PAPILLON: Amivantamab Plus Chemotherapy in Patients With NSCLC Positive for EGFR Mutations

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Expert insights on the treatment of patients with non–small cell lung cancer positive for EGFR mutations and what the PAPILLON study seeks to address.

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.

EGFR exon 20 insertions are rare, comprising about 5% to 10% of EGFR mutations and 1% of non–small cell lung cancer. Standard EGFR tyrosine kinase inhibitors like osimertinib are ineffective for exon 20–mutated lung cancer due to steric hindrance preventing drug binding.

Mobocertinib initially showed promise but failed to improve outcomes over chemotherapy in a phase 3 trial, leading to its removal from clinical use. More recently, the antibody-drug conjugate amivantamab demonstrated response rates around 40% in exon 20-inserted NSCLC.

The phase 3 PAPILLON trial of amivantamab plus chemotherapy vs chemotherapy alone as first-line treatment was recently presented and published, nearly doubling progression-free survival from 6 to 7 months with chemotherapy alone to 11.5 to 12 months with amivantamab plus chemotherapy, with a hazard ratio under 0.4. This establishes a new standard of care for this patient population.

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

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