Postoperative EGFR-TKI Therapy forContralateral Pulmonary Nodules in Patients With EGFR-Mutant NSCLC（ARMOR2501）

Summary

Background Synchronous multifocal primary lung cancer (sMPLC) presents a therapeutic challenge, particularly for bilateral lesions. While surgical resection is standard for unilateral sMPLC, bilateral surgery carries high perioperative risks. This study evaluates postoperative adjuvant therapy with almonertinib, a third-generation EGFR-TKI, to reduce secondary surgery rates by targeting residual contralateral lesions in EGFR-mutant NSCLC patients. Objective * Primary: Assess the secondary surgery rate within one year after three months of almonertinib therapy. * Secondary: Evaluate tumor response (ORR, EGFR-TKI response rate), survival outcomes (DFS, OS), treatment safety, and surgical feasibility post-therapy. Study Design * Phase: Single-arm, open-label, phase II trial. * Population: 32 patients with bilateral sMPLC (EGFR exon 19 deletion/L858R mutations) after unilateral resection. * Intervention: Oral almonertinib (110 mg/day) for three months, initiated 4-10 weeks post-surgery. * Endpoints: * Primary: Proportion requiring secondary surgery due to lesion persistence/progression. * Secondary: ORR (RECIST 1.1), DFS, OS, adverse events (CTCAE v5.0), and safety of delayed surgery. * Inclusion Criteria: * sMPLC diagnosis (MM/ACCP criteria), T1-2N0M0 primary lesion, residual contralateral nodules (≥8 mm, confirmed malignant). * ECOG 0-1, age 18-75 years, compliance with follow-up. * Exclusion Criteria: Metastasis, severe organ dysfunction, prior malignancies (5 years), or concurrent QT-prolonging drugs. Statistical Analysis * Sample size calculated (α=0.05, power=0.95) to detect a reduction in secondary surgery rate from 100% (baseline) to 90%, accounting for 10% dropout. * Survival analysis via Kaplan-Meier curves and Cox regression; descriptive statistics for response rates. Safety Monitoring • Adverse events graded by CTCAE v5.0, including interstitial lung disease (ILD), cardiac toxicity, and laboratory abnormalities. Dose adjustments (55 mg) or discontinuation mandated for grade ≥3 events. Ethics and Compliance * Conducted per Good Clinical Practice (GCP) and Declaration of Helsinki. * Informed consent required; independent review committee (IRC) evaluates imaging outcomes. Expected Outcomes * Almonertinib may reduce secondary surgery rates by suppressing residual lesions, supported by prior efficacy in NSCLC (median PFS: 19.3 months in AENEAS trial). * Results will inform postoperative management strategies for bilateral sMPLC. Timeline Enrollment and preliminary efficacy analysis to conclude by December 2025. Conclusion ARMOR2501 aims to validate almonertinib's role in minimizing repeat surgeries for EGFR-mutant sMPLC, balancing efficacy and safety. Successful outcomes could establish a novel adjuvant paradigm for high-risk patients.

Eligibility

Inclusion Criteria:

* 1）Patients diagnosed with sMPLC (according to MM/ACCP clinical criteria). Preoperative chest CT (1mm slice thickness) reveals multiple bilateral lesions, all meeting surgical criteria \[≥8mm (pure ground-glass nodules (GGNs) must be \>1cm) and unchanged after standard anti-inflammatory treatment\].

  2）Patients received standard anti-inflammatory treatment before surgery.

  3）The primary lesion in the operated lung is staged as T1-2N0M0.

  4）Patients have undergone surgical resection of one side of the lung, with pathology confirming adenocarcinoma and an EGFR-sensitive mutation (exon 19 deletion or exon 21 L858R point mutation).

  5）After unilateral resection, the contralateral lung must have at least one suspected malignant residual nodule \[≥8mm (pure GGNs must be \>1cm) and \<3cm, unchanged after standard anti-inflammatory treatment\], which must be confirmed as malignant by a qualified radiologist and thoracic surgeon.

  6）ECOG performance status (PS) score of 0-1.

Exclusion Criteria:

* 1）Patients with lymph node metastasis or distant metastasis.

  2）Patients with severe heart, lung, liver, or kidney dysfunction who cannot tolerate surgery.

  3）Patients with a history of other malignancies within five years (except effectively controlled basal cell carcinoma, cervical carcinoma in situ, ductal carcinoma in situ of the breast, papillary thyroid carcinoma, and superficial bladder tumors).

  4）Patients taking medications known to prolong the QTc interval or induce ventricular tachycardia who need to continue such medications during the study period.

  5）Patients with a history of interstitial lung disease (ILD) or drug-induced ILD.

  6）Patients with severe gastrointestinal dysfunction, diseases, or clinical symptoms that may affect drug intake, transport, or absorption.

  7）Patients with active hepatitis B, hepatitis C, or HIV infections.

  8）Pregnant or lactating women or women of childbearing potential who have not taken contraceptive measures.

  9）Patients with uncontrolled neurological or psychiatric disorders or mental illnesses.

  10）Patients participating in other clinical trials or expected to receive other anti-tumor treatments during this trial.

  11）Other conditions deemed unsuitable for the study by the investigators

Conditions3

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