Canadian Perspectives: Update on Inhibition of ALK-Positive Tumours in Advanced Non-Small-Cell Lung Cancer

Melosky, Barbara; Cheema, Parneet K.; Agulnik, J.; Albadine, Roula; Bebb, D. Gwyn; Blais, Normand; Burkes, Ronald L.; Butts, Charles; Card, Paul B.; Chan, Alicia; Hirsh, Vera; Ionescu, Diana N.; Juergens, Rosalyn A.; Morzycki, W.; Poonja, Zia; Sangha, Randeep; Tehfé, Mustapha; Tsao, Ming‐Sound; Vincent, Mark; Xu, Zhaolin; Liu, G.

doi:10.3747/co.25.4379

Cited by 14 publications

(16 citation statements)

References 65 publications

(107 reference statements)

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“…In our study, the initial ALK inhibitor was likely a first-generation ALK inhibitor given the time frame of the study. Treatment guidelines currently recommend the use of multiple ALK inhibitors [ 21 , 24 ]. Our findings support sequencing through ALK therapies before proceeding to chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Observational Study of ALK-Inhibitor Therapy Sequencing and Outcomes in Patients with ALK-Positive Non-small Cell Lung Cancer

Waterhouse

Espirito

Chioda

et al. 2020

Drugs - Real World Outcomes

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Background Data are sparse concerning the sequential use of multiple anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Objective This study investigated sequencing and outcomes among patients receiving multiple ALK inhibitors. Patients and Methods This was a retrospective observational cohort study of adult patients with ALK-positive NSCLC treated with available first- and second-generation ALK inhibitors from 1 September 2011 to 31 December 2017. Duration of therapy (DOT) and overall survival (OS) were assessed with the Kaplan–Meier method. A multivariable linear regression analysis was performed to assess if DOT with a preceding ALK inhibitor was predictive of DOT for subsequent ALK inhibitor treatments. Results A total of 410 patients were analyzed: 57% received 1 ALK inhibitor; 35%, 2 ALK inhibitors; and 8%, 3–4 ALK inhibitors. Among those receiving > 1 ALK inhibitor ( n = 177), 60% received a crizotinib-led sequence and 39% an alectinib-led sequence. Nearly 60% of the overall population received chemotherapy prior to their first ALK inhibitor. Median OS for the study population was 28 months, 15 months in patients who received 1 ALK inhibitor, 42 months in patients who received 2 ALK inhibitors, and 56 months in patients who received 3–4 ALK inhibitors. Longer DOT of the first ALK inhibitor was associated with increased DOT of the second ( p < 0.0001), and longer DOT of the second ALK inhibitor was associated with increased DOT of the third ( p < 0.0001). Conclusions This study provides initial information on real-world treatment patterns following the introduction of new ALK inhibitors, and supports the use of sequential ALK therapies.

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Section: Discussionmentioning

confidence: 99%

Retrospective Observational Study of ALK-Inhibitor Therapy Sequencing and Outcomes in Patients with ALK-Positive Non-small Cell Lung Cancer

Waterhouse

Espirito

Chioda

et al. 2020

Drugs - Real World Outcomes

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“…The WBRT-30-SCLC needs to be validated in a separate cohort of patients in the future because advances in systemic therapies, especially the development immuno-therapies that can cross the blood-brain-barrier will have an impact on the survival of patients with brain metastases from lung cancer. Promising results were reported for immune checkpoint inhibitors or alk inhibitors in patients with brain metastases from non-small cell lung cancer [23,24,25,26]. Moreover, a phase 2 study of maintenance pembrolizumab in 45 patients with extensive disease SCLC, of whom 22% had treated brain metastases, suggested that a subset of these patients could benefit from this treatment [27].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Diagnosis-Specific Survival Scores for Patients with Small-Cell Lung Cancer Irradiated for Brain Metastases

