Erlotinib in advanced non-small-cell lung cancer after gefitinib failure

Purpose  To evaluate the efficacy and safety of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib treatment. Patients and methods  Patients with advanced or metastatic NSCLC, who had progressed after gefitinib treatment, were included in this study; patients received erlotinib 150 mg/day until disease progression or intolerable toxicity. Results  Twenty-one patients were included in this study. Among them, 14 (66.7%) were male and 7 (33.3%) were female; median age was 63 years; 10 (47.6%) patients were smokers; 9 (42.9%)patients had squamous cell carcinoma subtype; 8 (38.1%) patients had adenocarcinoma subtype and 4 (19%) patients had the other NSCLC subtype. Out of 21 patients, 2 (9.5%) had PR and 4 (19.0%) had SD, giving an overall response rate of 9.5% and a disease control rate of 28.5%. The median TTP were 55 days, the median OS were 135 days. Two patients with PR to erlotinib treatment were female never smokers with adenocarcinoma histology and both had partial response to prior gefitinib treatment. Three of four patients with a SD to erlotinib treatment also had SD from prior gefitinib therapy. Smoking history, histology and response to erlotinib were significantly correlated with survival. The most common toxic effects were skin rash. Conclusions  Erlotinib may be an option for a more highly selected subset of patients, especially those who had already benefited from prior gefitinib treatment.     

CT findings in non-small-cell lung cancer patients treated with gefitinib or erlotinib

Purpose: We performed this study to explore the association of computed tomography (CT) findings with outcomes of patients with non-small-cell lung cancer (NSCLC) treated with tyrosin kinase inhibitor (TKI) such as gefitinib or erlotinib. Materials and Methods: We analyzed outcomes for 240 patients according to primary tumor (T), regional nodal (N) staging and diffuse small pulmonary metastases (DSPM) at the initial presentation. Tests for epidermal growth factor receptor (EGFR) mutation were performed in 92 patients. Results: On multivariate analysis for tumor response, the N3 stage was predictive of a poor response (P < 0.001), whereas DSPM was a favorable factor (P = 0.007). Multivariate analysis for progression-free survival showed that the T3-4 stage (hazard ratio [HR]: 2.5, P < 0.001), in addition to the N3 stage (HR: 2.1, P < 0.001), was predictive of a poor outcome, whereas DSPM (HR: 0.6, P = 0.006) was a favorable factor. Notably, the multivariate model that included the EGFR mutational status revealed that the T3-4 stage predicted poor progression-free survival (HR: 2.2, P = 0.017) and poor overall survival (HR: 4.1, P < 0.001). Conclusion: Our data suggest that, in addition to EGFR mutational status, T-stage based on CT is predictive of outcomes of TKI-treated NSCLC patients.     

Phase II study of erlotinib as a salvage treatment for non-small-cell lung cancer patients after failure of gefitinib treatment

Background: Both gefitinib and erlotinib are reversible epidermal growth factor receptor tyrosine kinase inhibitors, but they have somewhat different pharmacological properties. We conducted a phase II study of erlotinib after failure of gefitinib treatment in patients with non-small-cell lung cancer (NSCLC).Patients and methods: Patients with advanced/metastatic NSCLC who had shown disease progression on gefitinib treatment were treated with erlotinib 150 mg/day until disease progression or intolerable toxicity.Results: Between September 2006 and January 2008, a total of 23 patients were enrolled and all were assessable for response and toxicity. All patients were never smokers and all but one had adenocarcinoma. Of these 23 patients, one had a partial response and one stable disease, resulting in an objective response rate of 4.3% and a disease control rate of 8.7%. These two patients benefited from erlotinib for 6.2 months and 7.8 months, respectively; both had also benefited from prior gefitinib therapy. The most common toxic effects were skin rash and diarrhea.Conclusion: Erlotinib should not be given routinely after failure of gefitinib treatment, but can be an option for more highly selected subsets, especially those who had benefited from prior gefitinib treatment. Identification of molecular markers in tumors is important to understand and overcome acquired resistance to gefitinib.     

