By Laura Williamson, Science Writer
Yesterday’s Clinical Trials session focused on advances in radiation therapy that offer promising new treatments for hard-to-treat cancers and some potential changes to standards of care. The session was moderated by Kenneth Rosenzweig, MD, FASTRO, of the Icahn School of Medicine at Mount Sinai in New York City and by Farzan Siddiqui, MD, PhD, of Henry Ford Health/Henry Ford Hospital in Detroit.
Drs. Rosenzweig and Siddiqui began the session by thanking all patients who participate in clinical trials.
The session’s first presentation was given by Kenneth W. Merrell, MD, MS, of Mayo Clinic in Rochester, Minnesota, who was introduced as one of two recipients of the 2024 Leibel Memorial Award. The Award is given to early- to mid-career American Board of Radiology certified or board-eligible principal investigators chosen each year by the Annual Meeting Steering Committee based on their abstract’s peer-reviewed scores.
Dr. Merrell presented “A Prospective, Phase II Study of 177Lu-Dotatate in Patients with Surgery- and Radiation-Refractory Meningioma: Results of the WHO Grade II/III Cohort.” In this milestone trial, people with surgery- and radiation-refractory meningioma were treated with 177Lu-Dotatate radiopharmaceutical therapy. Six months after treatment, 78% of patients were progression-free, greatly surpassing the benchmark progression-free survival rate of 26% established by prior research.
177Lu-Dotatate is one of the first prospectively evaluated systemic agents to yield promising clinical efficacy for this difficult-to-treat disease, Dr. Merrell said. Dr. Merrell gave an overview of how radiopharmaceuticals work, then spoke about this theranostic trial with regard to the CNS population. This trial achieved its primary endpoint and may mark a significant safety milestone, Dr. Merrell explained.
“We found a therapy with meaningful signals for effectiveness and safety for people with refractory meningioma, a condition with no standard treatment options,” he said. The study showed that the radiopharmaceutical “appears to be a safe and rational therapeutic choice for patients with aggressively growing tumors.”
Next, Gabriella Macchia, MD, of the Radiation Oncology Unit, Responsible Research Hospital in Campobasso, Italy, presented “A Phase 3 Study of Pembrolizumab (Pembro) + Concurrent Chemoradiotherapy (CCRT) for High-Risk Locally Advanced Cervical Cancer (LACC): Safety Findings.”
This randomized, double-anonymized phase III trial found pembrolizumab (versus placebo) plus concurrent chemoradiotherapy followed by pembrolizumab (versus placebo) monotherapy significantly improved progression-free survival and had a manageable safety profile in patients with high-risk, locally advanced cervical cancer.
“These data support the use of pembrolizumab plus CCRT as a potential new standard of care for this patient population,” Dr. Macchia said. Dr. Macchia noted that this trial took place during the COVID-19 pandemic and the Russian/Ukranian war, and thus it was difficult to track patients and for patients to complete care. Adverse advents were similar across both arms and dropped off significantly after the first three months of treatment.
“Hypofractionated Whole-Breast Irradiation with Simultaneous Integrated Boost for Breast Cancer: Primary Analysis of the HYPOSIB-Trial (ARO 2013-05)” was presented by lead study author David Krug, MD, of Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Strahlentherapie in Kiel, Germany.
This randomized, controlled, multi-center European trial is one of three large trials to study hypofractionation with simultaneous integrated boost irradiation in patients with breast cancer who have had breast-conserving surgery. It established non-inferiority in disease-free survival for a simultaneous-integrated boost regimen of 40 Gy to the breast and 48 Gy to the tumor bed in 16 fractions, compared to moderate hypofractionation with a sequential boost, conventional fractionation with sequential or simultaneous integrated boost. After five years, both arms demonstrated high local control rates and comparable late toxicity.
“In conjunction with the results of RTOG 1005 and IMPORT HIGH, the results of HYPOSIB demonstrate that moderate hypofractionation with simultaneous integrated boost can be considered standard of care,” Dr. Krug said.
Kimberly Corbin, MD, of the Mayo Clinic Alix School of Medicine served as a discussant for Dr. Krug’s presentation. Dr. Corbin sought to explain how the results of the above trial could be integrated into “best breast” practice. In her analysis of Dr. Krug’s presentation, Dr. Corbin explored the data and emphasized that the youngest patients gained the most from boost. “We must remain thoughtful of who to treat with boost in breast radiation,” Dr. Corbin said. Patient quality of life and favorable outcomes are of the utmost importance, Dr. Corbin said. Integrated boosts, according to this trial, are non-inferior to sequential boosts. Dr. Corbin also predicted an increase in IMRT. Dr. Corbin also predicted an increase in the use of IMRT in performing boost radiation.
