Camrelizumab With Chemo Before Surgery Shows Superior Responses Over Chemo in Locally Advanced ESCC

Giving the PD-1 inhibitor camrelizumab with chemotherapy before surgery for locally advanced esophageal squamous cell carcinoma (ESCC) offered better responses than chemotherapy alone, according to phase 3 results being presented today¹ at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI), being held in San Francisco, California.

When surgery is possible in ESCC, offering chemotherapy or chemoradiotherapy beforehand is the standard of care, but recurrence occurs in a subset of patients. This phase 3, open-label, randomized trial followed promising phase 2 results published in March 2022 (ChiCTR1900026240).²

Camrelizumab, from Elevar Therapeutics, is approved for 8 indications in China, where about half of the worldwide cases of ESCC occur. The FDA has accepted a new drug application (NDA) for the tyrosine kinase inhibitor rivoceranib in combination with camrelizumab as a frontline treatment for patients with unresectable hepatocellular carcinoma (HCC), Elevar Therapeutics, Inc., announced in a July 2023 press release. FDA’s target action date for this combination in unresectable HCC is May 16, 2024. A pair of posters offering updated data from the phase 3 CARES study (NCT03764293) will be presented at ASCO GI tomorrow. Trials are ongoing studying carmelizumab in liver, lung, breast, and gastric cancers.

According to the abstract, patients with locally advanced ESCC were stratified by clinical stage—stages I and II, stage III, or stage IVa, and then randomized 1:1:1 into 3 groups for 2, 3-week cycles of treatment. Group A received camrelizumab, albumin-bound paclitaxel (nab-paclitaxel) and cisplatin; group B used camrelizumab, paclitaxel and cisplatin; group C received paclitaxel and cisplatin. Patients were scheduled for surgery 4 to 6 weeks following treatment. In addition, carmelizumab was given after surgery every 3 weeks for up to 15 cycles for the first 2 groups.

Co-primary end points were independently assessed pathological complete response (pCR) rate, and investigator-assessed event-free survival. The trial took place between April 2021 and August 2023, enrolling 391 patients; 132 were in group A, 130 were in group B, and 129 were in group C. Most patients had stage III cancer (71.4%; n = 279) with smaller numbers diagnosed at stage I/II (27.1%; n = 106) or stage IVa, (1.5%; n = 6). Tumors were in different location (upper thoracic esophagus, 10.5%; middle, 51.4%; and lower 38.1%).

Results. Most patients completed both neoadjuvant cycles of therapy—97% in group A, 96.2% in group B, and 94.6% in group C—and high percentages advanced to surgery—86.4% in group A, 89.2% in group B, and 79.8% in group C.

The pCR rate was significantly higher In the intention-to-treat population, in the 2 groups receiving camrelizumab: rates were 28.0% in group A, 15.4% in group B, and 4.7% in group C. Additional results showed as follows:

• The difference between group A and C was 23.5% (95%CI, 15.1-32.0) for an odds ratio (OR) of 8.11 (95%CI, 3.28-20.06; 2-sided P < .0001).
• The difference between group B and C was 10.9% (95%CI, 3.7-18.1) for OR of 3.81, (95%CI, 1.48-9.80; 2-sided P = .0034).
• Major pathologic response rates were 59.1% for group A, 36.2% for group B, and 20.9% for group C In the surgical set, with R0 resection rates of 99.1%, 95.7% and 92.2% respectively.
• Incidence of postoperative complications was 34.2% for group A, 38.8% for group B, and 32.0% for group C.
• During neoadjuvant treatment, the incidence treatment-related adverse events grade 3 or above was 34.1%, 28.5% and 28.8%, respectively.

In patients with resectable locally advanced ESCC, investigators conluded, “neoadjuvant camrelizumab with chemotherapy showed superior pCR and a tolerable safety profile compared to neoadjuvant chemotherapy alone.”

Reference

1. Li Y, Qin J, Xue L, et al. Chemotherapy plus camrelizumab versus chemotherapy alone as neoadjuvant treatment for resectable esophageal squamous cell carcinoma (ESCORT-NEO): A multi-center, randomized phase III trial. Presented at: 2023 American Society of Gastrointestinal Cancers Symposium, January 18-20, 2024; San Francisco, CA. Abstract LBA244.
2. Liu J, Yang Y, Liu Z, et al. Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma. J Immunother Cancer. 2022;10(3):e004291. doi: 10.1136/jitc-2021-004291.