Neoadjuvant Chemoradiation Plus Immunotherapy Boosts Responses in Esophageal Cancer

SAN FRANCISCO — Neoadjuvant chemoradiotherapy with or without the investigational PD-1 inhibitor sintilimab significantly increased pathological complete response (pCR) rates compared with neoadjuvant chemotherapy plus sintilimab in patients with locally advanced esophageal squamous cell carcinoma (ESCC), preliminary results from a randomized phase III trial in China showed.

Among 146 patients, the pCR rate was 13% for those who received neoadjuvant chemotherapy plus sintilimab compared with 60% for those who received neoadjuvant chemoradiotherapy plus sintilimab (OR 10.0, 95% CI 3.7-30.8, PP=0.0005), reported Xuefeng Leng, MD, PhD, of the Sichuan Cancer Hospital & Institute.

“Adding sintilimab — or this kind of immunotherapy regimen — to neoadjuvant chemoradiotherapy may improve pathological outcomes without increasing surgical risks,” said Leng at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium. “Neoadjuvant chemoradiotherapy with immunotherapy has the potential to become the new standard of care in the near future.”

In a discussion following the presentation, Harry H. Yoon, MD, of the Mayo Clinic in Rochester, Minnesota, focused on the results from the groups who received sintilimab plus neoadjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy alone, “because these two arms in my opinion are the most relevant when comparing pCR.”

“These arms directly address whether the addition of immunotherapy to chemoradiation can improve the pCR,” he said, noting that the added immunotherapy improved the pCR rate by 13 percentage points.

There are at least two other randomized trials examining neoadjuvant immunotherapy in ESCC that have reported results, he pointed out.

The phase III ESCORT-NEO trial evaluated camrelizumab in combination with chemotherapy versus chemotherapy alone in the neoadjuvant setting and found that the former improved the pCR rate by 23 percentage points (with survival data yet to be reported).

In addition, an interim analysis from another phase III study conducted at Henan Cancer Hospital in China, which compared toripalimab (Loqtorzi) plus chemotherapy to chemotherapy alone, found that the addition of toripalimab increased the pCR rate by 14 percentage points — “very comparable to the difference shown in the current study,” Yoon observed. “However, the Henan Hospital study did not meet its prespecified threshold for survival.”

Thus, while the “promising results [from the current study] build on prior data … caution is needed because it remains unclear to what degree that improved pCR rate translates into improved survival,” he said.

In explaining the rationale behind the study, Leng pointed out that neoadjuvant chemoradiotherapy or chemotherapy is the standard treatment for resectable locally advanced ESCC in East Asia. In the U.S. and other Western countries, the standard of care for fit patients includes neoadjuvant chemoradiotherapy or perioperative chemotherapy with surgical resection.

However, in the immunotherapy era, “the optimal neoadjuvant treatment strategy remains uncertain,” he added.

The SCIENCE trial was conducted at 14 centers in China and included 146 patients who were randomized into three groups — 46 who received sintilimab plus neoadjuvant chemotherapy (nab-paclitaxel and carboplatin; group A), 45 who received sintilimab plus neoadjuvant chemoradiotherapy (group B), and 55 who received neoadjuvant chemoradiotherapy alone (group C).

Eligible patients had thoracic ESCC, had received no prior treatment, and were clinically staged as locally advanced (cT1N2-3M0 or cT2-4aN0-3M0). Median age was 58.8 years in group A, 64.1 years in group B, and 66 years in group C, and 87-93% were men.

Treatment-emergent adverse events were more common in the chemoradiotherapy groups, including lymphopenia (11.1% and 30.9% in groups B and C vs 0% in group A), leukopenia (24.4% and 29.1% vs 4.3%), and neutropenia (8.9% and 16.4% vs 2.2%).

Surgical resection was planned 6 to 8 weeks after the completion of neoadjuvant therapy.

Regarding surgical complications, Leng reported that rates of anastomotic leakage were low (0% in group A, 2.2% in group B, and 5.5% in group C), while pulmonary infection rates were higher (67.4%, 44.4%, and 47.3%, respectively), but with symptoms that were not very severe. No perioperative deaths were reported.

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