A retrospective study of alectinib versus ceritinib in patients with advanced non–small-cell lung cancer of anaplastic lymphoma kinase fusion in whom crizotinib treatment failed

Kuo, Chih-Hsi S.; Tung, Pi-Hung; Huang, Allen Chung-Cheng; Wang, Chin‐Chou; Chang, John Wen‐Cheng; Liu, Chien-Ying; Chung, Fu‐Tsai; Fang, Yueh‐Fu; Guo, Yike; Yang, Cheng‐Ta

doi:10.1186/s12885-021-08005-1

Cited by 5 publications

(9 citation statements)

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“…Assessment of Alectinib vs Ceritinib in ALK-Positive NSCLC in Phase 2 Trials and Real-world Data estimates. However, given that comparisons of trial data vs RWD and RWD vs RWD produced consistent findings and that findings of a beneficial effect of alectinib from this study appear to be consistent with a retrospective analysis of progression-free survival and objective response in a cohort of patients in Taiwan for the same indication, 24 overall conclusions from this study are expected to be robust. Besides OS, there may be other patient-important measures of effectiveness (eg, toxicity) that were not examined in this study.…”

Section: Jama Network Open | Oncologysupporting

confidence: 76%

“…Besides OS, there may be other patient-important measures of effectiveness (eg, toxicity) that were not examined in this study. However, prior retrospective analyses suggest that alectinib may be associated with fewer adverse events than ceritinib . Note that unbiased estimation of treatment effects using weighting depends on correct specification of the propensity model.…”

Section: Discussionmentioning

confidence: 99%

“…However, prior retrospective analyses suggest that alectinib may be associated with fewer adverse events than ceritinib. 24 Note that unbiased estimation of treatment effects using weighting depends on correct specification of the propensity model. Although a doubly robust estimator was used to reduce dependence on this assumption, it is not guaranteed to provide unbiased estimates if both the propensity and outcome models were misspecified.…”

Section: Jama Network Open | Oncologymentioning

confidence: 99%

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Assessment of Alectinib vs Ceritinib in ALK-Positive Non–Small Cell Lung Cancer in Phase 2 Trials and in Real-world Data

et al. 2021

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IMPORTANCE Quantitative assessment of bias from unmeasured confounding and missing data can help evaluate uncertainty in findings from indirect comparisons using real-world data (RWD).OBJECTIVE To compare the effectiveness of alectinib vs ceritinib in terms of overall survival (OS) in patients with ALK-positive, crizotinib-refractory, non-small cell lung cancer (NSCLC) and to assess the sensitivity of these findings to unmeasured confounding and missing data assumptions. DESIGN, SETTING, AND PARTICIPANTSThis comparative effectiveness research study compared patients from 2 phase 2 alectinib trials and real-world patients. Patients were monitored from June 2013 to March 2020. Comparisons of interest were between alectinib trial data vs ceritinib RWD and alectinib RWD vs ceritinib RWD. RWD treatment groups were selected from nationally representative cancer data from US cancer clinics, the majority from community centers. Participants were ALK-positive patients aged 18 years or older with advanced NSCLC, prior exposure to crizotinib, and Eastern Cooperative Oncology Group Performance Status (PS) of 0 to 2. Data analysis was performed from October 2020 to March 2021. EXPOSURES Initiation of alectinib or ceritinib therapy. MAIN OUTCOMES AND MEASURESThe main outcome was OS. RESULTSIn total, there were 355 patients: 183 (85 men [46.4%]) in the alectinib trial, 91 (43 men [47.3%]) in the ceritinib RWD group, and 81 (38 men [46.9%]) in the alectinib RWD group. Patients in the alectinib trial were younger (mean [SD] age, 52.53 [11.18] vs 57.97 [11.71] years), more heavily pretreated (mean [SD] number of prior therapy lines, 1.95 [0.72] vs 1.47 [0.81]), and had more favorable baseline ECOG PS (ECOG PS of 0 or 1, 165 patients [90.2%] vs 37 patients [77.1%]) than those in the ceritinib RWD group. The alectinib RWD group (mean [SD] age, 58.69 [11.26] years) had more patients with favorable ECOG PS (ECOG PS of 0 or 1, 49 patients [92.4%] vs 37 patients [77.1%])and more White patients (56 patients [72.7%] vs 53 patients [62.4%]) compared with the ceritinib group. Compared with ceritinib RWD, alectinib-exposed patients had significantly longer OS in alectinib trials (adjusted hazard ratio [HR], 0.59; 95% CI, 0.44-0.75; P < .001) and alectinib RWD (HR, 0.46; 95% CI, 0.29-0.63; P < .001) after adjustment for baseline confounders. For the worst-case HR estimate of 0.59, residual confounding by a hypothetical confounder associated with mortality and treatment by a risk ratio greater than 2.24 was required to reverse the findings. Conclusions were robust to plausible deviations from random missingness for missing ECOG PS and underrecorded comorbidities and central nervous system metastases in RWD. CONCLUSIONS AND RELEVANCEAlectinib exposure was associated with longer OS compared with ceritinib in patients with ALK-positive NSCLC, and only substantial levels of bias examined reversed (continued)

