pCR Rate Improves With Camrelizumab Triplet

The neoadjuvant combination of camrelizumab, nab-paclitaxel (Abraxane), and cisplatin demonstrated statistically significant enhancements in pathologic complete responses (pCRs) compared with solitary chemotherapy in individuals diagnosed with resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC), according to results from the phase 3 ESCORT-NEO/ NCCES01 trial (ChiCTR2000040034) that were presented at the 2024 Gastrointestinal Cancers Symposium in San Francisco, California.¹

Results showed that the pCR rate in the intention-to-treat (ITT) population given camrelizumab with nab-paclitaxel and cisplatin (n = 132) was 28% (95% CI, 20.6%-36.5%) compared with 15.4% (95% CI, 9.7%-22.8%) with camrelizumab plus paclitaxel/cisplatin (n = 130), and 4.7% (95% CI, 1.7%-9.8%) with paclitaxel/cisplatin (n = 129). This was a 23.3% difference between the camrelizumab nab-paclitaxel/cisplatin and chemotherapy-alone arms (95% CI, 15.1%-32.0%; P = .0034). The odds ratios were (95% CI, 3.28-20.06) and 3.81 (95% CI, 1.48-9.80), respectively.

“ESCORT-NEO/NCCES01 is the first phase 3 trial evaluating neoadjuvant immunotherapy plus chemotherapy vs chemotherapy for LA-ESCC,” Yin Li, MD, PhD, FRCS, of the Department of Thoracic Surgery at the National Cancer Center/Cancer Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, said in a presentation during the meeting. “Camrelizumab plus chemotherapy significantly improved pCR rates in the ITT population, with a consistent trend of improvement across subgroups. Neoadjuvant camrelizumab plus chemotherapy may hold promise as a potential standard of care [in] the neoadjuvant treatment for LA-ESCC."

Globally, esophageal cancer is the seventh most common malignancy, and Li noted that there is an unmet need for novel therapies following failure of surgery in patients with LA-ESCC. Camrelizumab is a PD-1 inhibitor that has been approved for use in combination with cisplatin and paclitaxel for the first-line treatment of patients with advanced ESCC in China.

The multicenter, open-label, randomized, phase 3 ESCORT-NEO/NCCES01 trial included patients aged 18 to 75 years who had histologically confirmed, resectable thoracic LA-ESCC (stages T1b-3N1-3M0 or T3NOMO). They were required to have an ECOG performance status of 0 or 1 and could not have received prior treatment.

Patients were randomly assigned 1:1:1 to receive camrelizumab plus nab-paclitaxel and cisplatin every 3 weeks for 2 cycles followed by surgery and subse uent camrelizumab every 3 weeks for up to 15 cycles (group A); camrelizumab plus paclitaxel and cisplatin every 3 weeks for 2 cycles followed by surgery and subsequent camrelizumab every 3 weeks for up to 15 cycles (group B); or paclitaxel and cisplatin alone every 3 weeks for 2 cycles followed by surgery and subse uent surveillance group . Nab-paclitaxel was given intravenously (IV) at 125 mg/m² on days 1 and 8 every 3 weeks, paclitaxel was given IV at 175 mg/m² on day 1 every 3 weeks, and cisplatin was given IV at 75 mg/m² on day 1 every 3 weeks. Camrelizumab was administered at 200 mg IV on day 1 every 3 weeks.

Patients were stratified by disease stage (stages I to II vs IVA). The coprimary end points were pCR, assessed by a blinded independent review committee, and investigator-assessed event-free survival (EFS). Secondary end points comprised molecular pathologic response (MPR), R0 resection rate, ypTNM staging, disease-free survival, overall survival, and safety. Exploratory end points included biomarkers and patient-reported outcomes.

In group A, 129 patients completed 2 cycles of treatment; 18 did not undergo definitive surgery due to patient refusal n or surgery intolerability (n = 4). In group B, 125 patients received 2 cycles of therapy patients did not undergo surgery due to patient refusal (n = 4), surgery intolerability (n = 3), preoperative death (n = 1), or other reason (n = 6). Finally, in group C, 122 patients completed 2 cycles of therapy; patients did not undergo definitive surgery due to patient refusal (n = 12), loss to follow-up (n = 1), or other reason (n = 9).

