Camrelizumab/Chemo Could Represent New Neoadjuvant Option in Early or Locally Advanced TNBC

Triple-Negative Breast Cancer |
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The addition of camrelizumab to intensive chemotherapy in the neoadjuvant setting significantly improved pathologic complete response (pCR) rates vs chemotherapy alone and showed a trend toward improved survival in patients with early or locally advanced triple-negative breast cancer (TNBC), according to data from the phase 3 CamRelief study (NCT04613674).¹

The findings, which were presented at the 2024 San Antonio Breast Cancer Symposium and published in JAMA,² showed that in all patients, the camrelizumab regimen (n = 222) elicited a pCR rate of 56.8% vs 44.7% with chemotherapy alone (n = 219), translating to a 12.2% difference between the arms (95% CI, 3.3%-21.2%; 1-sided P = .0038).^1,2

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 III disease, camrelizumab plus chemotherapy (n = 79) induced a pCR rate of 49.4% vs 38.0% with chemotherapy alone (n = 79), translating to an 11.4% difference between the arms (95% CI, –4.0% to 26.8%). In those with node-positive disease who received the camrelizumab combination (n = 154) or chemotherapy alone (n = 157), the respective pCR rates were 57.8% and 42.7%, translating to a difference of 15.1% between the arms (95% CI, 4.13%-26.1%). Those with N3 positivity experienced a pCR rate of 52.2% with camrelizumab/chemotherapy (n = 23) vs 29.4% with chemotherapy alone (n = 17).

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.

“Our data support camrelizumab plus chemotherapy as a potential new neoadjuvant therapeutic option for treating early or locally advanced TNBC,” Zhi-Ming Shao, MD, 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 double-blind, randomized, phase 3 CamRelief study enrolled patients with stage II or III invasive TNBC defined as T2N0-1M0/T3N0M0 or T2N2-3M0/T3N1-3M0 who had not previously received systemic treatment and who had an ECOG performance status of 0 or 1. They underwent central assessment for PD-L1 expression.

Study participants were randomly assigned 1:1 to receive neoadjuvant camrelizumab or placebo at 200 mg on day 1 every 2 weeks paired with chemotherapy. Both arms received nab-paclitaxel (Abraxane) at 100 mg/m² plus carboplatin area under the curve 1.5 on days 1, 8, and 15 every 4 weeks for 16 weeks, followed by epirubicin at 90 mg/m² plus cyclophosphamide at 500 mg/m² on day 1 every 2 weeks for 8 weeks. Patients on both arms then went on to surgery, and for adjuvant treatment, they received camrelizumab at 200 mg every 2 weeks for up to 1 year plus standard of care (SOC) or SOC per clinical practice guidelines. Capecitabine was permitted in this phase.

Stratification factors included clinical stage (II vs III), and PD-L1 combined positive score (CPS; <10 vs ≥10).

The primary end point of the study was pCR rate (ypT0/Tis ypN0); 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 investigative arm, 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 control arm, these respective numbers were 198, 177, 173, and 200 patients.

A total of 222 patients in the camrelizumab combination arm and 219 patients in the chemotherapy-alone arm were included in the primary analysis. The data cutoff date was September 30, 2023, and the median follow-up time was 14.4 months (range, 0.0-31.8).

With regard to baseline characteristics, the median age across the camrelizumab/chemotherapy and placebo/chemotherapy arms was 49 years (range, 22-72) and 48 years (range, 22-75), respectively, and most patients had an ECOG performance status of 0 (87.4% vs 86.3%). In the camrelizumab arm, 14.0% of patients had a PD-L1 CPS under 1, 28.8% had a CPS of at least 1 but under 10, and 57.2% had a CPS of 10 or higher; in the chemotherapy-alone arm, these respective percentages were 12.8%, 29.2%, and 58.0%. Most patients across the arms had T2 disease (77.5% vs 77.2%) and stage II disease (64.4% vs 63.9%).

In the camrelizumab/chemotherapy arm, 30.6%, 43.2%, 15.8%, and 10.4% of patients had nodal involvement of N0, N1, N2, and N3, respectively; in the chemotherapy-alone arm, these respective rates were 28.3%, 46.1%, 17.8%, and 7.8%.

Investigators also evaluated tumor radiographic response rates before surgery. Camrelizumab plus chemotherapy led to an ORR of 87.4% (95% CI, 82.3%-91.5%) by investigator assessment and RECIST 1.1 criteria, 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% (95% CI, 77.0%-87.4%), 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 respective hazard ratios for EFS, DFS, and DDFS were 0.80 (95% CI, 0.46-1.42; P = .224), 0.58 (95% CI, 0.27-1.24; P = .0784), and 0.62 (95% CI, 0.29-1.33; P = .107).

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 adverse effects (AEs) occurred in 99.5% of those in the camrelizumab arm vs 100% of those in the chemotherapy-alone arm; they were grade 3 or higher for 89.2% and 83.1% of patients, respectively. Two patients in the camrelizumab/chemotherapy arm experienced grade 5 events in the form of interstitial lung disease (n = 1) and sudden cardiac death (n = 1). Serious AEs occurred in 34.7% and 22.8% of patients, respectively.

AEs led to treatment discontinuation of any drug in 18.5% of those in the investigative arm and 5.9% of those in the control arm. In the camrelizumab arm, AEs 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 arm were 2.3%, 2.3%, 3.7%, 2.3%, and 2.3%. Immune-related AEs were reported in 92.3% of those in the camrelizumab arm vs 16.4% of those in the chemotherapy-alone arm; these effects were grade 3 or higher in 9.5% and 0.5% of patients, respectively.

The most common hematological AEs of any grade experienced by at least 20% of patients in either the camrelizumab or chemotherapy-alone arms included decreased white blood cell count (94.1% vs 97.3%), decreased neutrophil count (93.7% vs 96.3%), anemia (89.6% vs 85.8%), decreased platelet count (64.0% vs 56.2%), and decreased lymphocyte count (30.6% vs 31.1%).

The most common non-hematological AEs experienced by at least 20% of patients in the investigative and control arms, respectively, comprised reactive capillary endothelial proliferation (87.8% vs 68.9%), increased alanine aminotransferase level (68.5% vs 63.9%), increased aspartate aminotransferase level (62.6% vs 63.9%), alopecia (57.2% vs 52.5%), nausea (45.5% vs 40.6%), vomiting (44.6% vs 44.3%), hypertriglyceridemia (36.0% vs 34.7%), pyrexia (29.7% vs 20.5%), urinary tract infection (27.9% vs 17.4%), hypercholesterolemia (25.2% vs 22.4%), increased gamma-glutamyltransferase (24.8% vs 24.7%), asthenia (23.9% vs 23.7%), and decreased weight (23.4% vs 11.0%).

Disclosures: Dr Shao had no financial relationships to disclose.

References

1. Shao Z-M, Chen L, Li H, et al. Neoadjuvant camrelizumab plus chemotherapy for early or locally advanced triple-negative breast cancer (CamRelief): a randomized, double-blind, phase 3 trial. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. Abstract GS-306.
2. Chen L, Li H, Zhang H, et al. 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. JAMA. Published online December 13, 2024. doi:10.1001/jama.2024.23560