Updated overall survival (OS) from extended follow up in ARCHER 1050: A randomized phase III study comparing dacomitinib with gefitinib as first-line therapy for patients (pts) with EGFR mutations

Mok, Tony; Cheng, Ying; Zhou, Xiangdong; Lee, K.H.; Nakagawa, Kazuhiko; Niho, Seiji; Linke, R.; Rosell, Rafael; Corral, J.; Migliorino, Maria Rita; Płużański, Adam; Noonan, Kay; Tang, Yiyun; Wilner, Keith D.; Wu, Yi‐Long

doi:10.1093/annonc/mdz446.018

Cited by 15 publications

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“…This finding was similar to the LUX‐Lung 7 study finding of a higher difference in the response rates to afatinib and gefitinib in patients harboring L858R substitutions 10 . Another similar result was the ARCHER 1050 study finding that the OS benefit of dacomitinib was more significant in patients harboring L858R substitutions 25 . Taken together, these findings indicate that the irreversible EGFR‐TKIs might provide greater survival benefits among patients harboring L858R substitutions.…”

Section: Discussionsupporting

confidence: 80%

First‐line treatment with irreversible tyrosine kinase inhibitors associated with longer OS in EGFR mutation‐positive non‐small cell lung cancer

Chen

et al. 2020

Thoracic Cancer

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Background Few studies have compared the efficacy of the irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI), afatinib, with that of reversible EGFR‐TKIs. Therefore, this study assessed the effectiveness of afatinib, erlotinib, and gefitinib in terms of OS (overall survival) and progression‐free survival (PFS) in EGFR mutation‐positive advanced non‐small cell lung cancer (NSCLC) patients. Methods Patients with EGFR mutation‐positive advanced NSCLC who sought treatment from December 2013 to June 2018, at a tertiary referral center were retrospectively analyzed. These patients were treated with afatinib or a reversible EGFR‐TKI (erlotinib or gefitinib) until disease progression, intolerable adverse events, or death. The Kaplan‐Meier and log‐rank tests were then used to compare the OS and PFS of the patients. We further analyzed the survival differences among the subgroup of patients without brain metastases. Results Of the 363 patients enrolled, 134 and 229 received first‐line afatinib and first‐line reversible EGFR‐TKI, respectively. Those given afatinib had better OS (39.3 vs. 26.0 months; HR 0.65, P = 0.033) and PFS (14.1 vs.11.2 months; HR 0.58, P < 0.001). Of the 246 patients without brain metastases, 93 and 153 received first‐line afatinib and a first‐line reversible EGFR‐TKI, respectively. Those given afatinib had a better OS (52.6 vs. 24.9 months; HR 0.62, P = 0.0030) and PFS (17.7 vs. 11.1 months; HR 0.51, P < 0.001). The survival benefit was more significant in the subgroup of patients with L858R substitutions. Conclusions The results indicated that afatnib resulted in significantly better OS and PFS than gefitnib and erlotinib for EGFR mutation‐positive advanced NSCLC patients without brain metastases. Key points Significant findings of the study Afatnib resulted in significantly better overall survival and progression‐free survival than gefitnib and erlotinib for EGFR mutation‐positive advanced non‐small cell lung cancer patients without brain metastases. What this study adds This study helps fill the gap in our limited understanding of the differences in the efficacy of the irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI), afatinib, with that of reversible EGFR‐TKIs.

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Section: Discussionsupporting

confidence: 80%

First‐line treatment with irreversible tyrosine kinase inhibitors associated with longer OS in EGFR mutation‐positive non‐small cell lung cancer

Chen

et al. 2020

Thoracic Cancer

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“…Moreover, as noted earlier, the NMA used in this study [29,30] differs from other previously published NMAs of EGFR TKIs [44,45,46,47,48] because it included more recently published data for OS (e.g. mature OS data for osimertinib from FLAURA [26] and updated OS data for dacomitinib from ARCHER 1050 [27]), employed more stringent selection criteria regarding data specific to EGFRm patients. However, the results of the NMA used in this study are directionally consistent with previously published NMAs for indirect comparisons of PFS, while the differences in indirect comparisons of OS are due to previously published NMAs [46,48]…”

Section: Discussionmentioning

confidence: 99%

“…The base-case time horizon used in the analysis was 15 years, i.e. a lifetime perspective for this patient population (based on the typical OS from published trials [26,27]). This time horizon was chosen to capture all relevant clinical and economic outcomes that occur within the patient cohort in the economic model.…”

Section: Model Structure and Settingsmentioning

confidence: 99%

“…[29,30] To extrapolate the PFS and OS curves over the time horizon, first Kaplan-Meier curves for PFS and OS were generated using the patient-level data for the gefitinib arm from the ARCHER 1050 study. [27,31] Table 1 and Supplementary Figure 1 Force on Indirect Treatment Comparison recommendations. [35] In the NMA, the relative efficacy of dacomitinib and other first-line EGFR TKI therapies was assessed in terms of OS and PFS.…”

Section: Accepted Manuscript Data Sources -Clinicalmentioning

confidence: 99%

“…The NMA used in this study focused only on EGFR TKI monotherapies, included more recently published data (e.g. mature OS data for osimertinib from FLAURA [26] and updated OS data for dacomitinib from ARCHER 1050 [27]), and employed more stringent selection criteria regarding data specific to EGFRm patients (namely it was restricted to randomized studies in which patients were molecularly selected for EGFRm positive status and did not include non-randomized, post-hoc EGFRm positive subgroup analyses).…”

Section: Accepted Manuscript Data Sources -Clinicalmentioning

confidence: 99%

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The cost-effectiveness of dacomitinib in first-line treatment of advanced/metastatic epidermal growth factor receptor mutation-positive non-small-cell lung cancer (EGFRm NSCLC) in Sweden

