本帖最后由 荷花池荒岛 于 2014-4-25 08:00 编辑
http://www.medscape.com/viewarticle/820728_3
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If afatinib hasn't supplanted erlotinib as first-line treatment for patients with an activating EGFR mutation in the United States, we might question whether it is an obvious choice for EGFR mutation-positive patients with acquired resistance to a reversible EGFR TKI. Unfortunately, current data remain inconclusive on this question. In the LUX-Lung 1 trial, 585 patients who had responded or demonstrated stable disease for at least 12 weeks on either gefitinib or erlotinib were randomly assigned (2:1) to receive either afatinib or placebo.[6] The response rate in the afatinib group was only 7%, and despite an improvement of median PFS from 1.1 to 3.3 months, there was no significant improvement in median overall survival. Efficacy of the combination of afatinib and cetuximab for EGFR mutation-positive patients with acquired resistance has been far more provocative, as evidenced in albeit a small phase 1/2 study.[7] Although promising, the combination of afatinib and cetuximab requires further study in a large multicenter randomized trial to clarify whether it should emerge as a leading option for EGFR mutation-positive patients with acquired resistance.
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http://mct.aacrjournals.org/content/12/5/589.short
An irreversible ErbB family blocker is expected to inhibit tumors with activating epidermal growth factor receptor (EGFR) mutations more strongly than reversible EGFR tyrosine kinase inhibitors and to overcome acquired resistance to the T790M secondary mutation. Eleven-week-old transgenic mice with Egfr exon 19 deletion mutation were treated with afatinib, gefitinib, or vehicle for 4 weeks. All mice were sacrificed at 15 weeks of age, and the number of superficial left lung tumors with a long axis exceeding 1 mm was counted. The afatinib-treated group had significantly fewer tumors than the vehicle group (P < 0.01) and tended to have fewer tumors than the gefitinib-treated group (P = 0.06). Pathologically, gefitinib-treated mice had clearer, more nodular tumors than afatinib-treated mice. Immunoblotting showed that afatinib suppressed not only pEGFR but also pHER2, and induced apoptosis for longer periods than gefitinib. Subsequently, when each drug was administered 5 days per week until death, afatinib significantly enhanced mouse survival compared with gefitinib (median survival time: 456 days vs. 376.5 days; log-rank test, P < 0.01). Finally, the combination of afatinib with bevacizumab was found to be superior to either drug alone in exon 19 deletion/T790M and L858R/T790M xenograft tumors. Overall, afatinib was more potent than gefitinib in tumors harboring an exon 19 deletion mutation, and the combination of afatinib with bevacizumab efficiently suppressed tumors harboring the T790M secondary mutation. Mol Cancer Ther; 12(5); 589–97. ©2013 AACR.
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http://www.medwirenews.com/46/10 ... esistant_NSCLC.html
medwireNews: Afatinib is effective when given to patients with non-small-cell lung cancer (NSCLC) who have progressed during treatment with erlotinib and/or gefitinib, phase II trial results reveal.
Although response rates were modest, the data support the potential value of afatinib in patients with advanced epidermal growth factor receptor (EGFR)-mutant tumors who have developed resistance to EGFR tyrosine kinase inhibitor therapy.
The trial included 62 patients with stage IIIB/IV pulmonary adenocarcinoma, of whom 45 (72.6%) tested positive for EGFR mutations. All patients had received at least 12 weeks’ treatment with erlotinib and/or gefitinib in the third- or fourth-line setting; 51 (82.3%) patients were considered to have acquired resistance to these therapies.
All patients were started on afatinib, an oral irreversible ErbB family blocker, at a dose of 50 mg/day until progressive disease or intolerable toxicity; the mean duration of treatment was 4.59 months.
Of 61 evaluable patients, five (8.2%) achieved a partial response and 35 (57.4%) had stable disease for at least 6 weeks, giving a disease control rate of 65.6%.
