Comparison Between Second- and Third-generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors as First-line Treatment in Patients With Non-small-cell Lung Cancer: A Retrospective Analysis

Mitsuya, Sho; Tsuruoka, Kenjiro; Kanaoka, Kiyoe; Funamoto, Tomoya; Tsuji, Hiroyuki; Matsunaga, Ninso; Nakamura, Takahiko; Tamura, Yasuaki; Imanishi, Masafumi; Ikeda, Soichiro; Fujisaka, Yasuhito; Goto, Isao; Imagawa, Akihisa

doi:10.21873/anticanres.15331

Cited by 8 publications

(4 citation statements)

References 22 publications

(23 reference statements)

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“…The GioTag study is a global observational study for evaluating survival rates among patients with EGFR mutationpositive NSCLC treated with sequential afatinib and osimertinib therapy (25), which reported a median OS duration NSCLC: Non-small cell lung cancer; PFS: progression-free survival. (22,(27)(28)(29). By contrast, patients with T790M mutation undergoing chemotherapy without 3G EGFR-TKIs experienced similar OS as those without T790M mutation, which was worse than the OS of patients with T790M undergoing osimertinib treatment (Figure 3B and Figure 4).…”

Section: Figure 2 T790m Positivity According To Egfr Mutation (A) And...mentioning

confidence: 91%

Real-world Afatinib Outcomes in Advanced Non–small Cell Lung Cancer Harboring EGFR Mutations

Chen

Chang

et al. 2022

Anticancer Res

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Background/Aim: Afatinib is a standard treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Osimertinib can overcome the treatment resistance-associated EGFR T790M mutation, and the sequence of afatinib followed by osimertinib is an effective therapeutic strategy for NSCLC patients. This study comprehensively evaluated the outcomes of sequential therapy following frontline afatinib and identified predictive factors for T790M mutation acquisition. Patients and Methods: Data from patients with advanced NSCLC treated with frontline afatinib at a Taiwanese hospital group from June 2014 to March 2018 were retrospectively reviewed. The EGFR T790M mutation was detected by tissue sequencing or liquid biopsy. The patients' clinicopathological features were collected, and univariate and multivariate analyses were performed to identify potential predictive and prognostic factors. Results: A total of 635 patients treated with afatinib were enrolled in this study. Until August 2021, 553 patients experienced progression, and 225 patients underwent T790M mutation testing. The T790M positive rate was 54.2%. Both exon 19 deletion and progressionfree survival were associated with T790M positivity. Osimertinib was found to be effective in T790M-positive but not T790Mnegative NSCLC. The median overall survival (OS) was 61.8 months for patients with T790M mutation undergoing later-line osimertinib compared with 30.1 months for patients without T790M mutation undergoing chemotherapy only. Osimertinib independently prolonged OS after afatinib progression. Conclusion: This study confirmed the efficacy of sequential afatinib and osimertinib treatment. T790M mutation detection and osimertinib availability are important for prolonging survival in patients with NSCLC harboring EGFR mutations.

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Section: Figure 2 T790m Positivity According To Egfr Mutation (A) And...mentioning

confidence: 91%

Real-world Afatinib Outcomes in Advanced Non–small Cell Lung Cancer Harboring EGFR Mutations

Chen

Chang

et al. 2022

Anticancer Res

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“…The outcomes after thoracic irradiation for lung cancer can be improved with precision radiotherapy and novel systemic agents (4,(18)(19)(20)(21)(22)(23). Another modern approach to improve the outcomes after loco-regional radiotherapy for lung cancer is the use of personalized treatment programs.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Factors of Survival After Radiotherapy for Lung Cancer–The Impact of Smoking Pack Years

