Survival Outcomes in EGFR Mutation-Positive Lung Cancer Patients Treated with Gefitinib until or beyond Progression

Moiseyenko, Fedor V.; Moiseyenko, Vladimir; Aleksakhina, Svetlana N.; Chubenko, Vyacheslav A.; Volkov, Nikita; Kozyreva, K.S. Kozyreva (); Kramchaninov, Michail M.; Zhuravlev, A.S. Zhuravlev (); Shelekhova, Ksenya V.; Ivantsov, Alexandr O.; Venina, Aigul R.; Preobrazhenskaya, Elena V.; Mitiushkina, Natalia V.; Iyevleva, Aglaya G.; Imyanitov, Evgeny N.

doi:10.1159/000449024

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…This result supports the clinical findings that treating with gefitinib post-progression may still provide patients with a benefit [26]. …”

Section: Discussionsupporting

confidence: 88%

“…Our results also indicate that, although no further shrinkage is gained from continuing on gefitinib, post 8 weeks, the re-growth rate of the resistant clone appears to be slower than that observed for doublet chemotherapy. This result supports the clinical findings that treating with gefitinib post-progression may still provide patients with a benefit [26].…”

Section: Discussionsupporting

confidence: 88%

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Resistance models to EGFR inhibition and chemotherapy in non-small cell lung cancer via analysis of tumour size dynamics

Mistry

Helmlinger

Al‐Huniti

et al. 2019

Cancer Chemother Pharmacol

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Purpose Imaging time-series data routinely collected in clinical trials are predominantly explored for covariates as covariates for survival analysis to support decision-making in oncology drug development. The key objective of this study was to assess if insights regarding two relapse resistance modes, de-novo (treatment selects out a pre-existing resistant clone) or acquired (resistant clone develops during treatment), could be inferred from such data. Methods Individual lesion size time-series data were collected from ten Phase III study arms where patients were treated with either first-generation EGFR inhibitors (erlotinib or gefitinib) or chemotherapy (paclitaxel/carboplatin combination or docetaxel). The data for each arm of each study were analysed via a competing models framework to determine which of the two mathematical models of resistance, de-novo or acquired, best-described the data. Results Within the first-line setting (treatment naive patients), we found that the de-novo model best-described the gefitinib data, whereas, for paclitaxel/carboplatin, the acquired model was preferred. In patients pre-treated with paclitaxel/carboplatin, the acquired model was again preferred for docetaxel (chemotherapy), but for patients receiving gefitinib or erlotinib, both the acquired and de-novo models described the tumour size dynamics equally well. Furthermore, in all studies where a single model was preferred, we found a degree of correlation in the dynamics of lesions within a patient, suggesting that there is a degree of homogeneity in pharmacological response. Conclusions This analysis highlights that tumour size dynamics differ between different treatments and across lines of treatment. The analysis further suggests that these differences could be a manifestation of differing resistance mechanisms. Electronic supplementary material The online version of this article (10.1007/s00280-019-03840-3) contains supplementary material, which is available to authorized users.

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“…This result supports the clinical findings that treating with gefitinib post-progression may still provide patients with a benefit [26]. …”

Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 88%

Resistance models to EGFR inhibition and chemotherapy in non-small cell lung cancer via analysis of tumour size dynamics

Mistry

Helmlinger

Al‐Huniti

et al. 2019

Cancer Chemother Pharmacol

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“…Specifically, epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and L858R point mutation, are well recognized as driver mutations and promising predictors of the efficacy of EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib, erlotinib, and afatinib, in NSCLC patients harboring EGFR mutations [3][4][5][6][7]. In addition, EGFR-TKIs are recommended for elderly people [8][9][10] and they are effective regardless of the treatment timing in patients with NSCLC harboring EGFR mutations [11,12]. Recently, a large cohort study reported that gefitinib therapy resulted in a 5-year survival rate of approximately 20% in NSCLC patients harboring…”

