Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study

Novello, Silvia; Mazières, Julien; Oh, I-J.; Castro, Javier de; Migliorino, Maria Rita; Helland, Åslaug; Dziadziuszko, Rafał; Griesinger, Frank; Kotb, Ahmed; Zeaiter, Ali; Cardona, Andrés F.; Balas, Bogdana; Johannsdottir, Hrefna Kristin; Das-Gupta, A.; Wolf, Jürgen

doi:10.1093/annonc/mdy121

Cited by 264 publications

(226 citation statements)

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“…Some clinical trials have demonstrated that there is good efficacy of second generation ALK‐TKI in comparison to chemotherapy for crizotinib‐pretreated ALK‐positive NSCLC patients . In addition, some studies showed the remarkable efficacy of next generation ALK‐TKI tailored to the secondary mutation .…”

Section: Discussionmentioning

confidence: 99%

“…The superiority of crizotinib, a first generation ALK‐tyrosine kinase inhibitor (ALK‐TKI), to standard chemotherapy has been demonstrated in patients with ALK‐positive advanced NSCLC previously treated with platinum‐based chemotherapy . Sequentially, next generation ALK‐TKIs, such as alectinib, ceritinib, brigatinib and lorlatinib, have shown remarkable clinical efficacy in ALK‐positive NSCLC . However, even if patients initially respond well to ALK‐TKI, the majority eventually experience disease progression due to various mechanisms, including secondary mutations within the ALK tyrosine kinase domain and activation of alternative signaling pathways …”

Section: Introductionmentioning

confidence: 99%

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Short progression‐free survival of ALK inhibitors sensitive to secondary mutations in ALK‐positive NSCLC patients

et al. 2019

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Background Most non‐small cell lung cancer (NSCLC) patients relapse on anaplastic lymphoma kinase‐tyrosine kinase inhibitor (ALK‐TKI) therapy because of acquired resistance. Rebiopsy is recommended to provide optimal therapy after relapse for some ALK‐TKI therapies; however, little clinical data exists on the clinical efficacy of ALK‐TKI tailored to secondary mutation. Methods A retrospective study was conducted to analyze the patterns of ALK‐TKI treatment and clinical outcomes, including progression free survival (PFS), of ALK‐positive NSCLC patients who received rebiopsy. Based on the rebiopsy results, secondary mutations in the ALK gene that were shown to be associated with the efficacy of ALK‐TKI therapy in the preclinical or clinical setting were defined as “sensitive mutations (SM)”. Results Among 71 patients who received ALK‐TKI for NSCLC at our institution, 20 patients received rebiopsy, and secondary SM were found in eight patients. The objective response rate (ORR) of the cases with SM who received ALK‐TKI therapy was 88.9%, while the ORR of the patients without SM who received ALK TKI or chemotherapy was 20.0%; however, the PFS of the patients with SM was relatively short (with SM vs. without SM: 5.6 months vs. 5.1 months). Conclusions The selection of ALK‐TKI based on the rebiopsy result was associated with a high ORR and relatively short PFS. The mechanism responsible for the short PFS of sensitive ALK‐TKI to secondary mutation should be clarified.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Short progression‐free survival of ALK inhibitors sensitive to secondary mutations in ALK‐positive NSCLC patients

et al. 2019

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“…According to the updated results, the median PFS for alectinib in first-line treatment was 34.8 months which was almost three times longer than the standard first-line treatment for ALK rearrangement [89]. Besides, the phase III ALUR study directly compared alectinib with chemotherapy in crizotinib-pretreated ALK-positive non-small cell lung cancer [111]. Median PFS was 9.6 months with alectinib and 1.4 months with chemotherapy as second-line treatment indicating an absolute clinical role of alectinib as a first-line setting.…”

Section: Alectinibmentioning

confidence: 99%

Emerging therapies for non-small cell lung cancer

et al. 2019

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Recent advances in the field of novel anticancer agents prolong patients' survival and show a promising future. Tyrosine kinase inhibitors and immunotherapy for lung cancer are the two major areas undergoing rapid development. Although increasing novel anticancer agents were innovated, how to translate and optimize these novel agents into clinical practice remains to be explored. Besides, toxicities and availability of these drugs in specific regions should also be considered during clinical determination. Herein, we summarize emerging agents including tyrosine kinase inhibitors, checkpoint inhibitors, and other potential immunotherapy such as chimeric antigen receptor T cell for non-small cell lung cancer attempting to provide insights and perspectives of the future in anticancer treatment.

