Overview of Treatment Options for EGFR+ NSCLC

Opinion
Video

A medical oncologist provides an overview of treatment options available for patients with EGFR+ non–small cell lung cancer.

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.

This video features a continuation of the discussion of the case of a 73-year-old former 50 pack-year smoker with stage IIA resected EGFR mutant non–small cell lung cancer (NSCLC) who developed recurrent metastatic disease 6 months after surgery. The speaker notes upfront next-generation sequencing should have been done, as knowing about the patient’s exon 21 L858R EGFR mutation earlier could have impacted neoadjuvant treatment recommendations instead of the carboplatin, pemetrexed, and nivolumab combination.

Now that the EGFR mutation is identified, there are several frontline options for recurrent metastatic NSCLC with common EGFR mutations like exon 19 deletions and L858R, including osimertinib monotherapy, osimertinib plus chemotherapy, and the recent MARIPOSA trial data of amivantamab plus lazertinib. An MRI of the brain should also have been done at recurrence given the high central nervous system metastasis risk with EGFR-mutated NSCLC.

For frontline treatment of recurrent EGFR-mutant metastatic NSCLC, the standard of care remains osimertinib, an EGFR tyrosine kinase inhibitor with 18.9-month progression-free survival in the FLAURA trial. Patients with exon 19 deletion have better outcomes than patients with L858R, and co-mutations like TP53 may worsen prognosis.

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

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