From the Guidelines
For patients with EGFR exon 19 mutation positive non-small cell lung cancer (NSCLC) with PD-L1 expression >50%, the first-line treatment recommendation is an EGFR tyrosine kinase inhibitor (TKI) rather than immunotherapy. Osimertinib (80mg daily) is the preferred first-line EGFR TKI due to its superior efficacy and CNS penetration compared to earlier generation TKIs, as recommended by the NCCN guidelines 1. Alternative options include erlotinib (150mg daily), gefitinib (250mg daily), afatinib (40mg daily), or dacomitinib (45mg daily) 1. These medications should be continued until disease progression or unacceptable toxicity. Despite high PD-L1 expression, immune checkpoint inhibitors like pembrolizumab are not recommended as first-line therapy for EGFR-mutated NSCLC because they show lower efficacy than TKIs in this molecular subtype and may increase toxicity when used before or concurrently with TKIs 1. EGFR mutations drive cancer growth through constitutive activation of the EGFR signaling pathway, making targeted inhibition more effective than immunotherapy in this context. Some key points to consider in the treatment of EGFR exon 19 mutation positive NSCLC include:
- Regular monitoring for treatment response and common side effects (rash, diarrhea, paronychia) is essential, and dose modifications may be needed based on toxicity.
- Definitive local therapy has a role in the treatment of metastatic EGFR-positive NSCLC, particularly for patients with a limited number of initial sites of metastasis (oligometastasis) 1.
- For patients who experience disease progression after receiving first-line osimertinib, decisions about subsequent therapies are guided by disease symptoms as well as sites of progression, and may include chemotherapy or other targeted therapies 1.
From the Research
Treatment Options for EGFR Exon 19 Mutation Positive NSCLC with PD-L1 > 50%
- The first-line treatment of choice for patients with EGFR mutation-positive NSCLC is an EGFR tyrosine kinase inhibitor (TKI) 2.
- For patients with EGFR exon 19 deletion-positive NSCLC and high PD-L1 expression, a combination therapy with erlotinib and ramucirumab is being investigated as a potential treatment option 3.
- Elevated tumor PD-L1 expression is associated with poor outcomes of osimertinib monotherapy in previously untreated advanced NSCLC patients with EGFR mutation 4.
- However, another study found that PD-L1 expression is not uncommon in patients with metastatic NSCLC and EGFR mutations, but it does not significantly influence clinical outcomes in patients receiving standard initial treatment with EGFR-TKIs 5.
- The clinical benefit of osimertinib is unaffected by PD-L1 expression status, including in patients with PD-L1 expression ≥ 50% 6.
EGFR TKIs and PD-L1 Expression
- Afatinib, dacomitinib, and osimertinib have broader inhibitory profiles than the first-generation agents, gefitinib and erlotinib 2.
- The expression of PD-L1 on tumor cells plays an important role in predicting the efficacy of programmed cell death protein 1/PD-L1 inhibitors 5.
- PD-L1 staining thresholds of ≥ 1%, ≥ 25%, and ≥ 50% have been applied to determine the association between PD-L1 expression and clinical outcomes in patients with EGFRm advanced NSCLC 6.