Cases from the Community: Investigators Discuss the Optimal Management of EGFR-Mutated Non-Small Cell Lung Cancer — Symposium Proceedings

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of lung cancer.

LEARNING OBJECTIVES

• Counsel patients with newly diagnosed metastatic EGFR-mutated non-small cell lung cancer (NSCLC) regarding available therapeutic considerations, explaining the relevance of mutation type, symptomatology, sites and extent of metastases, prior therapeutic exposure and other factors.
• Appreciate the biological rationale for dual inhibition of MET and EGFR for patients with EGFR-mutated NSCLC, and understand recently presented data establishing the benefit of this strategy.
• Evaluate the documented efficacy of chemotherapy combined with EGFR-targeted therapy, and consider the current role of available approaches in both the front-line and relapsed/refractory settings for patients with metastatic NSCLC and EGFR mutations.
• Review published research findings with TROP2-directed antibody-drug conjugates for patients with metastatic NSCLC and EGFR mutations, and optimally incorporate these agents into treatment algorithms.
• Appraise the scientific rationale for the development of bispecific antibodies directed at PD-1 x VEGF, and reflect on the potential role of these agents in the management of EGFR-mutated NSCLC.
• Recall the biological rationale for the evaluation of various novel therapeutic approaches for patients with NSCLC and EGFR mutations.

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CREDIT DESIGNATION STATEMENT
Research To Practice designates this enduring material for a maximum of 2.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of this CME activity, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 2.25 Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, this program has been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of this CME activity, which includes participation in the evaluation component and a post-test, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, this program has been specifically designed for the following ABS practice area: complex general surgical oncology.

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HOW TO USE THIS CME ACTIVITY
To receive credit for this activity, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better, and fill out the evaluation.

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Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Prof Passaro has no relevant financial relationships to disclose. The following faculty reported relevant financial relationships with ineligible entities:

Dr Goldberg — Advisory Committees: AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BlossomHill Therapeutics, Daiichi Sankyo Inc, Johnson & Johnson, Lilly, Merck, Regeneron Pharmaceuticals Inc, Summit Therapeutics, Synthekine, Tubulis; Contracted Research: Adela, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Mirati Therapeutics Inc; Data and Safety Monitoring Boards/Committees: Daiichi Sankyo Inc. Dr Goldman — Consulting Agreements: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Genentech, a member of the Roche Group, Janssen Biotech Inc, Lilly, Pfizer Inc, Summit Therapeutics; Contracted Research: AbbVie Inc, Agenus Inc, Amgen Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Genentech, a member of the Roche Group, GSK, Janssen Biotech Inc, Lilly, Merck, Pfizer Inc, Puma Biotechnology Inc, RayzeBio, Summit Therapeutics, Tango Therapeutics. Dr Neal — Advisory Committees (Consulting and Advisory): AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Daiichi Sankyo, Genentech, a member of the Roche Group, Gilead Sciences Inc, GSK, Iovance Biotherapeutics, Janssen Biotech Inc, Lilly, Natera Inc, Novartis, Novocure Inc, Nuvation Bio Inc, Oxford BioTherapeutics, Pfizer Inc, Regeneron Pharmaceuticals Inc, Summit Therapeutics, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc; Contracted Research: Adaptimmune, BioNTech SE, Boehringer Ingelheim Pharmaceuticals Inc, Exelixis Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, GSK, Janssen Biotech Inc, Lilly, Merck, Novartis, Nuvalent, Revolution Medicines Inc, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc; Stock Options/Stock — Public Companies: SecondLook Health.

MODERATOR
Dr Sands — Consulting Agreements: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Catalyst Pharmaceuticals Inc, Daiichi Sankyo Inc, Fosun Pharma, Genentech, a member of the Roche Group, Gilead Sciences Inc, GSK, Lilly, Merck, Novartis, Pfizer Inc, PharmaMar, Sanofi; Contracted Research: Amgen Inc, Novartis.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, and Johnson & Johnson.

Release date: July 2026
Expiration date: July 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Prof Passaro

Cho BC et al. Enhanced versus standard dermatologic management with amivantamab-lazertinib in EGFR-mutated advanced NSCLC: The COCOON global randomized controlled trial. J Thorac Oncol 2025;20(10):1517-30. Abstract

Cho BC et al. Amivantamab plus lazertinib in atypical EGFR-mutated advanced non-small cell lung cancer (NSCLC): Results from CHRYSALIS-2. ASCO 2024;Abstract 8516.

Cho BC et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med 2024;391(16):1486-98. Abstract

Cho BC et al. Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial. ESMO 2023;Abstract LBA14.

