ASCO Breakthrough to Highlight Advances in Esophageal, Nasopharyngeal, Lung Cancers

New Treatment Approaches Help Improve Survival, Quality of Life

ALEXANDRIA, Va. - Three important studies detailing new research advances in esophageal, nasopharyngeal, and lung cancers will be presented at the upcoming 2024 American Society of Clinical Oncology (ASCO) Breakthrough Meeting, taking place in taking place in Yokohama, Japan, and online, August 8-10.

New Study Finds Active Surveillance May Help Patients with Squamous Cell Esophageal Cancer Avoid Surgery
Patients with esophageal squamous cell carcinoma (ESCC) who have a complete response to neoadjuvant chemoradiation may be able to delay or avoid surgery by using clinical response evaluations at regular intervals to monitor the body for remaining cancer cells or distant recurrence.

ESCC is a cancer that forms in the cells that line the inner layer of the esophagus. While ESCC only makes up 30% of esophageal cancers in the United States, it is the most common type of esophageal cancer in Asia. ESCC diagnoses in Asia also make up about half of all esophageal cancer diagnoses worldwide.

The standard treatment for locally advanced, resectable ESCC is neoadjuvant chemoradiation followed by an esophagectomy. However, surgery for esophageal cancer is associated with risk of serious complications and reduced quality of life. An unmet clinical need is to determine whether patients with a true complete response can be accurately identified, especially given a high pathological complete response rate observed in esophageal adenocarcinoma after neoadjuvant chemoradiation. The preSINO study was designed to explore whether using diagnostic tests to detect residual disease could accurately identify patients with a clinical complete response after neoadjuvant chemoradiation.

"Our study is important because it addresses whether we can accurately and safely evaluate residual tumors in ESCC after neoadjuvant treatment. Our preSINO study adapted methods from the previous European preSANO trial in esophageal adenocarcinoma to ESCC in Asia and explored ctDNA testing to enhance accuracy. This research helps expand the use of an active surveillance strategy for ESCC to optimize treatment approaches," said lead study author Zhigang Li, MD, PhD, Chief, Department of Thoracic Surgery at Shanghai Chest Hospital.

Patients enrolled in the study were diagnosed with ESCC and underwent a treatment protocol starting with neoadjuvant chemoradiation, followed by clinical response evaluations, and esophagectomy. After the completion of neoadjuvant chemoradiation, patients underwent the first clinical response evaluation using bite-on-bite biopsy at 4 to 6 weeks. If any cancer cells were found during this biopsy, they had immediate surgery. If the cancer had metastasized, patients did not have surgery.

If no cancer cells or metastasis were found, patients received another round of clinical response evaluations at 10 to 12 weeks after neoadjuvant chemoradiation. These tests included a PET-CT scan, another bite-on-bite biopsy, and an endoscopic ultrasound with fine-needle aspiration of lymph nodes. These patients all underwent surgery unless distant cancer spread was found during the PET-CT scan. A blood test was also done for circulating tumor DNA (ctDNA) during clinical response evaluations.

There were 250 patients in this study who had neoadjuvant chemoradiation, followed by diagnostic tests and surgery. The primary endpoint of the study was the false-negative rate of diagnostic tests for detecting major residual disease (TRG3-4 or TRG1-2 with ypN+) in the resected specimen. Eventually, there were 18 out of 133 patients who had major residual disease that were not found by the bite-on-bite biopsies and endoscopic ultrasound with fine-needle aspiration. The false-negative rate was 13.5%, and this met the study's predetermined primary endpoint.

The researchers further assessed how accurately the tests predicted any remaining cancer (a non-pathological complete response). The bite-on-bite biopsies and endoscopic ultrasound with fine-needle aspiration identified residual cancer with 82% accuracy and correctly confirmed that there was no residual cancer 93% of the time.

The study also investigated whether testing for ctDNA during clinical response evaluations was helpful in predicting distant recurrence after neoadjuvant chemoradiation and surgery. For the 75 patients who had tested positive for ctDNA, 21 (28%) developed distant metastases. For the 57 patients with a negative ctDNA test, only 3 (5%) patients developed distant metastases.

Overall, the bite-on-bite biopsies and endoscopic ultrasound with fine-needle aspiration could accurately detect remaining local-regional cancer cells. ctDNA showed promising potential at predicting who was at a higher risk of having systemic residual disease.

"The preSINO trial is a novel prospective study demonstrating the importance of clinical response evaluation after neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. Combining PET/CT and bite-on-bite biopsy with ctDNA based minimal residual disease detection demonstrated improved accuracy in identifying patients with an increased risk of distant metastases and can help support clinicians in determining whether to escalate or de-escalate treatment," said Vishwanath Sathyanarayanan, MD, Medical Oncologist, Apollo Hospitals in Bangalore.

The above information summarizes Abstract 196, "Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study in Asia." View the abstract

Study of Chinese Patients with Low-Risk Nasopharyngeal Cancer Finds Radiation Alone as Effective as Chemoradiation, Sparing Many Patients Severe Side Effects
Updated results from a phase 3 clinical trial conducted in China showed that radiation therapy alone was as effective as treatment with concurrent chemoradiation in patients with low-risk nasopharyngeal cancer, helping patients avoid the potential side effects of chemoradiation, such as hearing loss and severe weight loss.

While rare in other parts of the world, nasopharyngeal cancer is much more common in China, where as many as 25 to 30 men out of every 100,000 men and 15 to 20 women out of every 100,000 women are diagnosed each year. The authors estimate that about 20% to 40% of people with nasopharyngeal cancer have low-risk disease, defined in this study as stage II disease or T3N0 disease, which is cancer that has limited spread to the lymph nodes and low Epstein-Barr virus (EBV) DNA.

