Can Keytruda (pembrolizumab) improve life expectancy in patients with metastatic breast cancer?

Keytruda (Pembrolizumab) and Life Expectancy in Metastatic Breast Cancer

Keytruda (pembrolizumab) plus chemotherapy significantly prolongs life expectancy in metastatic triple-negative breast cancer, but only for patients whose tumors express PD-L1 with a combined positive score (CPS) ≥10, improving median overall survival from 16.1 months to 23.0 months (HR 0.73, P=0.0185). 1, 2

Critical Patient Selection Requirements

PD-L1 testing is mandatory before considering pembrolizumab for metastatic breast cancer. 1, 3 The following criteria must be met:

• Tumor type: Hormone receptor-negative AND HER2-negative (triple-negative) breast cancer only 1
• PD-L1 status: CPS ≥10 using the FDA-approved 22C3 companion assay specifically 1, 3
• Treatment line: First-line therapy for metastatic disease (untreated in the metastatic setting) 1, 2, 4
• Disease timing: Metastatic disease must have developed de novo OR at least 12 months after completion of neoadjuvant/adjuvant chemotherapy 3

Survival Benefits by PD-L1 Expression Level

CPS ≥10 (Recommended Population)

• Median overall survival: 23.0 months with pembrolizumab-chemotherapy vs 16.1 months with chemotherapy alone (6.9-month improvement) 2
• Hazard ratio for death: 0.73 (95% CI 0.55-0.95, P=0.0185) 2
• Median progression-free survival: 9.7 months vs 5.6 months (HR 0.65, P=0.0012) 1, 4

CPS ≥1 (Not Statistically Significant)

• Median overall survival: 17.6 months vs 16.0 months (HR 0.86, P=0.1125, not significant) 2
• Median progression-free survival: 7.6 months vs 5.6 months (HR 0.74, P=0.0014, did not meet prespecified statistical threshold) 1, 4

Overall Population (Intention-to-Treat)

• Median overall survival: 17.2 months vs 15.5 months (HR 0.89, significance not tested) 2

When Pembrolizumab Does NOT Prolong Life Expectancy

Pembrolizumab monotherapy (without chemotherapy) does not improve survival in metastatic triple-negative breast cancer, even in PD-L1-positive patients. 1, 5 The KEYNOTE-119 trial demonstrated:

• Second/third-line monotherapy: No survival benefit in any PD-L1 subgroup 1, 5
• CPS ≥10 patients: Median OS 12.7 months vs 11.6 months with chemotherapy (HR 0.78, P=0.057, not significant) 1, 5
• Overall population: Median OS 9.9 months vs 10.8 months with chemotherapy (HR 0.97) 1, 5

Non-Triple-Negative Breast Cancer

Pembrolizumab should NOT be used for hormone receptor-positive or HER2-positive metastatic breast cancer outside clinical trials. 3 There is no evidence supporting survival benefit in these subtypes in routine clinical practice. 3

Treatment Regimen Specifics

Pembrolizumab must be combined with chemotherapy in the first-line metastatic setting: 1, 2

• Pembrolizumab dose: 200 mg IV every 3 weeks 1, 2
• Chemotherapy options: Nab-paclitaxel, paclitaxel, OR gemcitabine-carboplatin (investigator's choice) 1, 2, 4
• Duration: Continue until disease progression or unacceptable toxicity 2, 4

Safety Profile

Grade 3-5 treatment-related adverse events occur in 68% of patients receiving pembrolizumab-chemotherapy vs 67% with chemotherapy alone. 1

• Most common severe toxicities: Neutropenia (30%), anemia (16%), with similar rates between groups 1
• Immune-mediated adverse events: Occur in 26% (any grade) and 5% (grade 3+) of pembrolizumab-treated patients 1
• Treatment-related deaths: <1% in pembrolizumab-chemotherapy group 2, 4
• Contraindications: Severe autoimmune disease, organ transplantation, or conditions precluding immunotherapy 6

Critical Pitfalls to Avoid

Do not use pembrolizumab without proper PD-L1 testing using the specific 22C3 assay. 1, 3 Different assays (such as SP142 for atezolizumab) are not interchangeable and use different scoring systems. 1, 3

Do not prescribe pembrolizumab monotherapy for metastatic triple-negative breast cancer expecting survival benefit. 1, 5 The combination with chemotherapy is essential for efficacy. 1, 2

Do not use pembrolizumab in patients with CPS <10 expecting overall survival benefit. 2 While progression-free survival may show modest improvement in CPS 1-9 patients, this did not translate to statistically significant or clinically meaningful overall survival benefit. 2

Verify the disease-free interval if the patient received prior neoadjuvant/adjuvant chemotherapy. 3 Pembrolizumab is only indicated if at least 12 months have elapsed since completion of prior therapy. 3