374TiP LAURA: Osimertinib maintenance following definitive chemoradiation therapy (CRT) in patients (pts) with unresectable stage III epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC)

Lü, Shun; Casarini, Ignacio; Kato, Terufumi; Dols, M. Cobo; Özgüroǧlu, Mustafa; Gronde, Toon van der; Saggese, Matilde; Ramalingam, Suresh S.

doi:10.1016/j.annonc.2020.10.367

Cited by 3 publications

(2 citation statements)

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“…Despite limited data about EGFR TKI efficacy for patients with stage III EGFR -mutant NSCLC, evidence has suggested that these patients have inferior distant control following platinum-based CRT compared with those who have EGFR wild-type disease, especially central nervous system (CNS) control ( 32 ), highlighting the need for targeted therapy in patients with these disease features. The phase 3 LAURA clinical trial (NCT03521154) is currently enrolling unresectable EGFR -mutant stage III NSCLC patients to explore the efficacy and safety of osimertinib compared with placebo (2:1) until progression as maintenance therapy in patients without progression after concurrent or sequential chemoradiation ( 44 ). The primary end point is PFS per RECIST 1.1 according to blinded independent central review (BICR); and secondary end points include CNS PFS, PFS by mutational status, OS, safety, and tolerability ( Figure 1 ).…”

Section: Personalized Treatment In Locally-advanced Diseasementioning

confidence: 99%

Targeted therapies for unresectable stage III non-small cell lung cancer

Remón¹,

Hendriks²

2021

Mediastinum

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Until recently, the standard treatment in unresectable stage III non-small cell lung cancer was concurrent chemoradiotherapy, but often with dismal outcome. The introduction of consolidation treatment with immune checkpoint inhibitors has shifted the treatment landscape and prognosis of these patients. However, patients whose tumors harbors an epidermal growth factor receptor (EGFR) mutation derived less benefit, with an increased risk of immune-related adverse events. Moreover, current data suggested that patients with oncogenic addicted tumors, mainly EGFR -positive tumors, and also anaplastic lymphoma kinase ( ALK )-positive have poorer progression free survival after chemoradiotherapy. Indeed, these tumors have also inferior distant control compared with those who have wild-type disease, especially in the central nervous system, highlighting the need for assessing the role of targeted therapies in this patient population. It is speculated that outcome could probably increase with a consolidation treatment strategy including an EGFR tyrosine kinase inhibitor. However, a personalized treatment approach is not considered standard of care in this setting due to lack of robust evidence, as the majority of trials were performed in unselected patients, number of patients is limited and the majority of these studies were underpowered. In this review we summarize the role of tyrosine kinase inhibitors in unresectable stage III NSCLC, specifically focusing on EGFR -mutant tumors.

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Section: Personalized Treatment In Locally-advanced Diseasementioning

confidence: 99%

Targeted therapies for unresectable stage III non-small cell lung cancer

Remón¹,

Hendriks²

2021

Mediastinum

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“…Interestingly, 18%, 10%, and 10% of prescribers discussed self-funded oral tyrosine kinase inhibitor therapy in patients with EGFR, ALK, or ROS-1-mutated NSCLC, respectively, as a substitute for consolidation durvalumab. This is despite any current evidence to support consolidation tyrosine kinase inhibitor use in this setting with results from the LAURA study currently pending [12].…”

Section: Discussionmentioning

confidence: 92%

Variations in Patterns of Prescribing Durvalumab in Stage III Lung Cancer: A Survey of Australian Medical Oncologists

