Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer

Abstract

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer (mNSCLC), published in January 2023, was modified according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with oncogene-addicted mNSCLC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with oncogene-addicted mNSCLC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Korean Society for Medical Oncology (KSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with oncogene-addicted mNSCLC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, while respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies between the different regions of Asia.

Keywords: ESMO; Pan-Asian; guidelines; non-small cell lung cancer; treatment.

Figure 1

Treatment algorithm for stage IV mNSCLC after positive findings on molecular tests. Purple: general categories or stratification; blue: systemic anticancer therapy. ChT, chemotherapy; CPG, Clinical Practice Guideline; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; FDA, Food and Drug Administration; ICI, immune checkpoint inhibitor; MCBS, ESMO-Magnitude of Clinical Benefit Scale; mNSCLC, metastatic non-small-cell lung cancer; TKI, tyrosine kinase inhibitor. ^aPreferred option(s). ^bAn example of an approved third-generation TKI is osimertinib [I, A; ESMO-Magnitude of Clinical Benefit (ESMO-MCBS) v1.1 score: 4; ESCAT: I-A]. Lazertinib is another third-generation EGFR TKI that has been approved in Korea for the first-line treatment of patients with EGFR mutations. ^cExamples of approved first- and second-generation TKIs include erlotinib [I, B; ESMO-MCBS v1.1 score: 4; ESCAT: I-A], gefitinib [I, B; ESMO-MCBS v1.1 score: 4; ESCAT: I-A], afatinib [I, B; ESMO-MCBS v1.1 score: 5; ESCAT: I-A] and dacomitinib [I, B; ESMO-MCBS v1.1 score: 3; ESCAT: I-A]. ^dESMO-MCBS v1.1 was used to calculate scores for new therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms).^eNot EMA approved. ^fESCAT scores apply to alterations from genomic-driven analyses only. These scores were defined by the ESMO CPG guideline authors and validated by the ESMO Translational Research and Precision Medicine Working Group.^gEMA approved, not FDA approved. ^hPreferred over crizotinib in patients with brain metastases. ⁱFDA approved; application for EMA approval withdrawn by the manufacturer. ^jFDA approved; not EMA approved in first line. ^kNot EMA or FDA approved. ^lA parallel ESMO CPG on non-oncogene-addicted mNSCLC is available at: https://www.esmo.org/guidelines/guidelines-by-topic/lung-and-chest-tumours.^mFDA approved; not EMA approved. ⁿIf the patient has not been treated previously with a medicine that works in the same way as entrectinib. ^oFor patients who have no satisfactory alternative treatments.

