Treatment Decision-Making for Patients With EGFR+ NSCLC

Opinion
Video

An expert on EGFR+ non–small cell lung cancer discusses factors that influence treatment decisions.

Case: A 73-Year-Old Man with EGFR+ NSCLC

Clinical Presentation:

  • 73-year-old man initially presents with complaints of a persistent nonproductive cough, dyspnea on mild exertion, and an unintentional 10 lb. weight loss over prior 3 months

Past Medical History:

  • Coronary Artery Disease: treated with rosuvastatin 20 mg QD.
  • Hypertension, controlled on ARB QD.
  • Hyperlipidemia, treated with atorvastatin 20 mg QD.
  • COPD, maintained on triple inhalation therapy BID.

Social History:

  • Retired high school teacher; married with 2 adult children.
  • 50 pack-year smoking history: quit tobacco habit 5 years previously

Initial Clinical Workup and Diagnosis:

Physical Examination

  • Ambulatory but no longer drives and is capable of self-care without assistance.
  • Height: 5’10”; Weight:78 kg (172 lbs.)
  • ECOG PS: 1
  • Diminished breath sounds auscultated over right upper lobe.

Pulmonary Function Tests

  • FEV1 2.1 L (68% predicted) indicative of moderate obstruction.

Imaging Studies:

  • Chest CT: showed a 4.2 x 3.1 cm spiculated mass in the right upper lobe with suspected hilar lymph node involvement.
  • PET Scan: confirms hypermetabolic right hilar and subcarinal lymph nodes activity suggestive of malignancy.
  • MRI of Abdomen and Brain and Tech99 Bone Scintigraphy: no evidence of metastases.

Diagnostic Procedure:

  • Bronchoscopy with Biopsy: gross appearance of specimen obtained from right upper lobe consistent with adenocarcinoma of the lung.
    • Histopathology: confirms lung adenocarcinoma (Grade 2; pT2b pN1 [2/17 lymph nodes positive]; V0 R0), with partially papillary and partially tubular morphology.

Neoadjuvant Therapy and Surgical Resection:

  • Patient receives 4 cycles of cisplatin + pembrolizumab + pemetrexed.
  • He tolerated the regimen well with manageable episodes of fatigue, nausea, and sporadic neuropathy of the bilateral upper extremities.
  • Post-Treatment Restaging PET Scan: showed a good partial response.
  • Surgical Resection:
    • Lobectomy of the RUL with hilar and mediastinal lymphadenectomy via video-assisted thoracoscopic surgery (VATS).

Surgical Pathology Report:

  • ypT2aN1 (3/16 lymph nodes positive) with negative margins; Stage IIa
    • Adjuvant RT was recommended, but the patient declined.

Six Months Later:

  • Patient returns to his oncologist with complaints of recurrent, mid-to-low back pain.
  • Post-Operative Chest CT: displays scattered pulmonary nodules suspicious for metastatic disease progression.
  • Thoraco-lumbar MRI: negative for bony metastases.

Second Line Systemic Therapy:

  • Amivantamab was initiated with a weekly, weight-based infusion x4w(split dose, Days 1-2, Week 1), and thereafter q2w.
  • The patient developed a minor infusion reaction on day 1 of therapy, which resolved with application of cool compresses to the site and acetaminophen, 500 mg PO q4h, prn.

Repeat Imaging at 8 Weeks:

  • The patient experienced a good partial response.
    • He will continue to be followed regularly by his oncologist.

This is a video synopsis/summary of a Case-Based Peer Perspectives featuring Joshua K. Sabari, MD.

Sabari discusses deciding between the treatment options of osimertinib monotherapy, osimertinib plus chemotherapy (FLAURA2 trial), and amivantamab plus lazertinib (MARIPOSA trial) for frontline EGFR-mutated non-small cell lung cancer (NSCLC).

Considerations include patient factors like age, comorbidities, performance status, and toxicity tolerance. Osimertinib alone may be preferred for older, frailer patients to limit toxicity and visits. The amivantamab plus lazertinib combination could be utilized in younger, fitter patients due to the dual EGFR- and MET-targeting approach and immune activation.

For brain metastases, the MARIPOSA-2 data for EGFR patients pretreated with a tyrosine kinase inhibitor showed no additional central nervous system benefit from adding lazertinib to amivantamab plus chemotherapy. However, the MARIPOSA trial showed that upfront lazertinib may contribute to central nervous system control. Comparisons to FLAURA2 are difficult since routine brain imaging differed between trials.

Patient selection and balancing efficacy and toxicity are important when deciding between these emerging frontline options for eligible patients with EGFR-mutated NSCLC.

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

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