamon, MD, director of Clinical/Translational Research, UCLA Jonsson Comprehensive Cancer Center and chairman of the Board of Translational Research In Oncology and NATALEE trial lead investigator, said in a news release.

 "Today's approval allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people as a powerful tool that, combined with endocrine therapy, can help further minimize their risk of cancer returning."

Findings from the second interim analysis

, demonstrated that patients who received the combination (n = 2549) achieved a 3-year iDFS rate of 90.4% vs 87.1% in patients who received endocrine therapy alone (n = 2552; HR, 0.748; 95% CI, 0.618-0.906; 

 = .0014). Median follow-up for iDFS was 27.7 months, and the benefit proved consistent across patient subgroups, regardless of disease stage, menopausal status, or nodal status.

 was performed with a median follow-up of 33.3 months and showed sustained iDFS benefit with ribociclib, with 3-year iDFS rates of 90.7% vs 87.6%, respectively (HR, 0.749; 95% CI, 0.628-0.892; 

 from an exploratory analysis that was performed with an additional 10.9 months of follow-up were presented at the 

 The results demonstrated that at a median follow-up of 44.2 months in the intention-to-treat population, the 3-year iDFS rates were 90.8% with ribociclib plus an AI vs 88.1% with an AI alone. At 4 years, the respective iDFS rates were 88.5% vs 83.6% (HR, 0.715; 95% CI, 0.609-0.840; 

NATALEE was a multicenter, randomized, open-label trial comparing ribociclib plus endocrine therapy with endocrine therapy alone in adult patients with hormone receptor–positive, HER2-negative early breast cancer. Eligible patients needed to have anatomic stage IIA, IIB, or III disease following surgical resection, an ECOG performance status of 1 or 0, and have available archival tissue from surgical resection. Those who received prior treatment with a CDK4/6 inhibitor, those with distant breast cancer metastases beyond regional lymph nodes, and those with clinically significant, uncontrolled heart disease were excluded. Prior endocrine therapy up to 12 months prior to randomization was permitted.

Patients who had stage IIA disease included those with N1 disease or those with N0 disease that was grade 2 with evidence of high-risk characteristics, which included Ki-67 expression of 20% or higher, an Oncotype DX Breast Recurrence Score of at least 26, or high-risk characteristics via genomic risk profiling, or grade 3. For stage IIB, the disease must be N0 or N1 and for stage III, the disease must be N0, N1, N2, or N3.

Eligible patients were randomly assigned to receive 400 mg of ribociclib daily in a 3-weeks-on-1-week off manner for 3 years plus an AI, or an AI alone. In both arms, standard-of-care endocrine therapy consisted of letrozole or anastrozole for a duration of at least 5 years plus goserelin in men and premenopausal women.

iDFS using STEEP criteria served as the primary end point of the study. Secondary end points included recurrence-free survival, distant disease-free survival (DDFS), overall survival (OS), patient-reported outcomes, pharmacokinetics, and safety and tolerability. Locoregional recurrence-free survival and gene expression and alterations in circulating tumor DNA/RNA samples were exploratory end points.

Additional findings from the ESMO 2024 presentation demonstrated that ribociclib led to a continued improvement in DDFS (HR, 0.715; 95% CI, 0.604-0.847; 

 <.0001) and a positive trend for OS (HR, 0.827; 95% CI, 0.636-1.047; 

Regarding safety adverse effects (AEs) of special interest in the combination arm included neutropenia (all grade, 62.8%; grade 3/4, 44.4%), liver-related AEs (26.7%; 8.6%), QT interval prolongation (5.4%; 1.0%), and interstitial lung disease/pneumonitis (1.6%; 0.0%).

"With this approval, we are redefining treatment options for a broader population of people impacted by breast cancer and facing the persistent risk of recurrence," Victor Bultó, president, US, Novartis, said.

 "We continue to transform cancer care with [ribociclib], building on its established profile in the metastatic setting and now helping a wide range of people as they strive to stay cancer-free following an early-stage diagnosis."

FDA approves Novartis Kisqali to reduce risk of recurrence in people with HR+/HER2- early breast cancer

 News release. Novartis. September 17, 2024. Accessed September 17, 2024. https://www.novartis.com/news/media-releases/fda-approves-novartis-kisqali-reduce-risk-recurrence-people-hrher2-early-breast-cancer

Slamon DJ, Stroyakovskiy D, Yardley DA, et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer: primary results from the phase III NATALEE trial. 

. 2023;41(suppl 17):LBA500. doi:10.1200/JCO.2023.41.17_suppl.LBA500

Hortobagyi G, Stroyakovsky D, Yardley D, et. al. Ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) as adjuvant treatment in patients with HR+/HER2− early breast cancer: final invasive disease–free survival (iDFS) analysis from the NATALEE trial. Presented at: 2023 San Antonio Breast Cancer Symposium. December 5-9, 2023; Abstract GS03-03.

Fasching PA, Stroyakovskiy D, Yardley DA, et al. Adjuvant ribociclib plus nonsteroidal aromatase inhibitor in patients with HR+/HER2– early breast cancer: 4-year outcomes from the NATALEE trial. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. LBA13. 

A trial to evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer (NATALEE). ClinicalTrials.gov. Updated October 3, 2023. Accessed September 17, 2024. https://clinicaltrials.gov/ct2/show/NCT03701334

The FDA approved adjuvant ribociclib plus an aromatase inhibitor in patients with HR-positive, HER2-negative early breast cancer.

Mary J. C. Hendrix, PhD

Articles

Latest Updated Articles

Latest Conference Coverage