Impact of Continuing First-Line EGFR Tyrosine Kinase Inhibitor Therapy Beyond RECIST Disease Progression in Patients with Advanced EGFR-Mutated Non-Small-Cell Lung Cancer (NSCLC): Retrospective GFPC 04-13 Study

Auliac, Jean Bernard; Fournier, Charles; Valette, C. Audigier; Pérol, Maurice; Bizieux, A.; Viñas, F.; Ho, Ching-Liang; Ouchlif, S. Bota; Corre, Romain; Garff, G. Le; Fournel, P.; Baize, Nathalie; Vergnenègre, A.; Arpin, D.; Marin, Benoît; Chouaïd, C.; Gervais, Radj

doi:10.1007/s11523-015-0387-4

Cited by 17 publications

(11 citation statements)

References 25 publications

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“…Median OS was similar for patients who received EGFR TKIs as post-PD therapy ( n = 36), which were mainly continuous erlotinib administration following RECIST PD ( n = 21) (Table 3), and for those who did not. In contrast to our findings, in a retrospective study of patients with activating EGFR mutations ( n = 123) who were treated with EGFR TKIs, OS showed a trend in favor of continuing versus discontinuing EGFR TKI treatment following RECIST PD (33.0 versus 21.2 months, respectively; p = 0.054) [25]. Furthermore, a retrospective clinical modeling study that evaluated the usefulness of EGFR TKI failure pattern for selecting subsequent management, suggested that the efficacy of EGFR TKI continuation differed between patients with gradual progression, local progression, and dramatic progression [26].…”

Section: Discussioncontrasting

confidence: 99%

Final overall survival in JO22903, a phase II, open-label study of first-line erlotinib for Japanese patients with EGFR mutation-positive non-small-cell lung cancer

et al. 2016

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BackgroundIn Japan, the clinical efficacy of erlotinib monotherapy in epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer was demonstrated in the phase II JO22903 trial, which reported a median progression-free survival of 11.8 months. Here we report final overall survival data from JO22903.MethodsJO22903 (JapicCTI-101085) was a single-arm, multicenter, phase II, open-label, non-randomized study of first-line erlotinib monotherapy in EGFR mutation-positive non-small-cell lung cancer. Eligible patients (≥20 years) with stage IIIB/IV or recurrent non-small-cell lung cancer and confirmed activating mutations of EGFR (exon 19 deletion or L858R point mutation in exon 21) received oral erlotinib 150 mg/day until disease progression or unacceptable toxicity. The primary endpoints were progression-free survival and safety; overall survival was a secondary endpoint.ResultsAt the final analysis, 102 patients were included in the modified intent-to-treat population and 103 in the safety population. Median follow-up was 32.3 months. Median overall survival was 36.3 months (95 % confidence interval 29.4–not reached). Subgroup analyses of overall survival suggested that the presence of brain metastases was a negative prognostic factor (median overall survival 22.7 months, 95 % confidence interval 19.6–29.4). The impact on overall survival of using versus not using EGFR tyrosine kinase inhibitors in any line of treatment following disease progression was unclear (median 32.8 versus 36.3 months, respectively). No new safety issues were observed.ConclusionIn this survival update, single-agent erlotinib achieved a median overall survival of more than 3 years in patients with EGFR mutation-positive non-small-cell lung cancer.

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Section: Discussioncontrasting

confidence: 99%

Final overall survival in JO22903, a phase II, open-label study of first-line erlotinib for Japanese patients with EGFR mutation-positive non-small-cell lung cancer

et al. 2016

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“…The IMPRESS study demonstrated no benefit of continued 1st EGFR-TKI with chemotherapy after RECIST progression in comparison to chemotherapy alone24. However, in patients with isolated disease progression after development of resistance to 1st EGFR-TKI, continuation of 1st EGFR-TKI in combination with local therapy is feasible, and subsequent treatment can be postponed252627. In our present study, patients with EGFR exon 19 deletion mutation who received long-term treatment with 1st or 2nd EGFR-TKI demonstrated a high prevalence of T790M mutation.…”

Section: Discussionmentioning

confidence: 99%

Association of EGFR Exon 19 Deletion and EGFR-TKI Treatment Duration with Frequency of T790M Mutation in EGFR-Mutant Lung Cancer Patients