Werner¹,

Glatzel²,

Bohnet³

et al. 2022

In Vivo

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Background/Aim: The prognostic role of smoking pack years after thoracic irradiation for lung cancer needs further clarification, since previous studies showed conflicting results. Therefore, this study investigated potential prognostic factors for survival including pack years in 170 lung cancer patients receiving local radiotherapy. Patients and Methods: Twelve factors were retrospectively evaluated for survival including age, sex, tumor site, histology, primary tumor stage, nodal stage, distant metastasis, radiation dose, upfront surgery or systemic treatment, pulmonary function, and number of pack years. Results: On univariate analyses, absence of distant metastasis (p=0.049), radiation dose >56 Gy (p=0.019), and ≤40 pack years (p=0.005) were significantly associated with better survival. In the multivariate analysis, number of pack years (hazard ratio 2.18, 95% confidence interval 1. 25-3.82, p=0.006) maintained significance; distant metastasis (p=0.34) and radiation dose (p=0.16) were not significant. Conclusion: Number of pack years was an independent predictor of survival after thoracic irradiation for lung cancer.Lung cancer is one of the most threatening malignant diseases with the highest number of disease-associated deaths worldwide (1). Many lung cancer patients with locoregionally advanced disease receive thoracic irradiation with or without systemic therapies (2). During the last decade, modern precision radiotherapy techniques such as intensitymodulated radiotherapy and volumetric modulated arc therapy have become available in many countries (3, 4). For curative treatment of lung cancer, several dose-fractionation regimens with different overall treatment times are available (4, 5). When selecting the appropriate individual dosefractionation regimen, the patient's personal situation, age, comorbidity and also the survival prognosis should be considered. In case of non-small cell lung cancer (NSCLC), patients with favorable prognoses are, depending on age, performance status and comorbidity index, often candidates for conventionally fractionated radiotherapy (5×2.0 Gy per week) with total doses of 60-70 Gy (4, 5). Patients with less favorable prognoses or other limitations may receive hypofractionated (doses per fraction >2.0 Gy) irradiation, e.g. with 2.75 Gy per fraction up to 55 Gy (5). For curative treatment of small-cell lung cancer (SCLC), commonly used dose-fractionation regimens include hyper-fractionated radiotherapy with 45 Gy in 30 fractions (2×1.5 Gy per day) and conventionally fractionated radiotherapy with total doses of 60-66 Gy (4, 6, 7). Like patients with NSCLC, those with SCLC and poor survival prognoses or significant other limitations may also receive hypo-fractionated radiotherapy.These considerations suggest that it is important to know a patient's survival prognosis as precisely as possible to provide the best individual treatment. Several prognostic factors for survival have already been identified for lung cancer patients receiving thoracic irradiation (8, 9). However, c...

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“…12 In another recent real-world study in Japan, sequential afatinib and osimertinib conferred median OS of over 5 years, albeit on a small dataset. 13 Together, these findings suggest that sequential afatinib and osimertinib could be a particularly promising regimen in Asian patients with EGFR mutation-positive NSCLC.…”

Section: Introductionmentioning

confidence: 88%

Sequential Afatinib and Osimertinib in Asian Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer and Acquired T790M: Combined Analysis of Two Global Non-Interventional Studies

Miura¹,

Jung²,

Lee³

et al. 2022

OTT

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Two recent non-interventional trials, GioTag and UpSwinG, demonstrated encouraging time-to-treatment failure (TTF) and overall survival (OS) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) (Del19 or L858R) who received sequential afatinib/osimertinib, especially in Asians. Here, we have undertaken a combined analysis of Asian patients from both studies. Materials and Methods: Existing medical/electronic records were identified for consecutive EGFR-tyrosine kinase inhibitor (TKI)-naïve patients who received first-line afatinib/second-line osimertinib in "real-world" practice (all T790M-positive). Patients with active brain metastases were excluded. The primary objective was TTF. OS was a key secondary objective. Results: One hundred and sixty-eight patients were analyzed. Most patients were recruited from South Korea or Japan (52/21%). At the start of afatinib, median age (range) was 61.5 years (35-88), 58% were female, Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0/1/≥2) was 29/62/9%, 17% had brain metastases, and EGFR mutation status (Del19/L858R) was 65/35%. At the start of osimertinib, ECOG PS (0/1/≥2) was 22/61/17% and 14% had brain metastases. Median TTF and OS were 30.0 months (95% CI: 24.5-32.5) and 45.2 months (95% CI: 41.7-71.1), respectively. Median OS was 63.5 months in patients with a Del19 mutation. Median OS in patients with brain metastases or ECOG PS ≥2 was 26.4 and 33.1 months, respectively. Conclusion: Sequential afatinib/osimertinib showed encouraging activity in Asian patients with EGFR mutation-positive NSCLC and T790M-mediated acquired resistance, especially those with Del19-positive disease. Activity was observed across "real-world" patients including those with poor ECOG PS and/or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib.

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Comparison Between Second- and Third-generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors as First-line Treatment in Patients With Non-small-cell Lung Cancer: A Retrospective Analysis

Cited by 8 publications

References 22 publications

Real-world Afatinib Outcomes in Advanced Non–small Cell Lung Cancer Harboring EGFR Mutations

Real-world Afatinib Outcomes in Advanced Non–small Cell Lung Cancer Harboring EGFR Mutations

Prognostic Factors of Survival After Radiotherapy for Lung Cancer–The Impact of Smoking Pack Years

Sequential Afatinib and Osimertinib in Asian Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer and Acquired T790M: Combined Analysis of Two Global Non-Interventional Studies

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