The trial included 341 patients in China with low-risk nasopharyngeal cancer who were randomized to receive either radiation therapy alone (172 patients) or the current standard of care, chemoradiation (169 patients).

After a median follow-up of 70.1 months, the 5-year overall survival rate was 95.2% in the radiation therapy alone group vs. 98.2% in the chemoradiation group. The failure-free survival rate, or percentage of people who did not have their cancer come back and did not die from any cause, was 86.2% in the radiation therapy alone group vs. 88.4% in the chemoradiation group. These differences were not statistically significant.

Additionally, more patients experienced hearing impairment in the chemoradiation group than in the radiation therapy alone group (about 31% of patients vs. about 23% of patients, respectively). Serious side effects-including mouth sores, nausea, vomiting, and appetite loss-were less common in the radiation therapy alone group compared to the chemoradiation group (17% vs. 46%, respectively) during treatment.

"In the era of intensity-modulated radiation therapy (IMRT) for low-risk nasopharyngeal cancer, IMRT alone is effective and safe. Patients in the IMRT-alone group had a significantly lower incidence of reported grade 3 or 4 adverse events compared to those who received concurrent chemoradiation. Additionally, patients in the IMRT-alone group reported significantly better quality-of-life scores during treatment," said lead study author Rui Guo, MD, Sun Yat-sen University Cancer Center.

"It is important to see comparable 5-year overall survival among lower-risk patients with nasopharyngeal cancer treated with radiation therapy alone. This data suggests that chemoradiation may yield similar outcomes but add unnecessary toxicity and speaks to the broader theme of tailoring treatment to each patient," said Glenn J. Hanna, MD, Director, Center for Cancer Therapeutic Innovation, Center for Head and Neck Oncology at the Dana-Farber Cancer Institute.

The above information summarizes Abstract 142, "Radiotherapy alone vs radiotherapy with concurrent chemoradiotherapy in patients with low-risk nasopharyngeal carcinoma: Updated results from a multicenter, open-label, non-inferiority, randomized phase III trial." View the abstract

East Asian Patients Benefit When Treated with Selpercatinib for RET Fusion-Positive NSCLC
A new subgroup analysis of data from the phase 3 LIBRETTO-431 trial, examining the outcomes of treatment with selective RET inhibitor selpercatinib among people from East Asia with RET fusion-positive non-small cell lung cancer (NSCLC), found selpercatinib improved progression-free survival, confirming its potential as a safe and effective treatment for this population. These results are consistent with the general population, supporting the use of selpercatinib as preferred first-line treatment in RETfusion-positive NSCLC.

Lung cancer is the second most diagnosed cancer and the leading cause of cancer deaths globally. Around 80% of the people diagnosed with lung cancer will be diagnosed with NSCLC. About 1% to 2% of people diagnosed with NSCLC will have changes to the RET gene called RET fusion.

The phase 3 LIBRETTO-431 study compared how well selpercatinib, a type of targeted therapy called a selective RET inhibitor, worked to treat RET fusion-positive NSCLC compared to a platinum-based chemotherapy with or without pembrolizumab. Researchers conducted a new analysis of the data collected during this trial comparing selpercatinib and the control treatment in patients from several countries in East Asia-including China, Hong Kong, Japan, Republic of Korea, and Taiwan-to confirm if the drug is also effective for this specific patient population. This is important to study because more people are diagnosed with lung cancer in Asia than anywhere else in the world.

Of the 116 East Asian patients included in the analysis, 75 received selpercatinib and 41 received chemotherapy with or without pembrolizumab. After a median follow-up of 19.4 months in the selpercatinib group and 21.2 months in the control group, the median progression-free survival was not yet reached in the selpercatinib group and was 11.1 months in the control group. After 12 months, the percentage of patients whose cancer had not progressed was 72.8% in the selpercatinib group and 41.7% in the control group. The overall response rate was 86.7% in the selpercatinib group and 61% in the control group.

"We cannot always assume that effective therapies in a general population will still be effective and safe in subpopulations. These outstanding results provide confidence that selpercatinib is an effective and safe treatment for East Asian patients with newly diagnosed RET-altered NSCLC," said David R. Spigel, MD, Chief Scientific Officer, Sarah Cannon Research Institute.

The above information summarizes Abstract 214, "Efficacy and safety of 1L selpercatinib in RET fusion-positive NSCLC: LIBRETTO-431 East Asian subgroup analysis." View the abstract

To arrange interviews with the study authors or outside experts, please contact the ASCO Media Team.

ASCO Breakthrough is planned and cohosted by ASCO, the Japan Society of Clinical Oncology, and the Japanese Society of Medical Oncology, along with many other collaborating societies in the Asia Pacific region. The meeting is endorsed by the Japan Ministry of Health, Labor, and Welfare.

Founded in 1964, the American Society of Clinical Oncology, Inc. (ASCO®) is committed to the principle that knowledge conquers cancer. Together with the Association for Clinical Oncology, ASCO represents nearly 50,000 oncology professionals who care for people living with cancer. Through research, education, and promotion of high quality, equitable patient care, ASCO works to conquer cancer and create a world where cancer is prevented or cured, and every survivor is healthy. Conquer Cancer, the ASCO Foundation, supports ASCO by funding groundbreaking research and education across cancer's full continuum. Learn more at www.ASCO.org, and follow us on Facebook, X, LinkedIn, Instagram, and YouTube.