PC03.01 Adjuvant Therapy for Resected NSCLC Harboring EGFR Mutation, Chemotherapy or Targeted Therapy - PROs

Abstract

Lung cancer is so far the leading cause of cancer death worldwide. Complete surgical resection remains the most effective approach for patients with early-stage non-small cell lung cancer (NSCLC). Patients with completely resected stage I NSCLC could have a 5-year survival of ∼80%, whereas it fails to ∼30%. Since 2003, adjuvant chemotherapy became the standard of care showing 4% absolute 5-year survival benefit compared to surgery alone [1]. Following randomized control trials revealed similar results [2-4], yet limited survival benefit, low therapeutic completed rate plus high toxicities rate may somehow hinder its clinical applicability. In the past decade, targeted therapies had achieved tremendous success in oncogene-driven advanced NSCLC showing both high efficacy and low toxicities [5]. As a matter of course, targeted therapy had its baby steps in early-stage NSCLC. However, no positive results were found in these trials which should probably be blame for large proportion of stage IB patients and incorrect detection methods for EGFR mutation. Besides, conservative trial design without head to head comparison could not fully address toxicities issues caused by chemotherapy. Precise target population seemed to be an essential key point to adjuvant targeted therapies and ADJUVANT as well as EVAN trial came into being [6, 7]. Although overall survival (OS) was not mature enough to measure, significantly prolonged disease-free survival (DFS) was observed in both trials along with better tolerability. Indeed, questioning around adjuvant targeted therapy has never been adjourned such as the optimal duration of targeted therapies, study design and lack of OS data. Ross et al brought up with an informative comment for ADJUVANT trial bringing the concept of MRD (molecular residual disease) into adjuvant treatment [8]. Based on the ctDNA testing after standard of care adjuvant chemotherapy, patients of high risk of recurrence will be given further treatments while observation for the others. It highlighted the significant role of discriminating beneficiaries from adjuvant targeted therapies instead of simply providing more efficient treatment modalities. Previous biomarker-based studies regarding adjuvant treatment among different tumor types [9, 10] had provided inspirational examples, and as well shown clinical feasibility and urgent need for personalized adjuvant treatment after complete surgical resection. For ADJUVANT trial, we established a comprehensive signature of genetic-features (MEDUSA) to guide personalized adjuvant treatment in EGFR-mutant stage II-III NSCLC. Results would be unleashed in upcoming ESMO meeting. Through utilizing multi-omics data, we could predict whether additional treatments, adjuvant chemotherapy only or observation would be adequate for each individual and provide optimal sequential treatments. Further translational researches and corresponding trials regarding resectable NSCLC should decipher the issues. Fortunately, several trials regarding dynamic monitoring postoperative ctDNA or genomic profile of primary cancer to guide sequential treatments are ongoing and the results should be expected. 1. Arriagada R, Bergman B, Dunant A et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004; 350: 351-360. 2. Winton T, Livingston R, Johnson D et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005; 352: 2589-2597. 3. Strauss GM, Herndon JE, 2nd, Maddaus MA et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol 2008; 26: 5043-5051. 4. Douillard JY, Rosell R, De Lena M et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol 2006; 7: 719-727. 5. Hirsch FR, Scagliotti GV, Mulshine JL et al. Lung cancer: current therapies and new targeted treatments. Lancet 2017; 389: 299-311. 6. Zhong WZ, Wang Q, Mao WM et al. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol 2018; 19: 139-148. 7. Yue D, Xu S, Wang Q et al. Erlotinib versus vinorelbine plus cisplatin as adjuvant therapy in Chinese patients with stage IIIA EGFR mutation-positive non-small-cell lung cancer (EVAN): a randomised, open-label, phase 2 trial. Lancet Respir Med 2018; 6: 863-873. 8. Ng TL, Camidge DR. Lung cancer's real adjuvant EGFR targeted therapy questions. Lancet Oncol 2018; 19: 15-17. 9. Sparano JA, Gray RJ, Makower DF et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2015; 373: 2005-2014. 10. Dienstmann R, Salazar R, Tabernero J. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients. J Clin Oncol 2015; 33: 1787-1796. Adjuvant therapy, EGFR-TKI, Lung cancer