What is the approach to personalized medicine in oncology for non-small cell lung cancer?

From the Guidelines

Personalized medicine in non-small cell lung cancer (NSCLC) involves tailoring treatment based on specific molecular and genetic characteristics of a patient's tumor, with the most recent guidelines recommending comprehensive molecular testing to identify actionable mutations such as EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, and KRAS, as well as PD-L1 expression levels 1. The approach to personalized medicine in NSCLC begins with comprehensive molecular testing of tumor tissue to identify actionable mutations.

• Key mutations to test for include EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, and KRAS, as well as PD-L1 expression levels.
• For patients with EGFR mutations, first-line treatments include osimertinib (80mg daily), erlotinib (150mg daily), or gefitinib (250mg daily) 1.
• ALK-positive patients typically receive alectinib (600mg twice daily), brigatinib (90mg daily for 7 days, then 180mg daily), or lorlatinib.
• ROS1-positive disease responds to crizotinib (250mg twice daily) or entrectinib, while BRAF V600E mutations are treated with dabrafenib plus trametinib.
• For patients with high PD-L1 expression (≥50%) without driver mutations, immunotherapy with pembrolizumab (200mg every 3 weeks) is standard 1.
• Those without targetable mutations typically receive combination chemotherapy (often platinum-based) with or without immunotherapy. This personalized approach significantly improves outcomes compared to conventional chemotherapy, with targeted therapies showing response rates of 60-80% and progression-free survival of 9-18 months in patients with corresponding mutations, as demonstrated in several phase III randomised trials 1. Regular monitoring for resistance mechanisms and sequential therapy planning are essential components of this approach, as most patients eventually develop resistance to initial targeted therapies.
• The T790M exon 20 substitution mutation is only rarely found in EGFR TKI-naive disease using standard techniques but is the most frequent cause of resistance to first- and second-generation EGFR TKIs (50%–60% of cases) 1.
• Cell-free DNA (cfDNA) blood testing is an acceptable approach to detect T790M at relapse but lacks sensitivity, so all patients with a negative blood test still require tissue biopsy 1.

From the FDA Drug Label

TAGRISSO is a prescription medicine used to treat adults with non-small cell lung cancer (NSCLC) that has certain abnormal epidermal growth factor receptor (EGFR) gene(s) Your healthcare provider will perform a test to make sure that TAGRISSO is right for you. Select patients for treatment with TAGRISSO based on the presence of a mutation as detected by an FDA-approved test.

The approach to personalized medicine in oncology for non-small cell lung cancer involves selecting patients for treatment with osimertinib (TAGRISSO) based on the presence of specific EGFR mutations, as detected by an FDA-approved test. This includes EGFR exon 19 deletions or exon 21 L858R mutations. The treatment is tailored to the individual patient's genetic profile, ensuring that they receive the most effective treatment for their specific type of cancer 2.

• Key considerations:
  • Genetic testing: Patients must undergo genetic testing to determine the presence of specific EGFR mutations.
  • FDA-approved test: The test used to detect EGFR mutations must be FDA-approved.
  • Treatment selection: Treatment with osimertinib (TAGRISSO) is selected based on the presence of specific EGFR mutations.
• Main idea: Personalized medicine in oncology for non-small cell lung cancer involves tailoring treatment to the individual patient's genetic profile.

From the Research

Personalized Medicine in Oncology for Non-Small Cell Lung Cancer

The approach to personalized medicine in oncology for non-small cell lung cancer (NSCLC) involves tailoring treatment to the individual patient's genetic profile and molecular characteristics of their tumor.

• Genetic Mutations: NSCLC patients harboring EGFR sensitive mutations may benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs) such as osimertinib, gefitinib, and erlotinib 3, 4.
• ALK Rearrangements: ALK rearrangements are a key driver mutation in NSCLC, and patients with this mutation may benefit from treatment with ALK inhibitors such as crizotinib, alectinib, and brigatinib 5, 4.
• Molecular Profiling: Comprehensive molecular profiling is essential to identify the genetic mutations and molecular characteristics of the tumor, which can inform treatment decisions 3, 6, 7.
• Targeted Therapies: Targeted therapies, such as TKIs, have improved outcomes for patients with NSCLC, particularly those with EGFR mutations or ALK rearrangements 3, 5, 4.
• Combination Therapies: Combination therapies, such as the use of chemotherapy and targeted therapies, may also be effective in treating NSCLC 4.
• Resistance Mechanisms: Understanding the mechanisms of resistance to targeted therapies is crucial to developing effective treatment strategies, as resistance is a major challenge in the treatment of NSCLC 3, 4.

Clinical Outcomes

The clinical outcomes for patients with NSCLC vary depending on the genetic mutations and molecular characteristics of the tumor.

• EGFR Mutations: Patients with EGFR mutations tend to have a higher frequency of lung, brain, and multiple extrapulmonary metastases 5.
• ALK Rearrangements: Patients with ALK rearrangements tend to have a longer median overall survival (OS) compared to those with EGFR mutations or wild-type tumors 5.
• Median Overall Survival: The median OS for patients with NSCLC varies depending on the genetic mutations and molecular characteristics of the tumor, with ALK-rearranged NSCLC tend to have a longer median OS compared to EGFR-mutated NSCLC 5.

Future Directions

The future of personalized medicine in oncology for NSCLC involves continued research into the genetic mutations and molecular characteristics of the tumor, as well as the development of new targeted therapies and combination therapies.

• Emerging Technologies: Emerging technologies, such as next-generation sequencing (NGS), are enabling the identification of new genetic mutations and molecular characteristics of NSCLC tumors 3, 6, 7.
• Clinical Trials: Clinical trials are ongoing to evaluate the efficacy and safety of new targeted therapies and combination therapies for NSCLC 4.
• Personalized Medicine: Personalized medicine is becoming increasingly important in the treatment of NSCLC, with treatment decisions being tailored to the individual patient's genetic profile and molecular characteristics of their tumor 6, 7.