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Canadian consensus: a new systemic treatment algorithm for advanced EGFR-mutated non-small-cell lung cancer.

ABSTRACT: Background:Multiple clinical trials for the treatment of advanced EGFR-mutated non-small-cell lung cancer (nsclc) have recently been reported. As a result, the treatment algorithm has changed, and many important clinical questions have been raised:? What is the optimal first-line treatment for patients with EGFR-mutated nsclc?? What is preferred first-line treatment for patients with brain metastasis?? What is the preferred second-line treatment for patients who received first-line first- or second-generation tyrosine kinase inhibitors (tkis)?? What is the preferred treatment after osimertinib?? What evidence do we have for treating patients whose tumours harbour uncommon EGFR mutations? Methods:A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on practice recommendations for the treatment of advanced EGFR-mutated nsclc. Results:The published overall survival results for osimertinib, combined with its central nervous system activity, have led to osimertinib becoming the preferred first-line treatment for patients with common EGFR mutations, including those with brain metastasis. Other agents could still have a role, especially when osimertinib is not available or not tolerated. Treatment in subsequent lines of therapy depends on the first-line therapy or on T790M mutation status. Treatment recommendations for patients whose tumours harbour uncommon EGFR mutations are guided mainly by retrospective and limited prospective evidence. Finally, the evidence for sequencing and combining tkis with chemotherapy, angiogenesis inhibitors, checkpoint inhibitors, and other new therapeutics is reviewed. Conclusions:This Canadian expert consensus statement and algorithm were driven by significant advances in the treatment of EGFR-mutated nsclc.

SUBMITTER: Melosky B

PROVIDER: S-EPMC7253730 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Canadian consensus: a new systemic treatment algorithm for advanced <i>EGFR-</i>mutated non-small-cell lung cancer.

Melosky B B Banerji S S Blais N N Chu Q Q Juergens R R Leighl N B NB Liu G G Cheema P P

Current oncology (Toronto, Ont.) 20200401 2

<h4>Background</h4>Multiple clinical trials for the treatment of advanced <i>EGFR-</i>mutated non-small-cell lung cancer (nsclc) have recently been reported. As a result, the treatment algorithm has changed, and many important clinical questions have been raised:■ What is the optimal first-line treatment for patients with <i>EGFR-</i>mutated nsclc?■ What is preferred first-line treatment for patients with brain metastasis?■ What is the preferred second-line treatment for patients who received fi ...[more]

PMID: 32489263

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Project description:BackgroundAlthough immune checkpoint inhibitors (ICIs) generally show poor therapeutic efficacy in patients with epidermal growth factor receptor (EGFR) mutations, certain research indicate that a small proportion of these patients do respond to ICIs. The present study sought to identify the features of patients with EGFR mutations who might benefit from ICIs from multiple studies and discussed the optimal treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations.MethodsThe profiles of 114 advanced NSCLC patients with EGFR mutations who received ICIs treatment were retrospectively reviewed. EGFR subtypes, programmed cell death ligand 1 (PD-L1) expression, and clinical characteristics regarding their impact on the efficacy of ICIs were investigated.ResultsPatients with major EGFR mutations (L858R or 19Del) had a shorter progression-free survival (PFS) and a lower objective response rate (ORR) as compared to patients with rare (20ins or G719X) and other EGFR mutations. Although not statistically significant, median overall survival (OS) tended to be longer in patients with negative (<1%) PD-L1 expression than with positive (≥1%) PD-L1 expression (15.61 vs. 7.40 months, p = 0.138). Median PFS and OS were significantly shorter in heavily treated patients (prior lines of therapy ≥3 lines vs. <3 lines: mPFS, 1.80 vs. 2.50 months, p = 0.003; mOS, 6.70 vs. 14.00 months, p = 0.031). ORR was also lower in patients who had received ≥3 prior lines of therapy compared to in those <3 prior lines of therapy (0.00% vs. 21.67%, p = 0.002).ConclusionPatients with major EGFR mutations showed poorer responses to ICIs than those with rare EGFR mutations. EGFR-mutated patients with lower PD-L1 expression showed a trend towards a longer OS after receiving ICIs. ICIs should be administered as early as possible to previously treated EGFR-mutated NSCLC patients. ICI-based combined therapies may be a direction for treatment of these patient subtypes in the future.

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Canadian consensus: a new systemic treatment algorithm for advanced EGFR-mutated non-small-cell lung cancer.

Publications

Canadian consensus: a new systemic treatment algorithm for advanced <i>EGFR-</i>mutated non-small-cell lung cancer.

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