Felip E et al. Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: A secondary analysis from MARIPOSA. Ann Oncol 2024;35(9):805-16. Abstract

Felip E et al. Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced non-small cell lung cancer (NSCLC) with biomarkers of high-risk disease: A secondary analysis from the phase 3 MARIPOSA study. ASCO 2024;Abstract 8504.

Hayashi H et al. Mechanisms of acquired resistance to first-line amivantamab plus lazertinib vs osimertinib: Updated analysis from MARIPOSA. World Conference on Lung Cancer 2025;Abstract PT1.03.06.

Jänne PA et al. Survival with osimertinib plus chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med 2026;394(1):27-38. Abstract

Jänne PA et al. CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor receptor-mutated advanced non-small-cell lung cancer. J Clin Oncol 2024;42(7):808-20. Abstract

Jänne PA et al. Osimertinib with/without platinum-based chemotherapy as first-line treatment in patients with EGFRm advanced NSCLC (FLAURA2). World Conference on Lung Cancer 2023;Abstract PL03.13.

Okuma Y et al. First-line osimertinib for previously untreated patients with NSCLC and uncommon EGFR mutations: The UNICORN phase 2 nonrandomized clinical trial. JAMA Oncol 2024;10(1):43-51. Abstract

Planchard D et al. Characterisation of benefit-risk by pemetrexed (pem) exposure in patients (pts) with EGFRm aNSCLC treated with 1L osimertinib (osi) + platinum-pem in FLAURA2. European Lung Cancer Congress 2025;Abstract 53P.

Planchard D et al. First-line osimertinib + chemotherapy versus osimertinib monotherapy in EGFRm advanced NSCLC: FLAURA2 final overall survival. World Conference on Lung Cancer 2025;Abstract PL02.06.

Planchard D et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med 2023;389(21):1935-48. Abstract

Sabari JK et al. Overall survival in EGFR-mutant advanced NSCLC treated with first-line osimertinib: A cohort study integrating clinical and biomarker data in the United States. J Thorac Oncol 2025;20(9):1268-78. Abstract

Spira AI et al. Preventing infusion-related reactions with intravenous amivantamab-results from SKIPPirr, a phase 2 study: A brief report. J Thorac Oncol 2025;20(6):809-86. Abstract

Yang JC-H et al. Amivantamab plus lazertinib vs osimertinib in first-line (1L) EGFR-mutant (EGFRm) advanced NSCLC: Final overall survival (OS) from the phase III MARIPOSA study. European Lung Cancer Congress 2025;Abstract 4O.

Yang JC-H et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med 2025;393(17):1681-93. Abstract

Yang JC-H et al. FLAURA2: Resistance, and impact of baseline TP53 alterations in patients treated with 1L osimertinib ± platinum-pemetrexed. World Conference on Lung Cancer 2024;Abstract MA12.03.

Dr Neal

Aredo JV et al. DLL3 immunohistochemical expression in neuroendocrine-transformed EGFR-mutant lung cancer and two cases of tarlatamab therapy. JTO Clin Res Rep. 2025;6(12):100913. Abstract

Califano R et al. Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutant advanced NSCLC after disease progression on osimertinib: Outcomes by osimertinib resistance mechanisms in MARIPOSA-2. ASCO 2025;Abstract 8639.

Cooper AJ et al. Multi-institution analysis of tarlatamab for the treatment of EGFR-mutant transformed small cell lung cancer. JCO Precis Oncol 2025;9. Abstract

Elamin YY et al. BLU-945 monotherapy and in combination with osimertinib (OSI) in previously treated patients with advanced EGFR-mutant (EGFRm) NSCLC in the phase 1/2 SYMPHONY study. ASCO 2023;Abstract 9011.

Fukuda S et al. Potential utility of a 4th-generation EGFR-TKI and exploration of resistance mechanisms-an in vitro study. Biomedicines 2024;12(7):1412. Abstract

Girard N et al. First-line subcutaneous amivantamab plus lazertinib in EGFR-mutated advanced NSCLC: Updated results from the PALOMA-2 study. European Lung Cancer Congress 2026;Abstract 13P.

Leighl NB et al. Subcutaneous amivantamab vs intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results, including overall survival (OS), from the global, phase 3, randomized controlled PALOMA-3 trial. ASCO 2024;Abstract LBA8505.

Lim SM et al. Subcutaneous (SC) after intravenous (IV) amivantamab in advanced NSCLC: Initial results from PALOMA-2. European Lung Cancer Congress 2025;Abstract 58P.