Safety profiles of erlotinib therapy in patients with advanced non-small-cell lung cancer

Erlotinib is an orally available, small-molecule EGF receptor tyrosine kinase inhibitor. It has shown promising activity in chemotherapy-relapsed patients with advanced non-small-cell lung cancer and is now approved in many countries. To date, there have been a number of clinical studies of erlotinib therapy demonstrating its safety as well as its efficacy. This article summarizes clinical study results in advanced non-small-cell lung cancer, so that we can comprehensively understand the toxicities expected with erlotinib in non-small-cell lung cancer patients.     

Comparison of gefitinib and erlotinib efficacies as third-line therapy for advanced non-small-cell lung cancer

PurposeThe epidermal growth factor receptor inhibitors, gefitinib and erlotinib, are used as standard salvage therapy for advanced non-small-cell lung cancer (NSCLC). The aim of the present study was to compare their efficacies in this population.Patients and methodsThe Taiwan Cancer Registry and the National Health Insurance claim databases were searched for newly diagnosed patients with NSCLC from 2004 to 2007 who received gefitinib or erlotinib as third-line therapy. Overall survival (OS) and time to treatment failure (TTF) were determined from registered parameters. Treatment efficacies were compared by the log-rank test in total population and subsets with different clinical characteristics. The Cox’s proportion hazard model was used to estimate the adjusted hazard ratios in multivariate analyses.ResultsA total of 984 patients who received gefitinib (67%) or erlotinib (33%) were included. Patients receiving gefitinib or erlotinib had similar OS (median, 10.2 versus 9.9 months, p = 0.524) and TTF (median, 5.5 versus 3.4 months, p = 0.103). In multivariate analyses, both treatment groups had similar risk of overall mortality (adjusted hazard ratio [HR] = 1.04, p = 0.629) and treatment failure (adjusted HR = 0.94, p = 0.417). Comparing the treatments in subgroups based on age, tumour histology and gender also revealed no differences in OS and TTF. For patients who received gefitinib or erlotinib for more than 3 or 6 months, there was no difference in TTF but patients who received erlotinib had longer OS.ConclusionsGefitinib and erlotinib had similar efficacies as salvage therapy for advanced NSCLC in Taiwan.     

Prospective study of gefitinib readministration after chemotherapy in patients with advanced non-small-cell lung cancer who previously responded to gefitinib

IntroductionSalvage treatment for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in patients with non–small-cell lung cancer is a matter of clinical concern. Several retrospective reports have indicated the usefulness of epidermal growth factor receptor tyrosine kinase inhibitor readministration; however, there have been few prospective studies.Materials and MethodsThis study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced or metastatic non–small-cell lung cancer who responded well to initial gefitinib treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy after progressive disease with the initial gefitinib therapy. Gefitinib administration (250 mg/d, orally) was started after progressive disease with the previous chemotherapeutic regimen. The primary endpoint in the present study was the response rate.ResultsTwenty patients were enrolled between April 2007 and May 2011. Three patients achieved partial response, and 6 showed stable disease. Thus, the overall response rate and disease control rate of gefitinib readministration were 15% (95% CI, 3.21-37.9) and 45% (95% CI, 23.1-68.5), respectively. Median progression-free survival and overall survival from the start of gefitinib readministration were 2.0 months (95% CI, 0.9-3.1 months) and 12.0 months (95% CI, 8.0-16.0 months), respectively.ConclusionThese results suggest that gefitinib readministration may be an option, albeit with a low response rate and short progression-free survival, for patients who responded well to initial gefitinib followed by systemic chemotherapy. These findings provide valuable information for the management of previous gefitinib responders.     

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

Background

Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient.

Purpose

To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC), a study of single agent treatment with gefitinib in Chinese patients was conducted.

Methods

45 patients with advanced NSCLC were treated with gefitinib (250 mg daily) until the disease progression or intolerable toxicity.

Results

Among the 45 patients, 15 patients achieved partial response (PR), 17 patients experienced stable disease (SD), and 13 patients developed progression disease (PD). None of the patients achieved complete response (CR). The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively). The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively). In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively).