Nindra,

Bray,

Karikios

et al. 2024

Oncology

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Introduction: Local Australian guidelines for the optimal management of stage III unresectable non-small cell lung cancer (NSCLC) are lacking. The American Society of Clinical Oncology (ASCO) guidelines recommend consolidation durvalumab for all patients with unresectable stage III NSCLC, irrespective of their PD-L1 expression or driver mutation status. The European Society of Medical Oncology (ESMO) differs, with consolidation durvalumab only recommended in those patients whose tumours express PD-L1. Methods: Due to differing global guidelines, we conducted an Australia and New Zealand wide survey of medical oncologists specialising in thoracic cancer to determine the variations in patterns of prescribing durvalumab in stage III unresectable NSCLC. This survey was done electronically and sponsored by the Thoracic Oncology Group of Australia (TOGA). Results: Thirty-two medical oncologists completed the survey. In patients with EGFR-mutated stage III unresectable NSCLC, 6% of respondents stated that they prescribed durvalumab for all patients, while an additional 6% strongly recommended treatment. Forty-four percent suggested little benefit of consolidation durvalumab in this cohort, with an additional 19% advocating for observation only. In patients with PD-L1 negative (0%) stage III unresectable NSCLC, 13% of respondents prescribed durvalumab for all patients, while an additional 56% strongly recommended treatment. Interestingly, 18%, 10%, and 10% of prescribers discussed self-funded oral tyrosine kinase inhibitor therapy in patients with EGFR, ALK, or ROS-1-mutated NSCLC respectively as a substitute for consolidation durvalumab. Conclusion: Overall, the clinical practice of Australian and New Zealand Medical Oncologists is variable, but remains consistent with either the ASCO or ESMO guidelines. Local practice guidelines are required to ensure consistency in prescribing patterns across Australia, as well as providing evidence for self-funded treatments outside standard of care.

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Clinical, Pathologic, and Molecular Prognostic Factors in Patients with Early-Stage EGFR-Mutant NSCLC

Jung

Lim

Choi

et al. 2022

Clinical Cancer Research

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Purpose: In early-stage, Epidermal growth factor receptor mutation-positive (EGFR-M+) NSCLC, surgery remains the primary treatment, without personalized treatments. We aimed to identify risk factors for recurrence-free survival (RFS) to suggest personalized strategies. Patients and Methods: From January 2008 to August 2020, a total of 1,181 patients with pathological stage (pStage) IB–IIIA, non-squamous NSCLC. To identify clinicopathological risk factors, 1,181 patients with pStage IB–IIIA, common EGFR-M+ NSCLC were analyzed. Comprehensive genomic analysis was conducted in 56 matched case-control cases. Results: Among 1,181 patients, pStage IB, II, and IIIA comprised 48.9%, 28.0%, and 23.1% of subjects, respectively. Median RFS was 73.5 months, 48.7 months, and 22.7 months for each stage, respectively (P < 0.001). In multivariate analysis, pStage, micropapillary subtype, vascular invasion, pleural invasion, and pathological classification by cell of origin were associated with RFS. The non- terminal respiratory unit (non-TRU) of the RNA subtype (HR 3.49, 95%CI 1.72–7.09, P < 0.01) and TP53 mutation (HR 2.50, 95% CI 1.24–5.04, P = 0.01) were associated with poor RFS independent of pStage II or IIIA. After recurrence, patients with APOBEC mutation signature had inferior PFS of EGFR-TKI compared with that of patients without this signature (8.6 vs.·28.8 months, HR 4.16, 95%CI 1.28–13.46, P = 0.02). Conclusions: The low-risk group with TRU subtype and TP53 wild type without clinicopathological risk factors might not need adjuvant EGFR-TKIs. In the high-risk group with non-TRU subtype and/or TP 53 mutation, or clinicopathological risk factors, a novel adjuvant strategy including EGFR TKI and others needs to be investigated.

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374TiP LAURA: Osimertinib maintenance following definitive chemoradiation therapy (CRT) in patients (pts) with unresectable stage III epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC)

Cited by 3 publications

References 0 publications

Targeted therapies for unresectable stage III non-small cell lung cancer

Targeted therapies for unresectable stage III non-small cell lung cancer

Variations in Patterns of Prescribing Durvalumab in Stage III Lung Cancer: A Survey of Australian Medical Oncologists

Clinical, Pathologic, and Molecular Prognostic Factors in Patients with Early-Stage EGFR-Mutant NSCLC

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