Key Takeaways on Treating Patients With EGFR+ NSCLC

Opinion
Video

Joshua K. Sabari, MD, offers key takeaways on treating patients with EGFR+ non–small cell lung cancer, highlighting the safety profile.

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 summarizes that patients want to live and live well, and most are willing to tolerate toxicity risks for potential survival benefit. While patient factors impact regimen selection, combination therapies with novel mechanisms of action are important to advance outcomes. All patients with lung cancer should have molecular profiling, including at early stages, because anyone can harbor targetable mutations.

Once an EGFR mutation is identified, mutation specifics matter: exon 19/L858R patients have better prognoses and more options than the rarer exon 20 insertions. Combinations like amivantamab-lazertinib in the MARIPOSA trial help exon 19/L858R patients, while amivantamab has become standard for first-line exon 20 mutated lung cancer based on the PAPILLON trial. More combinations utilizing new antibody-drug conjugates, T-cell engagers, and other novel agents with EGFR inhibitors represent promising future directions.

The key messages are to test all patients, understand the implications of specific mutations, have transparent discussions regarding benefits/risks, and sequence therapy appropriately to extend life and maintain quality.

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

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