Regarding baseline characteristics across the treatment arms, the median age was 63.7 years (range, 44-75) and 15.1% of patients were women. A total of 19.5% of patients had an ECOG performance status of 1, and more than half had a middle tumor location (51.4%). Most patients had T3 stage (86.4%), N1 stage (55%), and stage disease III disease (71.3%). Three-fourths of data showed that the camrelizumab/nabpaclitaxel/cisplatin regimen improved pCR vs chemotherapy alone across all prespecified subgroups, including age, sex, clinical stage, PD-L1 TPS or CPS, ECOG performance status, and tumor location.

In the ITT population, the MPR rates were 59.1% (95% CI, 50.2%-67.6%), 36.2% (95% CI, 27.9%-45.0%) and 20.9% (95% CI, 14.3-29.0%) in groups A, B, and C, respectively. This translated to a 15.3% difference (95% CI, 4.7%-26.2%) between arms A and and a . difference between arms B and C, with ORs of 5.51 (95% CI, 3.189.56) and 2.19 (95% CI, 1.25-3.84), respectively.

In group A, the tumor regression grade was 1 for 41.2% of patients, 2 for 21.1% of patients, 3 for 26.3% of patients, 4 for 11.4% of patients, and 5 for 0% of patients. In group B, these respective rates were 19.8%, 18.1%, 31%, 29.3%, and 1.7%. In group C, these rates were 6.8%, 11.7%, 31.1%, 45.6%, and 4.9%, respectively.

Li also provided a surgery summary of the treatment arms. The definitive surgery rate was 86.4% in group A, 89.2% in group B, and 79.8% in group C. Most patients underwent the McKeown surgical procedure, as seen in group A (93.9%), group B (91.4%), and group C (92.2%).

The median duration of surgery was 4.3 hours (range, 2.6-8.9) in group A, 4.2 hours (range, 2.8-7.2) in group B, and 4.2 hours (range, 2.9-10.8) in group C. Most patients had a margin status of 0 (99.1%, 95.7%, and 92.2% of patients, respectively). In group A, 1 patient died within 30 days and 2 died within 90 days. Additionally, 2 patients each died within 30 and 90 days in group B and 1 patient each died within 30 and 90 days in group C.

Any-grade and grade 3 or higher surgical complications occurred in 34.2% and 6.1% of patients in group A, respectively; these rates were 38.8% and 12.1% in group B and 32% and 6.8% in group C. In group A, the most common complications included pneumonia (any grade, 10.5%), recurrent laryngeal nerve injury (any grade, 9.6%), and dysrhythmia (any grade, 6.1%). In group B, the most common complications were pneumonia (any grade, 18.1%; grade≥3, 0.9%), recurrent laryngeal nerve injury (any grade, 9.5%; grade≥, 0.9%), and pleural effusion (any grade, 10.3%; grade≥3, 6.0%).

Grade 3 or higher preoperative treatment-emergent adverse effects (TEAEs) occurred in 34.8%, 31.5%, and 29.6% of patients in groups A, B, and C, respectively. TEAEs leading to discontinuation of camrelizumab occurred in 0.8% of those in both groups A and B. Chemotherapy discontinuation due to TEAEs occurred in of those in group A, 3.8% of those in group B, and 0.8% of those in group C.

Grade 3 or higher preoperative treatment-related AEs (TREAs) occurred in 34.1%, 29.2%, and 28.8% of patients in groups A, B, and C, respectively. One patient each in groups A and had TRAEs that led to camrelizumab discontinuation; 4 patients in arm A, 5 in arm B, and 1 in arm experienced TRAEs that led to chemotherapy discontinuation. One patient in arm B had a TRAE that led to death. Serious AEs occurred in 7.6% of patients in group A, 9.2% of those in group B, and 5.6% of those in group C.

Preoperative immune-related AEs occurred in 27.3% (grade≥3, 4.5%) and 24.6% (grade≥3, 3.8%) of patients in groups A and B, respectively. Li concluded that the study continues to mature for EFS.

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. J Clin Oncol. 2024;42(suppl 3):LBA244. doi:10.1200/JCO.2024.42.3_ suppl.LBA244