Updates from MARIPOSA Trial in EGFR+ NSCLC

Opinion
Video

An overview of recent data from the MARIPOSA trial investigating amivantamab plus lazertinib in patients with EGFR-positive advanced 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 discussion on the recent phase 3 MARIPOSA trial results of the antibody-drug conjugate amivantamab plus the third-generation EGFR tyrosine kinase inhibitor lazertinib for the first-line treatment of EGFR-mutated non–small cell lung cancer (NSCLC). The trial compared amivantamab-lazertinib to osimertinib monotherapy and lazertinib monotherapy.

The amivantamab-lazertinib combination demonstrated nearly a 24-month median progression-free survival benefit over 16-17 months with osimertinib. Toxicities were manageable but increased, including more skin rash, venous thromboembolism requiring anticoagulation, and infusion reactions with amivantamab plus lazertinib.

Overall survival data is still immature, but a hazard ratio of 0.8 suggests potential for sustained benefit. Routine brain MRI was done and removing central nervous system progressions extended median progression-free survival to 28 to 29 months with the amivantamab-lazertinib combination.

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

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