Nilsson

Gál²,

Houisse³

et al. 2021

Journal of Medical Economics

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Aims: Although the benefit of first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) over chemotherapy in EGFR mutation-positive (EGFRm) non-smallcell lung cancer (NSCLC) has been demonstrated in clinical trials, the optimal treatment sequence remains unclear. The objective of our study was to evaluate the cost-effectiveness of dacomitinib in Sweden versus afatinib and osimertinib in first-line treatment of EGFRm NSCLC. Materials and methods: A partitioned survival model was developed with three health states: progression-free, post-progression, and death. Progression-free and overall survival curves were used to inform movements between states. Clinical data were taken from randomized trials, compared via a network meta-analysis (NMA). Utility data were taken from published studies and costs from national Swedish sources. The model used a 15-year time horizon and a Swedish healthcare payer perspective. Sensitivity and scenario analyses were performed. Results: The base-case analysis showed that dacomitinib accrued a total of 2.10 qualityadjusted life years (QALYs) at a total cost of Swedish krona (SEK) 874,615. The incremental cost-effectiveness ratio (ICER) for dacomitinib versus afatinib was SEK 461,556 per QALY gained. The ICER of osimertinib versus dacomitinib, where the small QALY gains of the former came at a high additional cost, was SEK 11,444,709. Deterministic and probabilistic sensitivity analyses confirmed robustness of these results; changes to drug and medical resource use costs and overall survival had the greatest impact on ICER estimates. Limitations: This model is subject to uncertainty associated with extrapolating long-term A c c e p t e d M a n u s c r i p t treatment effects from shorter trial follow-up periods, although this would also be a limitation when using direct comparison or time-dependent hazard ratios. The NMA was limited by the use of indirect comparison although sensitivity analyses supported the robustness of our findings. Conclusions: Our model demonstrated dacomitinib is cost-effective for first-line EGFRm NSCLC treatment in Sweden versus afatinib and osimertinib.

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Targeted therapy in lung cancer: Are we closing the gap in years of life lost?

et al. 2022

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Purpose Patients with non‐small cell lung cancer (NSCLC) that harbor driver mutations are associated with a cancer diagnosis at a younger age. While targeted therapies provide deep remissions and durable benefit in a subset of patients, it is unclear whether targeted therapies bridge the gap in years of life lost (YLL) in these younger NSCLC patients with targetable mutations in comparison to generally older NSCLC patients without actionable driver mutations. Materials and Methods Retrospective cross‐sectional study using landmark trials leading to the approval of targeted therapies in NSCLC with actionable mutations. We evaluated all targeted therapies as well as chemotherapy and IO regimens for the treatment of NSCLC through FDA Oncology Announcements and NCCN Guidelines for NSCLC (version 4.2021). Results We estimated the YLL for each driver mutation, cumulative median duration of response (DOR) with targeted therapies by mutation type, and percentage of estimated improvement in YLL from NSCLC targeted therapies. The median ages at diagnosis (in years) for patients whose tumors express targetable mutations were: 47.6 (NTRK); 52.0 (ALK); 62.0 (HER2); 57.0 (ROS1); 61.4 (RET); 63.0 (BRAF); 69.0 (EGFR); and 72.0 (MET). For comparison, the median age at diagnosis for patients without driver mutations, regardless of PD‐L1 status was 71 years. The median DOR (in years) for patients whose tumors express the same mutations include: 0.9 (NTRK); 3.9 (ALK); 0.6 (HER2); 6.2 (ROS1); 2.2 (RET); 1.5 (BRAF); 3.1 (EGFR); and 2.4 (MET). The median DOR for patients without driver mutations was 1.2 years. The cumulative estimated survival time (years; median age at diagnosis plus the median DOR or OS) for patients whose tumors express targetable mutations were: 48.5 (NTRK); 55.9 (ALK); 62.6 (HER2); 63.2 (ROS1); 63.6 (RET); 64.5 (BRAF); 72.1 (EGFR); and 74.4 (MET). The cumulative estimated survival time for patients without driver mutations, regardless of PD‐L1 status, was 72.2 years of age. We calculated the number of years NSCLC is diagnosed earlier in patients with targetable mutations as follows: 23.4 (NTRK), 19 (ALK), 14 (ROS1), 11 (EGFR), 9.6 (RET), 9 (HER2), and 8 (BRAF). The percent difference (%) ameliorated in YLL by mutation type is as follows: 44.3 (ROS1), 28.2 (EGFR), 22.9 (RET), 20.5 (ALK), 18.8 (BRAF), 6.4 (HER2), and 3.7 (NTRK). Conclusion Although targeted therapies have paved the way for significant progress toward providing a survival benefit to many young patients with advanced NSCLC with actionable mutations, it is evident that these therapies still leave a wide gap in the YLL in these younger patients compared to generally older individuals with advanced NSCLC without targetable mutations.

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Updated overall survival (OS) from extended follow up in ARCHER 1050: A randomized phase III study comparing dacomitinib with gefitinib as first-line therapy for patients (pts) with EGFR mutations

Cited by 15 publications

References 0 publications

First‐line treatment with irreversible tyrosine kinase inhibitors associated with longer OS in EGFR mutation‐positive non‐small cell lung cancer

First‐line treatment with irreversible tyrosine kinase inhibitors associated with longer OS in EGFR mutation‐positive non‐small cell lung cancer

The cost-effectiveness of dacomitinib in first-line treatment of advanced/metastatic epidermal growth factor receptor mutation-positive non-small-cell lung cancer (EGFRm NSCLC) in Sweden

Targeted therapy in lung cancer: Are we closing the gap in years of life lost?

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