Mechanism of Action of EGFR Inhibitors in NSCLC

Opinion
Video

Turning the focus to EGFR inhibitors, Sandip P. Patel, MD, discusses their mechanism action and the improved toxicity profile of next-generation inhibitors.

Case: A 60-Year-Old Woman with Early-Stage Non–Small Cell Lung Cancer

Initial presentation and Clinical Workup

  • Healthy 60-year-old Caucasian woman, 45 pack-year smoker, presented with a nonproductive cough
    • Physical exam revealed ECOG PS 0, BP: 120/93, HR: 74 bpm, BMI: 22
    • Pulm: lungs CTA bilaterally
    • Chest X-Ray: 5.5-cm right mass in right upper lobe
    • CT chest/abdomen: lobulated 5.5 x 5.1-cm mass in right upper lobe
    • Biopsy of Right Upper Lobe: adenocarcinoma, TTF1 (+) consistent with NSCLC
    • Labs are WNL; PET Imaging: negative for any lymph nodes or distant metastasis; Brain MRI: negative; PFTs: Normal

Treatment 

  • Mediastinoscopy with negative lymph nodes on frozen section, followed by right upper lobectomy without complications
  • Current ECOG PS remains 0
  • Histopathology reveals 5.5-cm tumor with negative margins; 0 nodes positive for malignancy (2R, 4R, 7, and 11R are all negative)
  • Patient is diagnosed with stage IIA (pT3N0M0) lung adenocarcinoma
  • Molecular testing shows EGFR exon (19del) and PD-L1 expression of 40%.
  • Post operation, the patient completes 4 cycles of adjuvant chemotherapy with cisplatin + pemetrexed. Her ECOG PS is 1.
  • Patient begins treatment with osimertinib. 20 months after initiating osimertinib, the patient reports headaches and worsening fatigue.
  • CT scans revealed 3 new liver lesions and Brain MRI visualized 1 new lesion.

This is a video synopsis/summary of a Case-Based Peer Perspectives featuring Sandip P. Patel, MD.

EGFR small-molecule inhibitors work by inhibiting the mutated, hyperactivated EGFR kinase in cancer cells. These oral targeted therapies essentially turn off an oncogenic signaling switch promoting uncontrolled growth. By shutting down aberrant EGFR activity, the drugs can induce cancer cell cycle arrest and death.

There are multiple generations of EGFR inhibitors. Later-generation agents have better central nervous system penetration to control brain metastases and are more selective, sparing wild-type EGFR inhibition that causes adverse effects like rash and diarrhea. By improving tolerability along with antitumor efficacy, these treatments can enhance patient quality of life compared to traditional chemotherapy.

Obtaining molecular profiling to identify EGFR mutations is thus critical to delivering optimal-quality, personalized therapy in non–small cell lung cancer (NSCLC). Pairing the right drug with the right patient molecular profile is imperative whether considering metastatic or localized disease settings. EGFR testing helps identify those who may derive profound benefit from genotype-directed therapy.

Video synopsis is AI-generated and reviewed by Targeted Oncology™ editorial staff.

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