Guideline Essentials: 2023 ESMO Recommendations on Management of Oncogene Addicted Metastatic Non-small Cell Lung Cancer

Guidelines Team, Medically Reviewed by Professor Sanjay Popat | Disclosures

Introduction

In 2023, the European Society for Medical Oncology (ESMO) published guidelines on the diagnosis, treatment, and follow up of patients with oncogene addicted and non-oncogene addicted metastatic non-small cell lung cancer (NSCLC).

This specialist Guidelines overview for secondary care oncologists outlines recommendations on the management of patients with advanced and metastatic oncogene addicted NSCLC.

Please refer to the full ESMO guidelines for all of the recommendations, rationale, and background information.

Related to This Summary:

For recommendations from the European Society of Medical Oncology (ESMO) on diagnosis, pathology, staging, risk assessment, and follow up of metastatic non-small cell lung cancer (NSCLC), see the Guidelines summary which covers both oncogene and non-oncogene addicted NSCLC
ESMO recommendations on the management of non-oncogene addicted metastatic NSCLC can be found on a separate Guidelines summary

Epidermal Growth Factor Receptor Mutated NSCLC

Table 1: Treatment Options for Epidermal Growth Factor Receptor Mutated NSCLC

Patient Group	Recommended Treatment Options
First-line Treatment Options
All patients with a sensitising EGFR mutation, irrespective of clinical parameters including gender, tobacco exposure, histology, and PS	Offer first-line treatment with EGFR TKIs Single-agent EGFR TKIs can be used as standard due to potential increase in toxicity, costs, and patient inconvenience as each additional treatment is added
Patients with activating EGFR mutation (exon 19 deletion or exon 21 L858R), particularly those who have CNS metastases	Osimertinib is preferable
Patients with a major uncommon, non-exon 20 insertion, sensitising EGFR mutation	Afatinib or osimertinib are options
Other first-line treatment options	Single agents: erlotinib, gefitinib, afatinib, and dacomitinib Gefitinib combined with carboplatin–pemetrexed EGFR TKIs combined with anti-angiogenic therapy, e.g. erlotinib–bevacizumab or erlotinib–ramucirumab
Continue with EGFR TKIs in patients with moderate radiological progression and ongoing clinical benefit
Progression and Treatment Resistance Options
Resistance to first-line first- or second-generation EGFR TKIs	Test for EGFR exon 20 T790M mutation from plasma cfDNA and/or tumour re-biopsy
T790M-positive resistance	Osimertinib as second line
T790M-negative resistance	Platinum-based ChT
Develops resistance to osimertinib	Genomic analysis by NGS (either tissue or cfDNA followed by tissue if no target found with cfDNA)
Progression on osimertinib	Platinum-doublet ChT; encourage clinical trial enrolment, particularly if a targetable resistance mechanism is identified
EGFR TKI failure, PS 0–1, and no contraindications for ICIs	Consider the combination of atezolizumab–bevacizumab–paclitaxel–carboplatin
Progression on EGFR TKIs and ChT	Consider single-agent ICIs only in these circumstances
NSCLC=non-small cell lung cancer; EGFR=epidermal growth factor receptor; PS=performance status; TKIs=tyrosine kinase inhibitors; CNS=central nervous system; cfDNA=cell-free DNA; ChT=chemotherapy; NGS=next generation sequencing; ICI=immune checkpoint inhibitor

Anaplastic Lymphoma Kinase Rearranged NSCLC

Table 2: Treatment Options for Anaplastic Lymphoma Kinase Rearranged NSCLC

Patient Group	Recommended Treatment Options
First line	Alectinib, brigatinib, or lorlatinib in preference to crizotinib or ceritinib
Progression on crizotinib; intolerance of crizotinib	Alectinib
Crizotinib resistance	Brigatinib and ceritinib are additional treatment options
Progression on second-generation ALK TKI	Lorlatinib is an option
Progression on lorlatinib	ChT with a platinum–pemetrexed-based combination is recommended Consider atezolizumab–bevacizumab–paclitaxel–carboplatin
NSCLC=non-small cell lung cancer; ALK=anaplastic lymphoma kinase; TKI=tyrosine kinase inhibitor; ChT=chemotherapy

