Camrelizumab vs Placebo in Combination With Chemotherapy as Neoadjuvant Treatment in Patients With Early or Locally Advanced Triple-Negative Breast Cancer: The CamRelief Randomized Clinical Trial

Abstract

Importance: Preferred neoadjuvant strategies for early or locally advanced triple-negative breast cancer include a 4-drug chemotherapy regimen containing anthracyclines, cyclophosphamide, taxanes, and platinum. Blockade of the programmed death receptor 1/ligand-1 (PD-1/PD-L1) pathway may improve efficacy of classic neoadjuvant chemotherapy. Camrelizumab, an anti-PD-1 antibody, has showed antitumor activity in advanced triple-negative breast cancer.

Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy for patients with early or locally advanced triple-negative breast cancer.

Design, setting, and participants: This randomized, double-blind, phase 3 trial enrolled patients from 40 hospitals in China between November 25, 2020, and May 12, 2023 (data cutoff: September 30, 2023). A total of 441 eligible patients were enrolled.

Interventions: Patients were randomized in a 1:1 ratio to receive either camrelizumab 200 mg (n = 222) or placebo (n = 219) combined with chemotherapy every 2 weeks. The chemotherapy included nab-paclitaxel (100 mg/m2) and carboplatin (area under the curve, 1.5) on days 1, 8, and 15 in 28-day cycles for the first 16 weeks followed by epirubicin (90 mg/m2) and cyclophosphamide (500 mg/m2) every 2 weeks for 8 weeks.

Main outcomes and measures: The primary end point was pathological complete response (defined as no invasive tumor in breast and lymph nodes [ypT0/Tis ypN0]).

Results: Among 441 females randomized (median age, 48 years), the median (range) follow-up duration from randomization was 14.4 (0.0-31.8) months. Pathological complete response was achieved in 126 patients (56.8% [95% CI, 50.0%-63.4%]) in the camrelizumab-chemotherapy group and 98 patients (44.7% [95% CI, 38.0%-51.6%]) in the placebo-chemotherapy group (rate difference, 12.2% [95% CI, 3.3%-21.2%]; 1-sided P = .004). In the neoadjuvant phase, adverse events of grade 3 or higher occurred in 198 patients (89.2%) in the camrelizumab-chemotherapy group and 182 (83.1%) in the placebo-chemotherapy group; serious adverse events occurred in 77 patients (34.7%) in the camrelizumab-chemotherapy group and 50 (22.8%) in the placebo-chemotherapy group, with fatal adverse events occurring in 2 patients (0.9%) in the camrelizumab-chemotherapy group.

Conclusions and relevance: Among patients with early or locally advanced triple-negative breast cancer, the addition of camrelizumab to neoadjuvant chemotherapy significantly improved pathological complete response.

Trial registration: ClinicalTrials.gov Identifier: NCT04613674.

Figure 1.. Treatment Schema

Patients were randomized in a 1:1 ratio and stratified by clinical stage (II vs III) and programmed death ligand-1 combined positive score (<10 vs ≥10). All study drugs were administered intravenously. AUC indicates area under the curve; TNBC, triple-negative breast cancer.

Figure 2.. Randomization and Flow of Trial Participants

Median (range) follow-up duration from randomization was 14.7 (0.0-31.0) months in the camrelizumab-chemotherapy group and 13.8 (0.5-31.8) months in the placebo-chemotherapy group. One patient in the camrelizumab-chemotherapy group withdrew after day 1, with a follow-up of 0.0 months after rounding. TNBC indicates triple-negative breast cancer. ^aThe screening procedure was delayed due to the COVID-19 pandemic, and the patient was deemed medically unsuitable for postponed treatment by the investigator. ^bPatients were not required to complete all neoadjuvant treatments to proceed to the operation. Patients who did not undergo surgery were imputed as nonresponders for the primary end point of pathological complete response.

Figure 3.. Pathological Complete Response (pCR) in the Overall Population and Across Predefined Baseline Subgroups

All patients who did not undergo surgery were imputed as nonresponders for the primary end point of pCR. CPS indicates combined positive score;; ECOG, Eastern Cooperative Oncology Group. ^aThe difference and 95% CIs were estimated using stratified Mantel-Haenszel weighted normal approximation for the overall population, and normal approximation for the subgroups. ^bIn the camrelizumab-chemotherapy group, 198 patients (89.2%) underwent surgery and pathological evaluation and 24 (10.8%) did not. In the placebo-chemotherapy group, 200 patients (91.3%) underwent surgery and 19 (8.7%) did not.