Matsuo

Azuma

Sakai

et al. 2016

Sci Rep

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The most common event responsible for resistance to first- and second-generation (1st and 2nd) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is acquisition of T790M mutation. We examined whether T790M is related to clinicopathologic or prognostic factors in patients with relapse of EGFR mutant non-small cell lung cancer (NSCLC) after treatment with 1st or 2nd EGFR-TKIs. We retrospectively reviewed the T790M status and clinical characteristics of 73 patients with advanced or recurrent NSCLC who had been treated with EGFR-TKIs and undergone rebiopsy at Kurume University Hospital between March 2005 and December 2015. T790M mutation was more frequent in patients with EGFR exon 19 deletion mutation (63%, 26/41) than in those with L858R mutation (38%, 12/32) (p = 0.035). The median total duration of 1st or 2nd EGFR-TKI treatment was significantly longer in patients with T790M mutation than in those without (15.3 months vs 8.1 months, p < 0.001). Multivariate analysis revealed that the type of EGFR mutation and the total duration of EGFR-TKI treatment were significantly associated with T790M prevalence. Patients with EGFR exon 19 deletion mutation who receive long-term EGFR-TKI therapy show a high prevalence of T790M mutation. The present data are potentially important for clinical decision-making in NSCLC patients with EGFR mutation.

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“…In IMPRESS trial, continuation of gefitinib treatment after disease progression on gefitinib monotherapy did not prolong progression-free survival and overall survival in patients who received platinum-based doublet chemotherapy as subsequent line of treatment [26]. However, it is unclear that the efficacy of continuous using EGFR-TKIs without platinum doublets [27, 28]. Recently, we had been able to use third generation EGFR-TKIs that have great efficacy for NSCLC with EGFR T790M mutation in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Frequency of EGFR T790M mutation and multimutational profiles of rebiopsy samples from non-small cell lung cancer developing acquired resistance to EGFR tyrosine kinase inhibitors in Japanese patients

Kenmotsu

Serizawa

et al. 2016

BMC Cancer

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BackgroundThe majority of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Minimal information exists regarding genetic alterations in rebiopsy samples from Asian NSCLC patients who develop acquired resistance to EGFR-TKIs.MethodsWe retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who had undergone rebiopsies after developing acquired resistance to EGFR-TKIs. We analyzed 27 practicable samples using a tumor genotyping panel to assess 23 hot-spot sites of genetic alterations in nine genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2), gene copy number of EGFR, MET, PIK3CA, FGFR1, and FGFR2, and ALK, ROS1, and RET fusions. Additionally, 34 samples were analyzed by commercially available EGFR mutation tests.ResultsSixty-one patients underwent rebiopsy. Twenty-seven samples were analyzed using our tumor genotyping panel, and 34 samples were analyzed for EGFR mutations only by commercial clinical laboratories. Twenty-one patients (34 %) had EGFR T790M mutation. Using our tumor genotyping panel, MET gene copy number gain was observed in two of 27 (7 %) samples. Twenty patients received continuous treatment with EGFR-TKIs even after disease progression, and 11 of these patients had T790M mutation in rebiopsy samples. In contrast, only 10 of 41 patients who finished EGFR-TKI treatment at disease progression had T790M mutation. The frequency of T790M mutation in patients who received continuous treatment with EGFR-TKIs after disease progression was significantly higher than that in patients who finished EGFR-TKI treatment at disease progression (55 % versus 24 %, p = 0.018).ConclusionsThe frequency of T790M mutation in this study was lower than that in previous reports examining western patients. These results suggest that continuous treatment with EGFR-TKI after disease progression may enhance the frequency of EGFR T790M mutation in rebiopsy samples.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2902-0) contains supplementary material, which is available to authorized users.

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Impact of Continuing First-Line EGFR Tyrosine Kinase Inhibitor Therapy Beyond RECIST Disease Progression in Patients with Advanced EGFR-Mutated Non-Small-Cell Lung Cancer (NSCLC): Retrospective GFPC 04-13 Study

Abstract: NCT02293733.

Cited by 17 publications

References 25 publications

Final overall survival in JO22903, a phase II, open-label study of first-line erlotinib for Japanese patients with EGFR mutation-positive non-small-cell lung cancer

Final overall survival in JO22903, a phase II, open-label study of first-line erlotinib for Japanese patients with EGFR mutation-positive non-small-cell lung cancer

Association of EGFR Exon 19 Deletion and EGFR-TKI Treatment Duration with Frequency of T790M Mutation in EGFR-Mutant Lung Cancer Patients

Frequency of EGFR T790M mutation and multimutational profiles of rebiopsy samples from non-small cell lung cancer developing acquired resistance to EGFR tyrosine kinase inhibitors in Japanese patients

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