Most responses occurred within 8 weeks of starting afatinib and the mean duration of response was 24.4 weeks, note Nobuyuki Katakami (Kobe City Medical Center General Hospital, Japan) and colleagues, writing in the Journal of Clinical Oncology.
Afatinib reduced the size of target lesions in 79% of patients, with nine (16%) patients having at least a 30% reduction in tumor size. Median progression-free survival was 4.4 months and median overall survival was 19.0 months.
Subgroup analysis found that the treatment benefit was consistent irrespective of patient gender, type of prior therapy, number of previous chemotherapy regimens, and mutation type.
The most common toxicities were diarrhea, rash/acne, and stomatitis, with frequencies of 100%, 91.9%, and 85.5%, respectively. Around two thirds of patients required a reduction in their afatinib dose and 18 (29.0%) patients discontinued afatinib due to treatment-related adverse effects. There were no drug-related deaths.
Noting that there is a growing need for new molecular targeted agents that address the issue of resistance to erlotinib and gefitinib, Katakami and co-authors say that afatinib has shown “modest but noteworthy efficacy.”
They write: “Further evaluation of the potential of afatinib in patients with advanced NSCLC will be addressed by the LUX-Lung phase III clinical trial program and the ongoing study of the afatinib plus cetuximab combination in the resistance setting.”
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
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http://www.ncbi.nlm.nih.gov/pubmed/22452896FINDINGS:
Between May 26, 2008, and Sept 21, 2009, we identified 697 patients, 585 of whom were randomly allocated to treatment (390 to afatinib, 195 to placebo). Median overall survival was 10·8 months (95% CI 10·0-12·0) in the afatinib group and 12·0 months (10·2-14·3) in the placebo group (hazard ratio 1·08, 95% CI 0·86-1·35; p=0·74). Median progression-free survival was longer in the afatinib group (3·3 months, 95% CI 2·79-4·40) than it was in the placebo group (1·1 months, 0·95-1·68; hazard ratio 0·38, 95% CI 0·31-0·48; p<0·0001). No complete responses to treatment were noted; 29 (7%) patients had a partial response in the afatinib group, as did one patient in the placebo group. Subsequent cancer treatment was given to 257 (68%) patients in the afatinib group and 153 (79%) patients in the placebo group. The most common adverse events in the afatinib group were diarrhoea (339 [87%] of 390 patients; 66 [17%] were grade 3) and rash or acne (305 [78%] patients; 56 [14%] were grade 3). These events occurred less often in the placebo group (18 [9%] of 195 patients had diarrhoea; 31 [16%] had rash or acne), all being grade 1 or 2. Drug-related serious adverse events occurred in 39 (10%) patients in the afatinib group and one (<1%) patient in the placebo group. We recorded two possibly treatment-related deaths in the afatinib group.
INTERPRETATION:
Although we recorded no benefit in terms of overall survival with afatinib (which might have been affected by cancer treatments given after progression in both groups), our findings for progression-free survival and response to treatment suggest that afatinib could be of some benefit to patients with advanced lung adenocarcinoma who have failed at least 12 weeks of previous EGFR tyrosine-kinase inhibitor treatment. |
奥希替尼并非肺癌“万能解”，患者如
作者：Tony
在肺癌中，EGFR的突变以19号外显子缺失突变（19Del）和21号外显子的L858R
【基因检测，人人可及】肿瘤患者免费
【基因检测，人人可及】肿瘤患者免费基因检测公益援助
与癌共舞论坛联手吉因加推出的
明天二化开始，今天化疗天检查
一化前的指标：
肝肾功能都正常，肺癌七项CA-125偏高，其他正常，D-二聚体4.67，正常
奥西替尼副作用
病人egfr19+pik3ca突变，2024年5月30号开始服用奥西替尼，到6月28号刚好30天，肿瘤大
百泽安®️三项研究ESMO IO重磅更新
作者：seacat
百泽安®️（替雷利珠单抗）是患者较为熟悉的国产PD-1单抗，由百济神州
显身卡
