Camrelizumab/Chemo Combo Improves Complete Responses in Locally Advanced ESCC

Camrelizumab/Chemo Combo Improves Complete Responses in Locally Advanced ESCC

Combining camrelizumab, nab-paclitaxel (Abraxane), and cisplatin in the neoadjuvant setting demonstrated statistically significant improvements in pathologic complete responses (pCRs) when compared with chemotherapy alone in the treatment of patients with resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC), recent study results showed.

Findings from the phase 3 ESCORT-NEO/NCCES01 trial (ChiCTR2000040034) were presented at the 2024 Gastrointestinal Cancers Symposium.¹

Results showed that the pCR rate in the intention-to-treat (ITT) population given camrelizumab with nab-paclitaxel and cisplatin (n = 132) was 28.0% (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 translated to a 23.5% difference between the camrelizumab/nab-paclitaxel/cisplatin and chemotherapy-alone arms (95% CI, 15.1%-32.0%; P <.0001) and a 10.9% difference between the camrelizumab/paclitaxel/cisplatin and chemotherapy-alone arms (95% CI, 3.7%-18.1%; P = .0034). The odds ratios were 8.11 (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, of the Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, 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.2

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 T3N0M0). They were required to have an ECOG performance status of 0 or 1 and could not have received prior treatment.

Patients were randomized 1:1:1 to receive camrelizumab plus nab-paclitaxel and cisplatin every 3 weeks for 2 cycles, followed by surgery, and subsequent 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 subsequent surveillance (group C). 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 III 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 = 14) or surgery intolerability (n = 4). In group B, 125 patients received 2 cycles of therapy; 14 patients did not undergo surgery due to patient refusal (n = 4), surgery intolerability (n = 3), preoperative death (n = 1), or other (n = 6). Finally, in group C, 122 patients completed 2 cycles of therapy; 22 patients did not undergo definitive surgery due to patient refusal (n = 12), lost to follow-up (n = 1), or other (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 female. A total 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 III disease (71.3%). Three-fourths of patients had less than 10% PD-L1 tumor proportion score (TPS; 75.2%), and 78.5% had a PD-L1 combined positive score (CPS) of 1 or greater (78.5%).

Additional data showed that the camrelizumab/nab-paclitaxel/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 38.3% difference (95% CI, 27.4%-49.3%) between arms A and C and a 15.4% difference (95% CI, 4.7%-26.2%) between arms B and C, with ORs of 5.51 (95% CI, 3.18-9.56) and 2.19 (95% CI, 1.25-3.84), respectively.

In group A, the tumor regression grade (TRG) 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%, 31.0%, 29.3%, and 1.7%, respectively, and 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 3 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%). Additionally, most had total two-field as their lymph node dissection extent in 85.1%, 86.2%, and 79.6% of patients, respectively. 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%; 92.2%). One patient each in groups B and C underwent reoperations. In group A, 1 patient died within 30 days and 2 within 90 days; 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 32.0% 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 ≥3, 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 group A, B, and C, respectively. TEAEs leading to discontinuation of camrelizumab occurred in 0.8% and 0.8% of those in groups A and B. Chemotherapy discontinuation due to TEAEs occurred in 3.0% of those in group A, 3.8% of those in group B, and 0.8% of those in group C. One TEAE led to death, and this occurred in group B.

Grade 3 or higher preoperative treatment-related adverse effects (TRAEs) 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 B had TRAEs that led to camrelizumab discontinuation; 4 patients in arm A, 5 in arm B, and 1 in arm C experienced TRAEs that led to chemotherapy discontinuation. One patient in arm B had a TRAE that led to death. Serious adverse effects (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

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