Nadal E et al. Subcutaneous (SC) amivantamab (ami) plus chemotherapy (chemo) in EGFR-mutant (EGFRm) advanced non-small cell lung cancer (NSCLC) after disease progression on osimertinib (osi). ESMO 2025;Abstract 1960P.

Parma M et al. Real-world efficacy and safety of tarlatamab in patients with relapsed extensive-stage small cell lung cancer. ASCO 2025;Abstract 8088.

Passaro A et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: Primary results from the phase III MARIPOSA-2 study. Ann Oncol 2024;35(1):77-90. Abstract

Peled N et al. COMPEL: Osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC and progression on first-line osimertinib. ESMO Open 2025;10(10):105807. Abstract

Scott SC et al. PALOMA-2: Subcutaneous amivantamab administered every 4 weeks plus lazertinib in first-line EGFR-mutated advanced NSCLC. World Conference on Lung Cancer 2025;Abstract MA08.05.

Dr Sands

Ahn M-J et al. A pooled analysis of datopotamab deruxtecan in patients with EGFR-mutated NSCLC. J Thorac Oncol 2025;20(11):1669-82. Abstract

Ahn M-J et al. Efficacy and safety of datopotamab deruxtecan in patients with previously treated EGFR-mutated advanced non-small cell lung cancer (NSCLC): Pooled analysis of TROPION-Lung01 and TROPION-Lung05. ESMO Asia 2024;Abstract LBA7.

Fang W et al. Sacituzumab tirumotecan in EGFR-TKI–resistant, EGFR-mutated advanced NSCLC. N Engl J Med 2026;394(1):13-26. Abstract

Pons-Tostivint E et al. Intracranial efficacy of datopotamab deruxtecan (Dato-DXd) in patients with advanced/metastatic NSCLC in TROPION-Lung01. World Conference on Lung Cancer 2025;Abstract OA10.01.

Zhao S et al. Sacituzumab tirumotecan in advanced non-small-cell lung cancer with or without EGFR mutations: Phase 1/2 and phase 2 trials. Nat Med 2025;31(6):1976-86. Abstract

Dr Goldman

Goldman JW et al. Ivonescimab vs placebo plus chemo, phase 3 in patients with EGFR+ NSCLC progressed with 3rd gen EGFR-TKI treatment: HARMONi. World Conference on Lung Cancer 2025;Abstract PL02.12.

Hong S-D et al. Izalontamab brengitecan (Iza-bren; BL-B01D1), a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, for patients with EGFR-mutated NSCLC: Pooled analysis of phase I and phase II trials. Ann Oncol 2026;37(6):813-24. Abstract

Dr Goldberg

Borgeaud M et al. Shifting paradigms in first-line treatment of EGFR-mutated NSCLC. healthbook TIMES Onco Hema 2025;25(3):66-71. Abstract

Fang W et al. Ivonescimab plus chemotherapy in non-small cell lung cancer with EGFR variant: A randomized clinical trial. JAMA 2024;332(7):561-70. Abstract

Goldberg SB et al. COPERNICUS, a pragmatic phase 2b study of first-line (1L) subcutaneous (SC) amivantamab (ami) + lazertinib (laz) with supportive care in EGFR-mutated advanced NSCLC: Early safety results. ASCO 2026;Abstract 8613.

Jänne PA et al. Survival with osimertinib plus chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med 2026;394(1):27-38. Abstract

Leal T et al. COPERNICUS, a pragmatic phase 2b study of subcutaneous (SC) amivantamab (ami) + chemotherapy (chemo) with enhanced dermatologic adverse event (AE) prophylaxis in EGFR-mutated advanced NSCLC: Interim results. ASCO 2026;Abstract 8614.

Leighl NB et al. Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory epidermal growth factor receptor-mutated non-small cell lung cancer: Primary results from the phase III PALOMA-3 study. J Clin Oncol 2024;42(30):3593-605. Abstract

Meric-Bernstam F et al. Prophylaxis, clinical management, and monitoring of datopotamab deruxtecan-associated oral mucositis/stomatitis. Oncologist 2025;30(3). Abstract

Riess JW et al. Osimertinib plus datopotamab deruxtecan in patients with EGFR-mutated advanced NSCLC after progression on first-line osimertinib: ORCHARD. Ann Oncol 2026;37(6):825-36. Abstract

Sands J et al. Analysis of drug-related interstitial lung disease (ILD) inpatients (pts) treated with datopotamab deruxtecan (Dato-DXd). ASCO 2024;Abstract 8623.

Sands J et al. Datopotamab deruxtecan vs docetaxel in patients with non-small cell lung cancer: Final overall survival from TROPION-Lung01. World Conference on Lung Cancer 2024;Abstract OA08.03.