Section: Introductionmentioning

confidence: 99%

Impact of EGFR-Tyrosine Kinase Inhibitors on Postoperative Recurrent Non-Small-Cell Lung Cancer Harboring EGFR Mutations

et al. 2017

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Background: It is unclear whether there is a difference in the efficacy of treatment by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) between patients with postoperative recurrent non-small-cell lung cancer (NSCLC) and those with stage IV NSCLC harboring EGFR mutations. Patients and Methods: The records of NSCLC patients harboring EGFR mutations who were treated with gefitinib or erlotinib were retrospectively reviewed, and the treatment outcomes were evaluated. Moreover, we performed an immunohistochemical analysis of PD-L1 expression in tumor lesions of the postoperative recurrence group. Results: In 205 patients, both the progression-free survival (PFS) time (9.4 vs. 16.9 months) and the median survival time (24.7 vs. 37.4 months) were significantly longer in the postoperative group than in the stage IV group. Additionally, multivariate analysis identified that postoperative recurrence was an independent predictor of PFS and overall survival, as were performance status and smoking status. The PFS durations were 15.7 and 16.6 months for the high- and low-PD-L1 expression groups, respectively, and no significant difference was observed (P = 0.73). Conclusions: The findings of this study provide a valuable rationale for considering postoperative recurrence as a predictive factor for favorable PFS and overall survival in patients with NSCLC harboring activating EGFR mutations who receive EGFR-TKIs.

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“…Most studies enrolled patients within the past 20 years and all studies were published within the past 10 years. There were 13 studies which evaluated ppPFS (1,758 patients) ( 17 – 20 , 23 – 27 , 30 , 31 , 36 , 37 ), 20 studies which evaluated ppOS (8,271 patients) ( 13 , 15 – 17 , 19 , 21 , 23 , 24 , 27 , 28 , 30 , 32 – 37 , 39 , 41 , 44 ), and 12 studies evaluated OS from initiation of drugs (1,579 patients) ( 14 , 15 , 18 , 22 , 25 , 32 , 34 , 38 , 40 – 43 ). The drugs provided to the TBP groups fell into four categories: 14 studies used EGFR TKIs (43.8%) ( 13 , 14 , 17 – 19 , 22 , 23 , 25 , 26 , 29 , 30 , 32 , 36 , 44 ), 4 employed ALK TKIs (12.5%) ( 15 , 16 , 34 , 35 ), 10 studies used immunotherapy (31.3%) ( 28 , 31 , 33 , 37 – 43 ), and 4 articles used anti-angiogenesis (12.4%) ( 20 , 21 , 24 , 27 ).…”

Section: Resultsmentioning

confidence: 99%

Treatment beyond progression in non-small cell lung cancer: A systematic review and meta-analysis

2022

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ObjectivesTreatment beyond progression (TBP) is defined as treatment continuing in spite of disease progression, according to the Response Evaluation Criteria In Solid Tumors. We performed a systematic review and meta-analysis to provide evidence for the effects of TBP on lung cancer survival.Materials and methodsThis study has been conducted following the PRISMA guidelines. A systematic review of PubMed, MEDLINE, Embase, and Cochrane Collaboration Central Register of Controlled Clinical Trials from the inception of each database to December 2021 was conducted. Two authors independently reviewed articles for inclusion and extract data from all the retrieved articles. Random-effects meta-analysis was performed using Comprehensive Meta-Analysis software, version 3 (Biostat, Englewood, NJ, USA). Hazard ratios (HRs) with the corresponding 95% confidence intervals (CI) were used for survival outcomes.ResultsWe identified five (15.6%) prospective randomized trials and twenty-seven (84.4%) retrospective observational studies of a total of 9,631 patients for the meta-analysis. 3,941 patients (40.9%) were in a TBP group and 5,690 patients (59.1%) were in a non-TBP group. There is a statistically significant advantage for patients who received TBP compared with those who did not in post progression progression-free survival (ppPFS), post progression overall survival (ppOS), and overall survival (OS) from initiation of drugs (ppPFS: HR, 0.746; 95% CI, 0.644-0.865; P<0.001; ppOS: HR, 0.689; 95% CI, 0.596-0.797; P<0.001; OS from initiation of drugs: HR, 0.515; 95% CI, 0.387-0.685; P<0.001)ConclusionThis study provides further evidence in support of TBP for NSCLC, however, these results require cautious interpretation. Large, randomized, controlled trials investigating the efficacy of TBP in lung cancer treatment are warranted.Systemic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/ identifier CRD42021285147

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Survival Outcomes in EGFR Mutation-Positive Lung Cancer Patients Treated with Gefitinib until or beyond Progression

Cited by 6 publications

References 28 publications

Resistance models to EGFR inhibition and chemotherapy in non-small cell lung cancer via analysis of tumour size dynamics

Resistance models to EGFR inhibition and chemotherapy in non-small cell lung cancer via analysis of tumour size dynamics

Impact of EGFR-Tyrosine Kinase Inhibitors on Postoperative Recurrent Non-Small-Cell Lung Cancer Harboring EGFR Mutations

Treatment beyond progression in non-small cell lung cancer: A systematic review and meta-analysis

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