Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Beyond Progressive Disease: A Retrospective Analysis for Japanese Patients with Activating EGFR Mutations

Nishie, Kenichi; Kawaguchi, Tomoya; Tamiya, Akihiro; Mimori, Tomoyasu; Takeuchi, Naoko; Matsuda, Yoshinobu; Omachi, Naoki; Asami, Kazuhiro; Okishio, Kyoichi; Atagi, Shinji; Okuma, Tomohisa; Kubo, Akihito; Maruyama, Yoshihito; Kudoh, Shinzoh; Takada, Minoru

doi:10.1097/jto.0b013e31826913f7

Cited by 102 publications

(64 citation statements)

References 25 publications

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“…Most patients developed disease progression despite an initial response to TKIs. In recent years, continuing molecularly targeted therapy beyond RECIST-PD by physicians has increased in frequency [18,[21][22][23][24]. Moreover, several retrospective studies have suggested that molecularly targeted treatment beyond PD may be feasible and effective in patients with EGFR-positive mutations or ALK positive mutations [18,21,22].…”

Section: Discussionmentioning

confidence: 99%

Feasibility of continuing crizotinib therapy after RECIST-PD in advanced non-small cell lung cancer patients with ALK/ROS-1 mutations.

Cui

Jiang

2018

JCO

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Objectives: To study whether ongoing clinical benefits of continuing anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) inhibition are achieved by crizotinib treatment post progressive disease (PD) in advanced non-small cell lung cancer (NSCLC) patients harboring ALK/ROS1 mutations. Materials and methods: Demographic and clinicopathologic parameters were collected from 38 patients who continued crizotinib therapy beyond Response Evaluation Criteria in Solid Tumors (RECIST)-defined PD and analyzed. After adjusting for potential confounding factors, factors influencing the time from RECIST-PD to crizotinib discontinuation (progress-free survival 2, PFS2) were analyzed. Results: The median time from first dose treatment to RECIST-PD (PFS1) was 9.6 months (95% CI 5.6-13.6 months). The estimated median PFS2 was 5.9 months (95% CI 0.1-11.7 months). Six-and twelve-month crizotinib treatment probabilities after initial PD were 42.1% (95% CI 25.7-58.6%) and 21.1% (95% CI 7.5-34.6%), respectively. Patients who demonstrated RECIST-PD due to new lesions had a longer median PFS2 compared to patients who were attested to enlargement of original lesions (10.0 versus 2.4 months, p = 0.009). The median PFS2 was numerically longer among patients who received local therapy compared to those who did not receive local therapy, however the difference was not significant (9.9 versus 4.2 months, p = 0.094). Multivariable Cox regression analysis showed that only the progression pattern [new lesions versus enlargement of original lesions, HR = 0.329 (95% CI 0.138-0.782), p = 0.012] remained an independent prognostic factor of PFS2. Conclusion: Continuation of crizotinib therapy after RECIST-PD in Chinese NSCLC patients with positive ALK/ROS1 mutations is feasible in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Feasibility of continuing crizotinib therapy after RECIST-PD in advanced non-small cell lung cancer patients with ALK/ROS-1 mutations.

Cui

Jiang

2018

JCO

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“…Abrupt stopping of the TKI can results in a rapid disease flare resulting in severe deterioration, hospitalisation or death in up to one third of patients [72]. There are still few data concerning the best attitude to have in that situation but available reports suggest that continuing the TKI administration can result in a survival benefit [73,74]. However, the attitude must be adapted to the type of progression: patients relapsing on a single metastatic site may benefit from an aggressive treatment of the metastases (especially if these are localised in areas of poor drug penetration, for example the brain), asymptomatic patients with slow progression may continue TKI until symptomatic [75] while rapid progressing patients may be switched to chemotherapy.…”

