Adding camrelizumab to presurgical chemotherapy significantly improved pathologic complete response (pCR) rates compared with chemotherapy alone in patients with early or locally advanced triple-negative breast cancer (TNBC), according to a phase 3 study.
Data from the phase 3 CamRelief study, presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) and published in JAMA Network, showed that in all patients, the camrelizumab regimen (222 patients) elicited a pCR rate of 56.8% versus 44.7% with chemotherapy alone (219 patients), translating to a 12.2% difference between the treatment groups.
Notably, pCR benefits with the addition of camrelizumab proved to be generally consistent across the subgroups examined, including higher-risk categories. Specifically, in patients with stage 3 disease, camrelizumab plus chemotherapy (79 patients) induced a pCR rate of 49.4% versus 38.0% with chemotherapy alone (79 patients), translating to an 11.4% difference between the arms. In those with node-positive disease who received the camrelizumab combination (154 patients) or chemotherapy alone (157 patients), the respective pCR rates were 57.8% and 42.7%, translating to a difference of 15.1% between the groups.
Early trends in event-free survival (EFS), disease-free survival (DFS) and distant disease-free survival complemented the pCR benefit observed with camrelizumab plus chemotherapy.
Glossary:
Pathologic complete response (pCR): patients who no longer show signs or symptoms of cancer.
Event-free survival (EFS): time patients remain free of cancer events, including progression or complications.
Disease-free survival (DFS): time patients live without signs or symptoms of cancer after treatment.
Distant disease-free survival: time after treatment when patients live without signs of cancer spreading to distant regions in the body.
ECOG performance status: a measurement of how independently patients can complete tasks. A score of 0 means they can complete tasks entirely independently and a score of 4 means they cannot complete tasks independently.
Objective response rate (ORR): percentage of patients who have a complete or partial response to treatment.
“Our data support camrelizumab plus chemotherapy as a potential new neoadjuvant (presurgical) therapeutic option for treating early or locally advanced TNBC,” Dr. Zhi-Ming Shao of Fudan University Shanghai Cancer Center and Key Laboratory of Breast Cancer, Shanghai Medical College, Fudan University, in China, said in a presentation of the data.
Approximately 15% of all breast cancer cases are triple-negative, and this disease subtype is known to have higher recurrence and poor survival outcomes. For those with early TNBC, the standard treatment approach has been an anthracycline paired with cyclophosphamide (AC), followed or preceded by a taxane. Dose-dense AC has proven effective in significantly reducing recurrence and mortality in these patients, according to Shao. However, the incorporation of platinum into the regimen has led to better pCRs. Despite the progress made to date, new approaches are needed to further improve outcomes.
The phase 3 CamRelief study enrolled patients with stage 2 or 3 invasive TNBC who had not previously received systemic treatment and who had an ECOG performance status of 0 or 1.
Study participants were randomly assigned to receive neoadjuvant camrelizumab or placebo paired with chemotherapy. Both treatment groups received nab-paclitaxel plus carboplatin, followed by epirubicin plus cyclophosphamide. Patients from both groups then went on to surgery, and for adjuvant (postsurgical) treatment, they received camrelizumab plus standard of care (SOC) or SOC per clinical practice guidelines. Xeloda (capecitabine) was allowed in this phase.
The primary end point of the study was pCR rate and secondary end points included EFS, DFS, DDFS, pre-surgery objective response rate (ORR) and safety.
Of the total 563 patients who were screened for eligibility, 441 patients were randomly assigned, including 222 patients assigned to camrelizumab plus chemotherapy and 219 assigned to chemotherapy alone. In the camrelizumab plus chemotherapy group, 196 patients completed treatment with camrelizumab plus nab-paclitaxel and carboplatin, 170 completed camrelizumab plus epirubicin and cyclophosphamide, 167 completed all prespecified neoadjuvant treatments and 198 underwent surgery. In the chemotherapy alone, these respective numbers were 198, 177, 173 and 200 patients.
A total of 222 patients in the camrelizumab combination group and 219 patients in the chemotherapy-alone group were included in the primary analysis. The data cutoff date was September 30, 2023, and the median follow-up time was 14.4 months.
Regarding baseline characteristics, the median age across the camrelizumab-chemotherapy and placebo-chemotherapy groups was 49 years and 48 years, respectively, and most patients had an ECOG performance status of 0 (87.4% versus 86.3%).
Camrelizumab plus chemotherapy led to an ORR of 87.4%, which comprised a complete response (CR) rate of 19.8% and a partial response (PR) rate of 67.6%; 3.2% of patients had stable disease (SD) and 1.4% experienced progressive disease (PD). A total of 8.1% of patients in this arm were not evaluable. Chemotherapy alone induced an ORR of 82.6%, which comprised CR and PR rates of 18.7% and 63.9%, respectively; the SD rate was 6.8% and the PD rate was 4.6%. A total of 5.9% of these patients were not evaluable.
The safety profile was manageable and consistent with the known profiles of each agent, Shao noted.
The mean number of treatment cycles with camrelizumab or placebo was 6.8 and 7.2, respectively. Any-grade side effects occurred in 99.5% of those in the camrelizumab group versus 100% of those in the chemotherapy-alone group. Side effects were grade 3 (severe) or higher for 89.2% and 83.1% of patients, respectively. Two patients in the camrelizumab-chemotherapy group experienced death in the form of interstitial lung disease (one patient) and sudden cardiac death (one patient). Serious side effects occurred in 34.7% and 22.8% of patients, respectively.
Side effects led to treatment discontinuation of any drug in 18.5% of those in the camrelizumab-chemotherapy group and 5.9% of those in the chemotherapy-alone group. In the camrelizumab group, side effects led to discontinuation of camrelizumab (9.9%), nab-paclitaxel (7.7%), carboplatin (10.8%), epirubicin (5.4%) and cyclophosphamide (5.4%); these respective percentages in the chemotherapy-alone group were 2.3%, 2.3%, 3.7%, 2.3% and 2.3%. Immune-related side effects were reported in 92.3% of those in the camrelizumab group versus 16.4% of those in the chemotherapy-alone group. These effects were grade 3 or higher in 9.5% and 0.5% of patients, respectively.
The most common blood-related side effects of any grade experienced by at least 20% of patients in either the camrelizumab or chemotherapy-alone groups included decreased white blood cell count (94.1% versus 97.3%), decreased neutrophil count (93.7% versus 96.3%), anemia (89.6% versus 85.8%), decreased platelet count (64% versus 56.2%) and decreased lymphocyte count (30.6% versus 31.1%).
The most common non-blood-related side effects experienced by at least 20% of patients in the camrelizumab and chemotherapy-alone groups, respectively, comprised reactive capillary endothelial proliferation (87.8% versus 68.9%), increased alanine aminotransferase level (68.5% versus 63.9%), increased aspartate aminotransferase level (62.6% versus 63.9%), alopecia (57.2% versus 52.5%), nausea (45.5% versus 40.6%), vomiting (44.6% versus 44.3%), hypertriglyceridemia (36% versus 34.7%), pyrexia (29.7% versus 20.5%), urinary tract infection (27.9% versus 17.4%), hypercholesterolemia (25.2% versus 22.4%), increased gamma-glutamyltransferase (24.8% versus 24.7%), asthenia (23.9% versus 23.7%) and decreased weight (23.4% versus 11%).
Reference:
“Neoadjuvant camrelizumab plus chemotherapy for early or locally advanced triple-negative breast cancer (CamRelief): a randomized, double-blind, phase 3 trial” by Zhi-Ming Shao, et al. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. Abstract GS-306.
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