What is the first line of immunotherapy?

From the Guidelines

First-line immunotherapy is recommended for patients with advanced squamous cell lung cancer (SqCLC) and PD-L1 expression ≥50%, with pembrolizumab being the preferred option, as supported by the NCCN guidelines 1. When considering first-line treatment for SqCLC, the following factors are crucial:

• PD-L1 expression status
• Performance status (PS)
• Age
• Comorbidities For patients with PD-L1 expression ≥50%, pembrolizumab monotherapy is the standard first-line approach, as it has shown significant improvement in overall survival (OS) compared to standard chemotherapy 1. In contrast, for patients with PS 0-1 and without PD-L1 expression ≥50%, platinum-based doublet chemotherapy is the mainstay of first-line treatment, as recommended by the NCCN, ASCO, and ESMO guidelines 1. It is essential to note that treatment selection depends on cancer type, biomarker status, and patient-specific factors, including performance status and comorbidities. The use of immune checkpoint inhibitors, such as pembrolizumab, nivolumab, and atezolizumab, has transformed the therapeutic landscape of thoracic malignancies, offering unprecedented 5-year OS rates and long-term survival benefits for patients with NSCLC, particularly those with PD-L1 expression 1. Patients receiving immunotherapy should be monitored for immune-related adverse events, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions, which may require corticosteroid treatment and temporary immunotherapy interruption 1.

From the FDA Drug Label

The efficacy of KEYTRUDA in combination with fluoropyrimidine- and platinum-containing chemotherapy was investigated in KEYNOTE-859 (NCT03675737), a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 1579 patients with HER2-negative advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for metastatic disease.

A statistically significant improvement in OS, PFS, and ORR was demonstrated in patients randomized to KEYTRUDA in combination with chemotherapy compared with placebo in combination with chemotherapy at the time of a pre-specified interim analysis of OS.

First-line immunotherapy with pembrolizumab (KEYTRUDA) in combination with chemotherapy is a viable treatment option for certain types of cancer, including:

• HER2-negative advanced gastric or GEJ adenocarcinoma 2
• Metastatic or unresectable, recurrent HNSCC 2
• Malignant pleural mesothelioma 2

Key findings include:

• Statistically significant improvement in OS, PFS, and ORR in patients receiving pembrolizumab in combination with chemotherapy compared to those receiving chemotherapy alone or placebo in combination with chemotherapy.
• Pembrolizumab can be administered in combination with various chemotherapy regimens, including fluoropyrimidine- and platinum-containing chemotherapy.

From the Research

First-Line Immunotherapy for Non-Small Cell Lung Cancer

• Immunotherapy has become a crucial component in the treatment of non-small cell lung cancer (NSCLC), with immune checkpoint inhibitors (ICIs) being used as first-line treatment 3, 4, 5.
• The use of ICIs, such as pembrolizumab and atezolizumab, has shown improved overall survival and radiological responses in patients with high programmed death-ligand 1 (PD-L1) expression 3.
• For patients with low or no PD-L1 expression, a combination of PD-1/PD-L1 ICIs with platinum doublet chemotherapy is recommended, as it has shown greater benefits in overall survival and radiological responses compared to chemotherapy alone 3, 4.
• However, combining immunotherapy with chemotherapy can lead to higher toxicity, and the cost of ICIs can be a barrier to treatment for some patients 3, 4.

Patient Selection and Biomarkers

• Patient selection is crucial in determining the effectiveness of first-line immunotherapy, with factors such as PD-L1 expression, tumor histology, and tumor mutation burden being considered 5, 6.
• Biomarkers, such as PD-L1 expression and tumor mutation burden, can help predict which patients are likely to respond to immunotherapy 5, 6.
• Perfecting patient selection is an ongoing challenge, and further research is needed to identify the most effective biomarkers and treatment strategies 6.

Combination Therapies and Future Directions

• Combination therapies, such as nivolumab plus ipilimumab, have shown significant antitumor responses in various cancer types, including NSCLC 7.
• However, combination therapies can also increase the risk of immune-related adverse events, and further research is needed to identify optimal prognostic biomarkers and management strategies 7.
• Ongoing trials are testing novel immune blockade agents and combinatorial approaches, aiming to improve patient outcomes and tailor treatment to individual needs 6.