Next, “Pirfenidone in the Treatment of Radiation-Induced Lung Injury: A Randomized, Controlled, Multicenter Clinical Trial” was presented by lead study author Ming Chen, MD, of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Sun Yat-sen University in Guangzhou Guangdong, China. The study showed pirfenidone could significantly improve lung function, mild to moderate radiation pulmonary fibrosis and acute pulmonary exacerbation-free survival in patients with RILI compared with the control group, with an acceptable safety profile. The drug was well tolerated by 81% of patients who received it. Dr. Chen explained this was the first randomized clinical trial to examine RILI’s pathological process, and that the optimal duration of treatment could not yet be determined based on current data. Additionally, its role in more advanced pneumonitis is unclear.
Vedang Murthy, MD, of Tata Memorial Hospital, Mumbai, India, next presented “Bladder Adjuvant RadioTherapy (BART): Acute and Late Toxicity from A Phase III Multicenter Randomized Controlled Trial.” According to the authors, this is the largest RCT of adjuvant RT in bladder cancer.
This multicenter, phase III randomized trial confirmed that the combination of surgery, chemotherapy, and adjuvant radiotherapy can offer better outcomes for those with high-risk bladder cancer, safely eradicating any microscopic disease that may remain after surgery.
“The BART trial was born out of the pressing need to address a crucial gap in treatment of advanced bladder cancers,” Dr. Murthy said. “While chemotherapy helps manage systemic disease, locoregional recurrences are significant yet underappreciated. Older trials showed that adjuvant radiotherapy could improve locoregional control but fell out of favor due to high toxicity with outdated radiation methods. Today, however, advances in radiation technology and precision targeting have changed the game.” A scientific paper about this presentation was published in the Red Journal concurrently with this session.
“As follow-up continues, the results of the BART trial may reshape how we treat bladder cancer, giving future patients a chance at longer, cancer-free lives,” said Dr. Murthy.
Jay Detsky, MD, of the University of Toronto in Ontario, Canada, was introduced as the second Leibel award winner. He presented “MR-Linac On-Line Weekly Adaptive Radiotherapy for High Grade Glioma (HGG): Results from the UNITED Single Arm Phase II Trial.”This single arm, phase II trial tested the safety of feasibility of weekly on-line MR-Linac (MRL) adaptive radiotherapy with concurrent temozolomide (chemoRT), with a reduced 5 mm clinical target volume (CTV) margin, for patients with newly diagnosed high-grade glioma (grade 4 astrocytoma or IDH-wildtype glioblastoma).
“This trial confirms that CTV reduction, with adaptation, can safely spare brain tissue from radiotherapy,” Dr. Detsky said. “Further trials are required to determine if this benefit translates to reductions in adverse events and improves quality of life.”
“Short-term Androgen Deprivation Therapy and High-dose Radiotherapy in Intermediate- and High-risk Localized Prostate Cancer: Results from the GETUG 14 Randomized Phase III Trial,” was presented by lead study author Nicolas Demogeot, MD, of CLRCC Institut de Cancérologie de Lorraine, Vandoeuvre-Lès-Nancy, France.
The trial found short-term androgen deprivation therapy improves disease-free survival in intermediate and high-risk prostate cancer patients receiving high dose (80 Gy) radiotherapy, with no differences in safety or quality of life.
“This trial is significant because it further demonstrates the importance of ADT in intermediate and high-risk prostate cancer,” Dr. Demogeot said. “It will allow for a larger cohort in future meta-analyses.”
The session concluded with a presentation from Dr. Ou-ying Yan, a student of Xin Wang, MD, of West China Hospital, Sichuan University, Chengdu, Sichuan, China, who reported findings from “A Multicenter Phase III Randomized Clinical Trial Comparing the Efficacy of an Adjuvant SOX Chemotherapy Regimen with SOX Combined with a Simultaneous Radiotherapy Regimen after D2 Radical Resection for Gastric Cancer.”
This phase III, randomized trial sought to detect whether adjuvant chemoradiotherapy would have a survival benefit in gastric cancer patients with high risk factors, such as being in stage T4 or having positive lymph nodes after D2 dissection. It compared the efficacy of two postoperative adjuvant treatment strategies, SOX (Oxaliplatin and S-1) chemotherapy plus concurrent chemoradiotherapy (SOXRT) as well as SOX alone. While both treatment strategies were well tolerated, researchers found no survival benefit with addition of radiation therapy in these patients.