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“…The mean duration of second-line treatment was set at 50.1 weeks, irrespective of the nature of the treatment. This value corresponds to the mean values of the duration of PFS reported in clinical trials evaluating the use of alectinib [16], crizotinib [17] and ceritinib [17]. Third-line treatment was considered to be followed from the end of second-line treatment until the patient died (or until the end of the ten-year modelling period).…”

Section: Model Inputsmentioning

confidence: 99%

Cost-effectiveness of alectinib compared to crizotinib for the treatment of first-line ALK+ advanced non-small-cell lung cancer in France

Marine¹,

Monnier²,

Téhard

et al. 2020

PLoS ONE

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The aim of the study is to evaluate the cost-effectiveness of alectinib for first-line treatment of ALK+ advanced non-small-cell lung cancer compared to crizotinib in the French setting. This study used a partitioned survival model, with three discrete health states (progressionfree survival, post-progression survival and death). Survival probabilities were derived from a randomised Phase III clinical trial comparing alectinib to crizotinib (ALEX). Beyond the length of the trial (18 months), the efficacy of both treatments was considered equivalent. Occurrence of adverse events or brain metastases were considered as inter-current events. Utilities (and disutilities for intercurrent adverse events) derived from the EQ-5D were applied. Costs were attributed using standard French national public health tariffs. Projected mean overall survival was 4.62 years for alectinib and 4.18 years for crizotinib. Projected mean progression-free survival was 30.30 months for alectinib and 16.13 months for crizotinib. The total number of quality-adjusted life years projected was 3.40 for alectinib and 2.84 for crizotinib. The projected total cost of treatment over the lifetime of the model was € 246,022 for alectinib and € 195,486 for crizotinib. This extra cost was principally attributable to treatment acquisition costs and management before progression. Alectinib was associated with lower costs related to brain metastases and to management post-progression. The incremental cost per life year gained was 115,334 €/year and the incremental costeffectiveness ratio was 90,232 €/QALY. First-line treatment of ALK+ NSCLC with alectinib provides superior clinical outcomes to crizotinib and is cost-effective in the French context. OPEN ACCESS Citation: Sivignon M, Monnier R, Tehard B, Roze S (2020) Cost-effectiveness of alectinib compared to crizotinib for the treatment of first-line ALK+ advanced non-small-cell lung cancer in France. PLoS ONE 15(1): e0226196. https://doi.org/ 10.patients who develop cancers bearing these fingerprints [3]. In particular, inhibitors of the epidermal growth factor receptor (EGFR), such as gefitinib and erlotinib, or anaplastic lymphoma kinase (ALK), such as crizotinib and alectinib, have been developed. Mutations in the Erb-1 gene encoding EGFR are present in 10-20% of patients developing squamous cell lung cancer and rearrangements of the ALK gene are present in around 3.2% of patients developing nonsmall cell lung cancer (NSCLC) [3,4].Crizotinib, the first ALK inhibitor to be introduced for the treatment of lung cancer in 2011, has rapidly become the gold standard for this type of cancer [5,6]. However, its longterm effectiveness is compromised by the development of resistance and progression of central nervous system (CNS) disease [7]. Alectinib is an orally-administered inhibitor of ALK which has been demonstrated to be effective in the treatment of ALK+ NSCLC [8]. Since this molecule is lipophilic and is not a substrate for p-glycoprotein, it penetrates the CNS effectively and can prevent the growth o...

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Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study

Cited by 264 publications

References 13 publications

Short progression‐free survival of ALK inhibitors sensitive to secondary mutations in ALK‐positive NSCLC patients

Short progression‐free survival of ALK inhibitors sensitive to secondary mutations in ALK‐positive NSCLC patients

Emerging therapies for non-small cell lung cancer

Cost-effectiveness of alectinib compared to crizotinib for the treatment of first-line ALK+ advanced non-small-cell lung cancer in France

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