Osimertinib Maintenance After Definitive Chemoradiation in Patients With Unresectable EGFR Mutation Positive Stage III Non–small-cell Lung Cancer: LAURA Trial in Progress

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

doi:10.1016/j.cllc.2020.11.004

Cited by 55 publications

(36 citation statements)

References 19 publications

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“…Third-generation EGFR-TKI Osimertinib has been successfully shown to improve the survival of advanced and resectable early-stage EGFR-mutated NSCLC based on the results of pivotal clinical trials (e.g., the FLAURA and ADAURA trials) [ 34 , 35 ]. Osimertinib used as a consolidation therapy for post-CCRT unresectable stage III NSCLC with EGFR mutations currently under investigation in the LAURA trial [ 36 ], and the results of the LAURA trial may support using consolidation osimertinib in the future.…”

Section: Discussionmentioning

confidence: 99%

Durvalumab as Consolidation Therapy in Post-Concurrent Chemoradiation (CCRT) in Unresectable Stage III Non-Small Cell Lung Cancer Patients: A Multicenter Observational Study

Wang

Chiu

et al. 2021

Vaccines

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Background: The experience of using consolidation durvalumab in post-concurrent chemoradiation (CCRT) unresectable stage III non-small cell lung cancer (NSCLC) is rare in real-world clinical practice, and the factors associated with its efficacy are also unclear. We sought to analyze the efficacy of consolidation durvalumab and the factors associated with its efficacy using a multicenter observational study. Methods: The data for 61 patients with post-CCR unresectable stage III NSCLC receiving consolidation durvalumab at the Chang Gung Memorial Hospitals in Linkou, Keelung, Chiayi, and Kaohsiung from November 2017 to March 2020 were analyzed. (3) Results: The median post-CCRT progression-free survival (PFS) and time to metastatic disease or death (TMDD) for consolidation durvalumab were 14.0 months and 16.7 months, respectively. In multiple variant factors analysis, we found that an epidermal growth factor receptor (EGFR) mutation was an independently unfavorable predictive factor for consolidation durvalumab therapy regarding PFS. The median post-CCRT PFS was 6.50 months for EGFR-mutated patients and 33.63 months for EGFR wild-type and unknown patients (HR = 10.47; 95% CI, 4.55–24.07; p < 0.001). Conclusions: Consolidation durvalumab is effective and safe for post-CCRT unresectable stage III NSCLC in clinical practice, but EGFR mutation is an unfavorable factor for consolidation durvalumab. Thus, searching for a better consolidation therapy for EGFR-mutated patients is warranted.

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Section: Discussionmentioning

confidence: 99%

Durvalumab as Consolidation Therapy in Post-Concurrent Chemoradiation (CCRT) in Unresectable Stage III Non-Small Cell Lung Cancer Patients: A Multicenter Observational Study

Wang

Chiu

et al. 2021

Vaccines

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“…In this trial, neoadjuvant osimertinib as monotherapy or in combination with chemotherapy is compared to chemotherapy alone in patients with resectable EGFR-mutated NSCLC [ 52 ]. Another noteworthy, ongoing trial investigating osimertinib is the phase III, double-blind, randomized, placebo-controlled LAURA trial (NCT03521154), which aims to assess the efficacy and safety of osimertinib following CRT in patients with stage III unresectable EGFR-mutated NSCLC [ 53 ]. The results of these trials are highly anticipated as they will provide more insight on the role and timing of osimertinib in this heterogenous patient group.…”

Section: Discussionmentioning

confidence: 99%

Surgery after Induction Targeted Therapy and Immunotherapy for Lung Cancer

Allaeys

Berzenji

Schil

2021

Cancers

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Multimodality therapy for locally advanced non-small cell lung cancer (NSCLC) is a complex and controversial issue, especially regarding optimal treatment regimens for patients with ipsilateral positive mediastinal nodes (N2 disease). Many trials investigating neoadjuvant immunotherapy and targeted therapy in this subpopulation have shown promising results, although concerns have risen regarding surgical feasibility. A thorough literature review was performed, analyzing all recent studies regarding surgical morbidity and mortality. Despite the fact that two major trials investigating this subject were terminated early, the overall consensus is that surgical management seems feasible. However, dissection of hilar vessels may be challenging due to hilar fibrosis. Further research is necessary to identify the role of surgery in these multimodality treatment regimens, and to define matters such as the optimal treatment regimen, the dosage of the different agents used, the interval between induction therapy and surgery, and the role of adjuvant therapy.

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“…Although these phase II studies show encouraging results, they must be confirmed in phase III clinical trials. Currently, the phase III LAURA trial is underway, comparing osimertinib until progression vs placebo, as maintenance treatment after standard chemoradiotherapy[ 74 ].…”

Section: Egfr Tkis As Treatment For Unresectable Locally-advanced Diseasementioning

confidence: 99%

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer

Sotelo¹,

García²,

Torres-Mattos³

et al. 2021

WJCO

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Patients with early-stage non-small-cell lung cancer (NSCLC) are candidates for curative surgery; however, despite multiple advances in lung cancer management, recurrence rates remain high. Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival (OS), but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients. The high efficacy of tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor-mutated (EGFR) in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease. Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment, in patients with resected EGFR-mutated NSCLC, and shown that they significantly prolong disease-free survival (DFS), but this benefit does not translate to OS. Recently, an interim analysis of the ADAURA trial demonstrated that, surprisingly, osimertinib improved DFS. This led to the study being stopped early, leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup. These targeted agents are also being evaluated in locally-advanced disease, with promising results, although prospective studies with larger sample sizes are needed to confirm these results. In this article, we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.

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Osimertinib Maintenance After Definitive Chemoradiation in Patients With Unresectable EGFR Mutation Positive Stage III Non–small-cell Lung Cancer: LAURA Trial in Progress

Cited by 55 publications

References 19 publications

Durvalumab as Consolidation Therapy in Post-Concurrent Chemoradiation (CCRT) in Unresectable Stage III Non-Small Cell Lung Cancer Patients: A Multicenter Observational Study

Durvalumab as Consolidation Therapy in Post-Concurrent Chemoradiation (CCRT) in Unresectable Stage III Non-Small Cell Lung Cancer Patients: A Multicenter Observational Study

Surgery after Induction Targeted Therapy and Immunotherapy for Lung Cancer

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer

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