Section: Egfr Tki In Egfr-mutated Patientsmentioning

confidence: 99%

Management of EGFR mutated nonsmall cell lung carcinoma patients

2015

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Number 8 in the series "Challenges and controversies in thoracic oncology" Edited by J-P. Sculier, B. Besse and P. Van Schil Correspondence:Anne-Pascale Meert, Institut Jules Bordet, 1 rue Héger-Bordet, 1000 Brussels, Belgium. E-mail: ap.meert@bordet.be ABSTRACT Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are common in the therapeutic armentarium of lung cancer today. Initially tested in an unselected population, they have been of limited usefulness until the identification EGFR gene mutations. Activating mutations generate conformational changes that result in a shift toward an active state of the catalytic domain and are associated with sensitivity to first generation EGFR TKI. Other mutations have been associated with resistance to these drugs, but for rare mutations there is limited data concerning their role in predicting response to EGFR TKI.To date, four molecules have been approved for the treatment of EGFR mutated lung cancer. Gefitinib and/or erlotinib are available in almost all countries. Afatinib has been approved by the US Food and Drug Administration and by the European Medicines Agency, and icotinib has been approved only in China. Other, more active, third generation agents with a higher binding affinity for the receptor, or that are directed against specific mutations, are under development. EGFR TKIs have a favourable impact on progression-free survival when given as first line treatment in mutated patients, but may also have a moderate effect as a salvage therapy and in maintenance in an unselected population.

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“…The Response Evaluation Criteria in Solid Tumors (RECIST) has been used as a standard method for assessing response and defining progression in cancer patients receiving treatment (15). However, there is more evidence every day, which suggests that continuing treatment beyond radiographic progression could confer an advantage, especially in patients treated with targeted therapy or immunotherapy (16). Treatment guidelines for NSCLC recommend continued use of TKI and local therapy after disease progression in asymptomatic patients.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of progression to tyrosine kinase inhibitors predict overall survival in patients with advanced non-small cell lung cancer harboring an EGFR mutation

Barrón

Cardona²,

Corrales³

et al. 2018

J. Thorac. Dis.

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Background: Non-small cell lung cancer (NSCLC) harboring EGFR-sensitizing mutations has a distinct biology and heterogeneous clinical behavior. We evaluated the characteristics to progression such as clinical patterns of progression (dramatic, gradual, and local) with the prognosis of NSCLC patients treated with tyrosine kinase inhibitors (TKIs). Methods: We reviewed 123 advanced-NSCLC patients with an EGFR-sensitizing mutation treated with TKIs (gefitinib, erlotinib and afatinib). We assessed patients according to clinical factors and progression pattern to TKIs at three centers. Results: For all patients, 58.5%, 31.7% and 9.8% harbored exon19 deletion, exon21 L858R mutation and other-sensitivity mutations, respectively. Median progression-free survival (PFS) was 8.8 months (95% CI: 7.9-9.7). Sixty percent of patients were asymptomatic. Dramatic-progression was the most frequent pattern (50.4%), followed by gradual-progression (32.5%), and local-progression (17.1%). Median overall survival (OS) was 23.1 months (95% CI: 17.4-28.9). In the univariate analysis, factors associated to a longer OS included pattern [gradual-progression (32.1), dramatic (19.5) and local (18.8 months), P=0.008], and the time to progression to TKI [>12 months (38.5), 6-12 months (19.1), <6 months (9.6), P<0.001]. Multivariate analysis showed that only time to progression to TKI was independently associated to OS and PFS. Conclusions: Factors at TKI progression associated to a longer OS can define a subset of patients who may benefit from continued TKI therapy, as well as from local-ablative therapy in progression sites, especially in patients without T790M or who lack access to third-generation TKI.

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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Beyond Progressive Disease: A Retrospective Analysis for Japanese Patients with Activating EGFR Mutations

Abstract: Continuous use of EGFR-TKI beyond PD may prolong overall survival compared with switching to cytotoxic chemotherapy in patients with activating EGFR mutations. A prospective study will be needed to confirm our results.

Cited by 102 publications

References 25 publications

Feasibility of continuing crizotinib therapy after RECIST-PD in advanced non-small cell lung cancer patients with ALK/ROS-1 mutations.

Feasibility of continuing crizotinib therapy after RECIST-PD in advanced non-small cell lung cancer patients with ALK/ROS-1 mutations.

Management of EGFR mutated nonsmall cell lung carcinoma patients

Characteristics of progression to tyrosine kinase inhibitors predict overall survival in patients with advanced non-small cell lung cancer harboring an EGFR mutation

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