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The impact of different first-line EGFR-TKIs on the clinical outcome of sequential osimertinib treatment in advanced NSCLC with secondary T790M.
Huang, YH, Tseng, JS, Hsu, KH, Chen, KC, Su, KY, Yu, SL, Chen, JJW, Yang, TY, Chang, GC
Scientific reports. 2021;(1):12084
Abstract
The impact of different first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)s to the clinical efficacy of osimertinib in EGFR-mutant non-small-cell lung cancer (NSCLC) patients with acquired T790M was still unclear. We enrolled 733 advanced EGFR-mutant NSCLC patients with gefitinib, erlotinib or afatinib as first-line EGFR-TKIs treatment for analysis. 373 patients received re-biopsies after progressive disease to first-line EGFR-TKIs treatment, and the total positive rate of T790M was 51.7%. 151 patients who harbored T790M received osimertinib as subsequent treatment. Among them, the median progression-free survival (PFS) of first-line EGFR-TKI (PFS1) was 14.0 months, and the median PFS of osimertinib (PFS2) was 10.1 months. The median PFS1 + PFS2 was 27.5 months, and the median overall survival from first-line EGFR-TKI was 61.3 months. Concerning different first-line EGFR-TKIs, the median PFS2 was 10.9 months in the gefitinib group, 10.0 months in the erlotinib group, and 6.7 months in the afatinib group (p = 0.534). The median PFS1 + PFS2 was 27.7 months, 26.8 months and 24.0 months in the gefitinib, erlotinib, and afatinib group, respectively (p = 0.575). In conclusion, both first-generation and second-generation EGFR-TKIs sequential osimertinib treatment provided good clinical efficacy in advanced EGFR-mutant NSCLC patients with acquired T790M mutation.
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Pimasertib-associated ophthalmological adverse events.
van Dijk, EHC, Kruit, WHJ, Jager, MJ, Luyten, GPM, Vingerling, JR, Boon, CJF
Acta ophthalmologica. 2018;(7):712-718
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Abstract
PURPOSE To analyse ophthalmological adverse events associated with mitogen-activated protein kinase kinase (MEK) inhibition with pimasertib treatment for metastatic cutaneous melanoma (CM). METHODS In this prospective observational, cohort-based, cross-sectional study, eight patients treated with the MEK inhibitor pimasertib received a complete ophthalmic examination. This included Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, visual field testing, colour vision testing, slit-lamp examination, applanation tonometry, indirect ophthalmoscopy, digital colour fundus photography and optical coherence tomography (OCT). In selected cases, fluorescein angiography was performed. RESULTS Serous subretinal fluid (SRF) developed in all patients, within a time frame of 9-27 days after the start of treatment. The fovea was involved in six of eight patients (75%). None of the patients with foveal SRF [excluding a patient who developed a bilateral retinal vein occlusion (RVO)] experienced visual symptoms. Subretinal fluid (SRF) decreased or resolved in all patients, despite continuation of study medication in six of eight patients (75%). Complaints in the CM patient (13%) consisted of experiencing a dark fleck in the inferior part of the visual field of the right eye 1 week after the start of treatment, due to an RVO. Subsequent intravitreal bevacizumab treatment resulted in functional and anatomical improvement. CONCLUSION Patients with metastatic CM who are treated with the MEK inhibitor pimasertib are at high risk of development of ocular adverse events including serous retinopathy and possibly RVO, stressing the need of adequate ophthalmological follow-up including OCT during administration of pimasertib, despite the fact that SRF generally does not lead to ophthalmological complaints.
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MEK inhibitor-associated retinopathy (MEKAR) in metastatic melanoma: Long-term ophthalmic effects.
Urner-Bloch, U, Urner, M, Jaberg-Bentele, N, Frauchiger, AL, Dummer, R, Goldinger, SM
European journal of cancer (Oxford, England : 1990). 2016;:130-8
Abstract
BACKGROUND Mitogen-activated protein kinase kinase (MEK) inhibitors have aroused considerable interest in oncology. Activity has been demonstrated in various types of cancer, especially melanoma. MEK inhibitors induce a transient retinopathy, considered to be a class effect. At present, only sparse data are available on retinal effects with long-term MEK inhibition. PATIENTS AND METHODS In this prospective, observational study, patients with advanced melanoma participating in different phase 1/2 or phase 3 clinical trials were treated with the MEK inhibitor binimetinib, with a v-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor, or with combination therapy. They underwent regular ophthalmological examinations including determination of visual function, biomicroscopy, dilated fundoscopy and optical coherence tomography (OCT) for a period of up to 2 years. Retinopathy was diagnosed on defined OCT criteria. RESULTS Sixty-two patients were investigated between 1st October 2011 and 31st July 2015: 13 were treated with the MEK inhibitor binimetinib alone, 10 with a selective BRAF inhibitor, and 39 with combination therapy. In 92% of patients on monotherapy and 100% of those on combination treatment, binimetinib caused dose-related lesions with serous neuroretinal detachments and oedema, strongly dependent on the time after medication. With continued treatment, retinal volume and thickness decreased to levels below baseline, without any apparent functional deficits or changes in structural integrity. CONCLUSIONS Binimetinib induces a specific retinopathy with daily fluctuations depending on the time interval after medication. The retinopathy partially recovers, but can still be detected many months later. Retinal thinning, possible first signs of retinal atrophy have been observed after long-term treatment, but, so far, without functional relevance.
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[DIETARY INTAKE AND NUTRITIONAL STATUS IN ONCOLOGY PATIENTS WHO START TREATMENT WITH TYROSINE KINASE INHIBITORS].
Higuera-Pulgar, I, Ribed, A, Carrascal-Fabian, ML, Bretón-Lesmes, I, Romero-Jiménez, RM, Cuerda-Compes, C, Velasco-Gimeno, C, Camblor-Álvarez, M, García-Peris, P
Nutricion hospitalaria. 2015;(3):1200-7
Abstract
BACKGROUND in recent years, researching about new oral antineoplastics has progressed while its impact on dietary intake and nutritional status (NS) hasn't developed enough yet. OBJECTIVES dietary intake and NS assessment in patients who start treatment with tyrosine kinase inhibitors (TKI) and evaluate its impact on them. METHODS an observational, prospective-six-months study, in which were included patients starting treatment with TKI. The intake was evaluated by a 24 h dietary record and a food frequency questionnaire. The NS was evaluated by anthropometric measurements and the patient-generated Global Subjective Assessment (PG-GSA); the results were compared with the Spanish references (SENC-semFYC, 2007 and O. Moreiras, 2013). Friedman test, χ2, Wilcoxon, Kruskal-Wallis and Mann-Whitney were used in the statistical analysis. Significance p < 0.05. RESULTS 22 patients (54.5% male) were included. At baseline, NS was adequate in 73.9% of patients according PG-GSA. Weight loss was no significant, although a high percentage of the energy and protein requirements hadn't been reached. The caloric intake was positively related with the number of meals. Dietary habits did not change during treatment. CONCLUSION dietary intake did not reach nutritional requirements at baseline. The TKI don't seem to affect the patient's intake and nutritional status. The research about these parameters before starting treatment could prevent future complications and it would guide the dietary advice.