ROS1 Rearranged NSCLC

Table 3: Treatment Options for ROS1 Rearranged NSCLC

Patient Group	Recommended Treatment Options
First line	Crizotinib or entrectinib Repotrectinib, if available, is an option
Brain metastases	Entrectinib, if available, is preferred to crizotinib
Progression on first-line crizotinib	Offer a newer-generation TKI, if available, or platinum-based ChT
TKI=tyrosine kinase inhibitor; ChT=chemotherapy

BRAF Mutations

Table 4: Treatment Options for BRAF V600 Mutations in Oncogene Addicted NSCLC

Patient Group	Recommended Treatment Options
First line	BRAF–MEK inhibition with dabrafenib–trametinib
No smoking history, received BRAF–MEK inhibition first line	Platinum-based ChT, with or without immunotherapy, second line
Smoking history, received BRAF–MEK inhibition first line	Consider immunotherapy with or without ChT (see Guideline Essentials on non-oncogene addicted mNSCLC)
NSCLC=non-small cell lung cancer; ChT=chemotherapy; mNSCLC=metastatic non-small cell lung cancer

Other Oncogenic Drivers

Table 5: Treatment Options for Other Oncogenic Drivers of NSCLC

Patient Group	Recommended Treatment Options
RET fusion-positive NSCLC	First line: selpercatinib or pralsetinib
MET amplification, NTRK gene fusion, HER2 mutation, and EGFR exon 20 mutation	First line: platinum-doublet ChT, with or without ICIs
MET exon 14 skipping mutation	First or second line: capmatinib or tepotinib
MET exon 14 skipping mutation, MET TKI not available	First line: platinum-doublet ChT, with or without ICIs
HER2 exon 20 mutations following previous first-line therapy	Trastuzumab–deruxtecan, if available
NTRK gene fusion with no satisfactory treatment options	Larotrectinib and entrectinib
KRAS G12C-mutated NSCLC	See first-line treatment for non-oncogene addicted mNSCLC
KRAS G12C-mutated NSCLC and progression on first-line monotherapy ICI	Platinum-doublet ChT
KRAS G12C-mutated NSCLC following failure of previous therapy	Sotorasib Adagrasib
NSCLC=non-small cell lung cancer; RET=rearranged during transfection; MET=mesenchymal epithelial transition; NTRK=neurotrophic tyrosine receptor kinase; HER2=human epidermal growth factor receptor 2; EGFR=epidermal growth factor receptor; ChT=chemotherapy; ICI=immune checkpoint inhibitor; TKI=tyrosine kinase inhibitor; KRAS=Kirsten rat sarcoma virus; mNSCLC=metastatic non-small cell lung cancer

Guideline Essentials: 2023 ESMO Recommendations on Management of Oncogene Addicted Metastatic Non-small Cell Lung Cancer

Disclosures

Introduction

Epidermal Growth Factor Receptor Mutated NSCLC

Table 1: Treatment Options for Epidermal Growth Factor Receptor Mutated NSCLC

Anaplastic Lymphoma Kinase Rearranged NSCLC

Table 2: Treatment Options for Anaplastic Lymphoma Kinase Rearranged NSCLC

ROS1 Rearranged NSCLC

Table 3: Treatment Options for ROS1 Rearranged NSCLC

BRAF Mutations

Table 4: Treatment Options for BRAF V600 Mutations in Oncogene Addicted NSCLC

Other Oncogenic Drivers

Table 5: Treatment Options for Other Oncogenic Drivers of NSCLC

References

UP NEXT

About

Membership

App

WebMD Network

Editions

Guideline Essentials: 2023 ESMO Recommendations on Management of Oncogene Addicted Metastatic Non-small Cell Lung Cancer

Disclosures

Introduction

Epidermal Growth Factor Receptor Mutated NSCLC

Table 1: Treatment Options for Epidermal Growth Factor Receptor Mutated NSCLC

Anaplastic Lymphoma Kinase Rearranged NSCLC

Table 2: Treatment Options for Anaplastic Lymphoma Kinase Rearranged NSCLC

ROS1 Rearranged NSCLC

Table 3: Treatment Options for ROS1 Rearranged NSCLC

BRAF Mutations

Table 4: Treatment Options for BRAF V600 Mutations in Oncogene Addicted NSCLC

Other Oncogenic Drivers

Table 5: Treatment Options for Other Oncogenic Drivers of NSCLC

References

Related to this Summary

UP NEXT

Find Us On

About

Membership

App

WebMD Network

Editions