NCCRT Wins in ESCC Trial

SAN DIEGO — Neoadjuvant concurrent chemoradiotherapy significantly improves survival outcomes over adjuvant sequential chemoradiotherapy (ASCRT) in patients with locally advanced esophageal squamous cell carcinoma, confirmed the first randomized trial to directly compare the two approaches.

Yaoyao Zhu, MD, Department of Radiation Oncology, Shanghai Pulmonary Hospital, Shanghai, China, presented the new research at the IASLC World Conference on Lung Cancer (WCLC) 2024 on September 10.

Based on the findings, neoadjuvant concurrent chemoradiotherapy (NCCRT) followed by surgical resection “should be regarded as the standard of care for patients with locally advanced esophageal squamous cell carcinoma (ESCC) in the Chinese population,” Zhu said.

Different Approaches in ESCC

Zhu began her presentation by underscoring that in Western countries, NCCRT followed by surgery has been the standard treatment for locally advanced, resectable esophageal cancer since the publication of the CROSS trial in 2012, which compared neoadjuvant therapy plus surgery with surgery alone.

This demonstrated that preoperative chemoradiotherapy improved survival by 34% in patients with potentially curable esophageal or esophagogastric junction cancer, while adverse event rates were deemed “acceptable.”

In contrast, in most centers in China, clinicians opt for performing surgery followed by ASCRT.

Zhu pointed out that as previous randomized controlled trials have used surgery alone as the comparator arm, it has not been shown definitively that NCCRT plus surgery is superior to surgery followed by ASCRT.

The researchers, therefore, conducted the NEOTERIC trial, which enrolled patients with clinically resectable, locally advanced ESCC, defined as clinical stage T1-2N1M0 or T3-4N0-1M0.

They were randomized to one of two arms. The NCCRT arm involved 6 weeks of carboplatin plus paclitaxel chemotherapy alongside radiotherapy delivered as 50.4 Gy over 28 fractions. After an interval of 4-6 weeks, the patients underwent surgery, followed by an optional two cycles of carboplatin plus paclitaxel 4-6 weeks later.

In the ASCRT arm, patients underwent surgery straightaway, waited for 4-6 weeks, then had two cycles of carboplatin plus paclitaxel 3 weeks apart, followed by the same radiotherapy regimen as in the first arm. About 2-4 weeks later, patients could then undergo another two cycles of carboplatin plus paclitaxel.

More Than Doubling of Survival Outcomes

One hundred patients were assigned to NCCRT and 104 to ASCRT. There were no significant differences between the groups in terms of their baseline characteristics.

The vast majority of patients were men, just over two thirds were smokers, and the median age was around 60 years. The median tumor length was approximately 5 cm, and around half of tumors were located in the middle third of the esophagus.

Median disease-free survival was markedly longer with NCCRT, at 51.0 months vs 14.0 months in the ASCRT arm (P = .01). Similarly, median overall survival was far longer with neoadjuvant therapy, at 79.0 months, vs 38.0 months when waiting until after surgery to provide chemoradiotherapy (P = .025).

There were no significant differences in postsurgical complications between the two arms, and no significant differences in rates of grade 3-4 hematologic and nonhematologic toxicities. There were also no chemoradiotherapy-related deaths.

The most common toxicities across the two study arms were esophagitis, neutropenia, thrombocytopenia, and leukopenia.

Overall, the rates of recurrence were significantly lower with NCCRT than with ASCRT (58.0% vs 66.3%; P = .020). This included significant reductions in both locoregional (P = .012) and distant recurrence (P = .009).

Jaffer A. Ajani, MD, University of Texas MD Anderson Cancer Center, Houston, underlined that the experimental arm of the trial, with neoadjuvant chemoradiotherapy, “has been the standard of care in the United States for a long time, particularly for squamous carcinoma.”

However, he said in an interview that it is not a standard of care in China and clinicians continue with adjuvant therapy. This is despite a recent study conducted in Hong Kong that concluded that patients should not be given any treatment after surgery “because they do worse” than those given neoadjuvant therapy, he continued.

While Ajani noted that the current analysis is underpowered to provide a definitive conclusion, it remains “an important study for Chinese patients.”

“Hopefully, it will be well advertised in China, and all the providers switch [to NCCRT]. This could push them to abandon what in the West was considered harmful.”

Ajani explained the reason neoadjuvant therapy performs better than adjuvant chemoradiotherapy is it “may be mopping up some of the micro metastatic disease, which is difficult to do after surgery,” especially as many patients cannot tolerate postoperative treatment.

“It may be that the majority of patients don’t even get [adjuvant therapy], and those who get it don’t seem to benefit.”

Vishwanath Sathyanarayanan, MD, PhD, Senior Consultant, Professor and Academic Advisor, Department of Medical Oncology, Apollo Cancer Centers, Bangalore, India, agreed that the study reinforces that “NCCRT continues to remain the standard of care in locally advanced resectable esophageal squamous cell carcinoma.”

Consequently, there are “no implications for clinical practice” for providers in the West from these study results, “particularly as NCCRT significantly improves outcomes vs ASCRT with a similar toxicity profile,” he said in an interview.

No funding was declared. Zhu declared no relevant financial relationships.