Tarceva (erlotinib) and Tagrisso (osimertinib) are oral medications used to treat non-small cell lung cancer (NSCLC). Both are targeted therapies, designed to inhibit specific pathways that contribute to cancer growth. Their mechanisms, applications, and side effect profiles differ, making a comparison useful.
Targeting EGFR Mutations in Lung Cancer
Epidermal Growth Factor Receptor (EGFR) mutations are genetic changes found in a subset of non-small cell lung cancer cases. The EGFR protein, located on the surface of cells, normally helps regulate cell growth and division. When mutations occur in the gene that codes for this protein, it can lead to uncontrolled cell proliferation, contributing to cancer development.
Identifying these specific mutations is a foundational step before treatment with targeted therapies. Common activating mutations include deletions in exon 19 and the L858R substitution in exon 21. These mutations make cancer cells sensitive to therapies that block the EGFR pathway. Targeted therapy works by specifically interfering with the molecules involved in cancer growth and progression.
Tarceva Erlotinib
Tarceva (erlotinib) is a first-generation EGFR tyrosine kinase inhibitor (TKI). It functions by blocking the activity of the EGFR protein, inhibiting signals that promote cancer cell growth. Erlotinib is an oral, once-daily tablet.
Tarceva is approved for NSCLC patients with specific EGFR mutations, such as exon 19 deletions or L858R substitution. It has been used as a first-line treatment in some cases, and for patients who have previously received chemotherapy. Erlotinib can prolong progression-free survival and may also extend overall survival.
Common side effects include skin rash and diarrhea. The rash may resemble acne and can appear red, swollen, or crusty. Other reported side effects include decreased appetite, cough, fatigue, nausea, vomiting, and mild eye problems. More serious, though less common, side effects can involve lung changes, kidney or liver problems, and gastrointestinal perforation.
Tagrisso Osimertinib
Tagrisso (osimertinib) is a third-generation EGFR tyrosine kinase inhibitor (TKI). This medication is designed to irreversibly and selectively target EGFR TKI-sensitizing mutations and the T790M resistance mutation, while having less effect on wild-type EGFR. This selectivity helps address a common resistance mechanism that can develop with earlier-generation TKIs.
Tagrisso is approved as a first-line treatment for NSCLC patients with specific EGFR mutations, namely exon 19 deletions or L858R substitution. It is also indicated for patients who develop the T790M resistance mutation after previous TKI therapy. Osimertinib has improved brain penetration, beneficial for central nervous system metastases.
Common side effects include diarrhea, rash, dry skin, and nail changes. Nail changes can include alterations in shape, thickness, color, or the development of ridges. Other frequently reported side effects include musculoskeletal pain, mouth sores, fatigue, and cough. Serious, though less common, side effects can include heart problems like heart failure or abnormal heart rhythms, and lung inflammation.
Comparing Treatment Pathways
The distinction between Tarceva, a first-generation TKI, and Tagrisso, a third-generation TKI, influences treatment decisions in EGFR-mutated non-small cell lung cancer. Tagrisso’s main advantage is its effectiveness against the T790M resistance mutation, which can emerge after treatment with earlier-generation TKIs like Tarceva. This allows Tagrisso to remain effective even when cancer develops resistance to earlier treatments.
Tagrisso is preferred as a first-line treatment for common EGFR mutations (exon 19 deletions or L858R substitution) due to its superior efficacy and improved brain penetration for managing or preventing brain metastases. Clinical trials have shown that first-line osimertinib improved overall survival and progression-free survival compared to first-generation EGFR TKIs such as erlotinib, indicating a reduced risk of progression or death.
Tarceva may still be considered in specific situations, such as if Tagrisso is not available or if a patient’s mutation profile suggests it could be effective. However, the development of resistance, particularly the T790M mutation, often necessitates a switch to a third-generation TKI. Treatment decisions are individualized, depending on the specific EGFR mutation detected, the patient’s overall health, and prior treatment history. Comprehensive genomic testing guides these choices, ensuring the most appropriate targeted therapy is selected.