Rades

Hansen

Schild

2019

Cancers

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Diagnosis-specific survival scores including a new score developed in 157 patients with brain metastases from small-cell lung cancer (SCLC) receiving whole-brain radiotherapy (WBRT) with 30 Gy in 10 fractions (WBRT-30-SCLC) were compared. Three prognostic groups were designed based on the 6-month survival probabilities of significant or almost significant factors, (age, performance score, number of brain metastases, extra-cerebral metastasis). Six-month survival rates were 6% (6–11 points), 44% (12–14 points) and 86% (16–19 points). The WBRT-30-SCLC was compared to three disease-specific scores for brain metastasis from SCLC, the original and updated diagnosis-specific graded prognostic assessment DS-GPA classifications and the Rades-SCLC. Positive predictive values (PPVs) used to correctly predict death ≤6 months were 94% (WBRT-30-SCLC), 88% (original DS-GPA), 88% (updated DS-GPA) and 100% (Rades-SCLC). PPVs to predict survival ≥6 months were 86%, 75%, 76% and 100%. For WBRT-30-SCLC and Rades-SCLC, differences between poor and intermediate prognoses groups and between intermediate and favorable prognoses groups were significant. For both DS-GPA classifications, only the difference between poor and intermediate prognoses groups was significant. Of these disease-specific tools, Rades-SCLC appeared to be the most accurate in identifying patients dying ≤6 months and patients surviving ≥6 months after irradiation, followed by the new WBRT-30-SCLC and the DS-GPA classifications.

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“…Therefore, the model can produce estimates that approximate recent reports of ALK patient survival, but base-case estimates may be more indicative of general aNSCLC patient survival as opposed to survival of patients at academic centers or in clinical trials. As new effective treatment approaches [42] are more broadly adopted, iTEN estimates of survival are likely to increase.…”

Section: Discussionmentioning

confidence: 99%

Development, validation and results from the impact of treatment evolution in non-small cell lung cancer (iTEN) model

Moldaver¹,

Hurry

Evans

et al. 2020

Lung Cancer

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Treatment of advanced NSCLC (aNSCLC) is rapidly evolving, as new targeted and immuno-oncology (I-O) treatments become available. The iTEN model was developed to predict the cost and survival benefits of changing aNSCLC treatment patterns from a Canadian healthcare system perspective. This report describes iTEN model development and validation. Materials & methods: A discrete event patient simulation of aNSCLC was developed. A modified Delphi process using Canadian clinical experts informed the development of treatment sequences that included commonly used, Health Canada approved treatments of aNSCLC. Treatment efficacy and the timing of progression and death were estimated from published Kaplan-Meier progression free and overall survival data. Costs (2018 CDN$) included were: drug acquisition and administration, imaging, monitoring, adverse events, physician visits, best supportive care, and end-of-life. Results and conclusion: Clinical validity of the iTEN model was assessed by comparing model survival predictions to published real-world evidence (RWE). Four RWE studies that reported the overall survival of patients treated with a broad sampling of common aNSCLC treatment patterns were used for validation. The validation coefficient of determination was R 2 = 0.95, with the model generally producing estimates that were neither optimistic nor conservative. The model estimated that current Canadian practice patterns yield a median survival of almost 13 months, a five-year survival rate of 3% and a lifetime per-treated-patient cost of $110,806. Cost and survival estimates are presented and were found to vary by aNSCLC subtype. In conclusion, the iTEN model is a reliable tool for forecasting the impact on cost and survival of new treatments for aNSCLC. [1]. It is the leading cause of cancer-related mortality in Canada, accounting for approximately 26% of all cancer-related deaths [1]. Nonsmall cell lung cancer (NSCLC) is the most common form, representing approximately 80-85% of all lung cancers [2]. Approximately 50% of

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Canadian Perspectives: Update on Inhibition of ALK-Positive Tumours in Advanced Non-Small-Cell Lung Cancer

Cited by 14 publications

References 65 publications

Retrospective Observational Study of ALK-Inhibitor Therapy Sequencing and Outcomes in Patients with ALK-Positive Non-small Cell Lung Cancer

Retrospective Observational Study of ALK-Inhibitor Therapy Sequencing and Outcomes in Patients with ALK-Positive Non-small Cell Lung Cancer

Comparison of Diagnosis-Specific Survival Scores for Patients with Small-Cell Lung Cancer Irradiated for Brain Metastases

Development, validation and results from the impact of treatment evolution in non-small cell lung cancer (iTEN) model

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