Impact of PD-1 and PD-L1 Expression on Overall Survival in Patients With NSCLC and Melanoma

Source: Pharmacy Times, August 2024

The conventional treatment paradigms for melanoma and non–small cell lung cancer (NSCLC) have historically centered around surgery, radiation, and chemotherapy. Although potentially effective in the early stages of the disease, these methods often reach a therapeutic impasse when confronted with metastatic spread. The fields of melanoma and NSCLC, however, are witnessing a remarkable shift in treatment strategy, emphasizing the body’s immune response as a potent weapon against cancer’s formidable ability to spread and resist conventional therapies. Immunotherapy has emerged as a promising option, enhancing the specificity and potency of the immune system’s responses to these cancers.

Lung cancer, primarily NSCLC, accounts for the highest incidence and mortality rates among all cancers, with a significant proportion of patients diagnosed at advanced stages.4 Despite advancements in metastatic NSCLC treatment, resistance to targeted therapies remains challenging. However, therapies targeting the PD-1/PD-L1 pathway offer promising avenues for treatment. PD-L1 expression in NSCLC correlates with poorer outcomes, and selecting the appropriate FDA-approved PD-1/PD-L1 inhibitor for metastatic NSCLC can be difficult because of variations in patient and disease characteristics.5 The use of PD-1/PD-L1 inhibitors in advanced or metastatic NSCLC is based on PD-L1 expression levels (categorized as over 50% or ? 1%-49%). For PD-L1 over 50%, options include pembrolizumab (Keytruda; Merck Sharp & Dohme LLC), cemiplimab (Libtayo; Regeneron Pharmaceuticals, Inc), and atezolizumab (Tecentriq; Genentech, Inc) as monotherapy, whereas combination therapy involves nivolumab (Opdivo, Bristol Myers Squibb), cemiplimab, durvalumab (Imfinzi; AstraZeneca Pharmaceuticals LP), pembrolizumab, or atezolizumab. For PD-L1 expression (ranging from ? 1% to 49%), pembrolizumab may be used as monotherapy, and combination therapy options may include nivolumab, cemiplimab, durvalumab, pembrolizumab, or atezolizumab.

Arising from the malignant alteration of melanocytes, melanoma develops from neural crest cells. It can emerge in diverse locations where these cells migrate, primarily in the skin and central nervous system areas, such as the brain and gastrointestinal tract. Although stage 0 melanoma has a favorable 5-year survival rate of approximately 97%, this figure sharply declines to 10% for individuals diagnosed with stage IV metastatic disease.

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