Figure 2

Treatment algorithm for stage IV mNSCLC with EGFR-activating mutation. Purple: general categories or stratification; blue: systemic anticancer therapy; turquoise: combination of treatments or other systemic treatments; white: other aspects of management. cfDNA, cell-free DNA; ChT, chemotherapy; CPG, Clinical Practice Guideline; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of Molecular Targets; FDA, Food and Drug Administration; MCBS, ESMO-Magnitude of Clinical Benefit Scale; mNSCLC, metastatic non-small-cell lung cancer; NGS, next-generation sequencing; PD-L1, programmed death-ligand 1; PS, performance status; RT, radiotherapy; TKI, tyrosine kinase inhibitor. ^aPreferred option(s). ^bAn example of an approved third-generation TKI is osimertinib [I, A; ESMO-Magnitude of Clinical Benefit (ESMO-MCBS) v1.1 score: 4; ESCAT: I-A]. Lazertinib is another third-generation EGFR TKI that has been approved in Korea for the first-line treatment of patients with EGFR mutations. ^cRecommended treatment option for patients with a major uncommon, non-exon 20 insertion, sensitising EGFR mutation afatinib [I, B; ESMO-MCBS v1.1 score: 4; ESCAT: I-B] or osimertinib [III, B; ESCAT: I, B]. In China, sunvozertinib is approved for the treatment of patients with advanced or mNSCLC with an EGFR exon 20 insertion. ^dExamples of approved first- and second-generation TKIs include erlotinib [I, B; ESMO-MCBS v1.1 score: 4; ESCAT: I-A], gefitinib [I, B; ESMO-MCBS v1.1 score: 4; ESCAT: I-A], afatinib [I, B; ESMO-MCBS v1.1 score: 5; ESCAT: I-A] and dacomitinib [I, B; ESMO-MCBS v1.1 score: 3; ESCAT: I-A]. ^eESMO-MCBS v1.1 was used to calculate scores for new therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms).^{35 f}Not EMA approved. ^gESCAT scores apply to alterations from genomic-driven analyses only. These scores were defined by the ESMO CPG authors and validated by the ESMO Translational Research and Precision Medicine Working Group.^34hEMA approved, not FDA approved. ⁱPatients who have moderate radiological progression with ongoing clinical benefit may continue with EGFR TKIs [III, A]. ^jAn example of amivantamab-anti-PD-(L)1-bevacizumab-pemetrexed-platinum ChT is carboplatin-paclitaxel-atezolizumab-bevacizumab [III, B; ESMO-MCBS v1.1 score: 3; ESCAT: I-A]. ^kLazertinib is a third-generation EGFR TKI that has been approved in Korea for the treatment of patients with EGFR T790M mutations who have failed prior EGFR TKI therapy.

Figure 3

Treatment algorithm for stage IV mNSCLC with ALK translocation. Purple: general categories or stratification; blue: systemic anticancer therapy; turquoise: combination of treatments or other systemic treatments; white: other aspects of management. ALK, anaplastic lymphoma kinase; ChT, chemotherapy; CPG, Clinical Practice Guideline; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of Molecular Targets; FDA, Food and Drug Administration; MCBS, ESMO-Magnitude of Clinical Benefit Scale; mNSCLC, metastatic non-small-cell lung cancer; NGS, next-generation sequencing; RT, radiotherapy; TKI, tyrosine kinase inhibitor. ^aESMO-MCBS v1.1 was used to calculate scores for new therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms).^bPreferred option. ^cESCAT scores apply to alterations from genomic-driven analyses only. These scores were defined by the ESMO CPG authors and validated by the ESMO Translational Research and Precision Medicine Working Group.

Figure 4

Treatment algorithm for stage IV mNSCLC with ROS1 translocation. Purple: general categories or stratification; blue: systemic anticancer therapy; turquoise: combination of treatments or other systemic treatments; white: other aspects of management. ChT, chemotherapy; CPG, Clinical Practice Guideline; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of Molecular Targets; FDA, Food and Drug Administration; MCBS, ESMO-Magnitude of Clinical Benefit Scale; mNSCLC, metastatic non-small-cell lung cancer; RT, radiotherapy; TKI, tyrosine kinase inhibitor. ^aESMO-MCBS v1.1111 was used to calculate scores for new therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms).^bESCAT scores apply to alterations from genomic-driven analyses only. These scores were defined by the ESMO CPG guideline authors and validated by the ESMO Translational Research and Precision Medicine Working Group.^cPreferred over crizotinib in patients with brain metastases. ^dNot EMA approved.

Figure 5

Treatment algorithm for stage IV mNSCLC with BRAF V600 mutation. Purple: general categories or stratification; blue: systemic anticancer therapy; turquoise: combination of treatments or other systemic treatments; white: other aspects of management. ChT, chemotherapy, CPG, Clinical Practice Guideline; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of Molecular Targets; FDA, Food and Drug Administration; MCBS, ESMO-Magnitude of Clinical Benefit Scale; mNSCLC, metastatic non-small-cell lung cancer; RT, radiotherapy. ^aESMO-MCBS v1.1111 was used to calculate scores for new therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms).^bESCAT scores apply to alterations from genomic-driven analyses only. These scores were defined by the ESMO CPG authors and validated by the ESMO Translational Research and Precision Medicine Working Group.