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Section: Jama Network Open | Oncologysupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Jama Network Open | Oncologymentioning

confidence: 99%

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Assessment of Alectinib vs Ceritinib in ALK-Positive Non–Small Cell Lung Cancer in Phase 2 Trials and in Real-world Data

et al. 2021

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“… 14 The high CNS protection activity of alectinib was also reported in a retrospective analysis in select patients with advanced ALK -positive NSCLC failing crizotinib treatment; patients receiving alectinib experienced a lower incidence of CNS progression than those receiving ceritinib (cause-specific HR 0.10, 95% CI 0.01-0.78). 15 …”

Section: Discussionmentioning

confidence: 99%

Final overall survival analysis from the phase III J-ALEX study of alectinib versus crizotinib in ALK inhibitor-naïve Japanese patients with ALK-positive non-small-cell lung cancer

et al. 2022

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“…Therefore, rebiopsy to discover the resistant mutations might be considered to determine the optimal treatment for ALK-inhibitor-resistant NSCLC [79]. In retrospective studies of ALK-positive advanced NSCLC, ceritinib demonstrated a longer median PFS compared to crizotinib for first-line treatment [80], and a second-generation ALK inhibitor, alectinib demonstrated a lower incidence of CNS progression and a tendency toward superior PFS compared to ceretinib in specific patients who had progressed on crizotinib [81].…”

Section: Alkmentioning

confidence: 99%

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

Luo

Liang²,

Huang³

et al. 2022

IJMS

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Lung cancers are life-threatening malignancies that cause great healthcare burdens in Taiwan and worldwide. The 5-year survival rate for Taiwanese patients with lung cancer is approximately 29%, an unsatisfactorily low number that remains to be improved. We first reviewed the molecular epidemiology derived from a deep proteogenomic resource in Taiwan. The nuclear factor erythroid 2-related factor 2 (NRF2)antioxidant mechanism was discovered to mediate the oncogenesis and tumor progression of lung adenocarcinoma. Additionally, DNA replication, glycolysis and stress response are positively associated with tumor stages, while cell-to-cell communication, signaling, integrin, G protein coupled receptors, ion channels and adaptive immunity are negatively associated with tumor stages. Three patient subgroups were discovered based on the clustering analysis of protein abundance in tumors. The first subgroup is associated with more advanced cancer stages and visceral pleural invasion, as well as higher mutation burdens. The second subgroup is associated with EGFR L858R mutations. The third subgroup is associated with PI3K/AKT pathways and cell cycles. Both EGFR and PI3K/AKT signaling pathways have been shown to induce NRF2 activation and tumor cell proliferation. We also reviewed the clinical evidence of patient outcomes in Taiwan given various approved targeted therapies, such as EGFR-tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK)inhibitors, in accordance with the patients’ characteristics. Somatic mutations occurred in EGFR, KRAS, HER2 and BRAF genes, and these mutations have been detected in 55.7%, 5.2%, 2.0% and 0.7% patients, respectively. The EGFR mutation is the most prevalent targetable mutation in Taiwan. EML4-ALK translocations have been found in 9.8% of patients with wild-type EGFR. The molecular profiling of advanced NSCLC is critical to optimal therapeutic decision-making. The patient characteristics, such as mutation profiles, protein expression profiles, drug-resistance profiles, molecular oncogenic mechanisms and patient subgroup systems together offer new strategies for personalized treatments and patient care.

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A retrospective study of alectinib versus ceritinib in patients with advanced non–small-cell lung cancer of anaplastic lymphoma kinase fusion in whom crizotinib treatment failed

Cited by 5 publications

References 32 publications

Assessment of Alectinib vs Ceritinib in ALK-Positive Non–Small Cell Lung Cancer in Phase 2 Trials and in Real-world Data

Assessment of Alectinib vs Ceritinib in ALK-Positive Non–Small Cell Lung Cancer in Phase 2 Trials and in Real-world Data

Final overall survival analysis from the phase III J-ALEX study of alectinib versus crizotinib in ALK inhibitor-naïve Japanese patients with ALK-positive non-small-cell lung cancer

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

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