Conclusions

Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

     

厄罗替尼治疗晚期非小细胞肺癌19例临床疗效

目的评价厄罗替尼治疗ⅢB～Ⅳ期非小细胞肺癌（NSCLC）的疗效和患者不良反应。方法19例患者均为经病理证实的、至少接受过一种方案全身化疗的晚期NSCLC患者。厄罗替尼150mg／次,1次／d,口服,直至病情进展或出现不能耐受的不良反应。采用实体瘤疗效评价标准（RECIST）评价疗效,美国国立癌症研究所毒性评价标准（CTCAE）评价不良反应。结果19例患者客观缓解率（ORR）为21．1％（4／19）。疾病控制率（完全缓解＋部分缓解＋稳定）为84．2％（16／19）,疾病无进展生存时间（PFS）3～36个月,中位PFS7．5个月;生存时间9～39个月,中位生存时间15．9个月。不良反应主要是皮疹16例（84．2％）,腹泻11例（57．9％）,多为Ⅰ～Ⅱ度;Ⅲ度丙氨酸氨基转移酶升高1例;未出现Ⅳ度药物相关不良反应。结论厄罗替尼对既往化疗失败的局部晚期或转移性NSCLC患者有较好的疗效和安全性。     

一线化疗后吉非替尼维持治疗晚期非小细胞肺癌的临床观察

Objective To evaluate RR,DCR,PFS,OS and toxicities in a population affected by NSCLC using gefitinib as maintenance therapy after the first line chemotherapy.Methods From January,2006 to January,2008,seventy-one patients were enrolled with stable disease or partial response after firstline chemotherapy.They were divided into the observing group and the control group.Gefitinib was administered at the dose of 250 mg in observing group;placebo was also administered everyday in control group.Results Of 71 assessable patients ,overall response rate was 36.1% (13/36) in observing group and 14.3 % (5/35) in control group respectively (x 2 = 4.633,P = 0.036),and one patient (2.8 %) was observed complete response (CR) in observing group.The disease control rate was 83.3 % (30/36) in observing group and 42.9 % (15/35) in control group,respectively,(x2 = 14.782,P ＜ 0.001).The median PFS (progression free survival time) was 13 weeks in observing group and 11 weeks in control group respectively (x2 = 10.401,P =0.001).The median overall survival time (OS) was 13.2 months in observing group and 10.4 months in control group respectively (x2 = 7.696,P= 0.006).The median OS was 18.5 months in women and 11.2 months in men(x2 =22.864,P=0.011) .The median OS was 15.3 months in non-smokers and 10.3 months in smokers (x2 =10.389,P =0.007).The median OS was 16.0 months in adenocarcinoma and alveolar cell carcinoma patients and 10.2 months in squamous cell carcinoma patients (x 2 = 4.638,P = 0.001).The most common toxicity was rash ,diarrhea,fatigue and dry skin itching,and most of them were 1 or 2 grade.Conclusion Maintenance therapy with gefitinib after first-line chemotherapy may improve overall survival time and progression free survival time in patients with NSCLC,and it is effective and safe.     

一线化疗后吉非替尼维持治疗晚期非小细胞肺癌的临床观察

 【摘要】　目的　评价晚期非小细胞肺癌（NSCLC）一线化疗获得部分缓解（PR）或稳定（SD）后予以吉非替尼单药维持治疗的临床疗效。方法　应用前瞻性随机对照临床研究方法,将71例经标准的两药含铂方案一线化疗获得PR或SD的患者按随机数字表法分为两组,治疗组患者（36例）服用吉非替尼250 mg,1次／d;对照组（35例）服用安慰剂,1次／d。两组患者均服用至疾病进展。结果　治疗组总有效率（RR）为36.1 %（13／36）,其中1例（2.8 %）完全缓解（CR）,对照组RR为14.3 %（5／35）,两组差异有统计学意义（χ2＝4.633,P＝0.036）。治疗组疾病控制率（CR+PR+SD,DCR）为83.3 %（30／36）,对照组为42.9 %（15／35）,两组差异有统计学意义（χ2＝14.782,P＜0.001）。治疗组无进展生存期（PFS）较安慰剂组显著延长（分别为13周和11周）（χ2＝10.401,P＝0.001）。治疗组中位生存期（OS）为13.2个月,对照组为10.4个月,两组差异有统计学意义（χ2＝7.696,P＝0.006）。治疗组女性患者中位OS（18.5个月）显著长于男性（11.2个月）（χ2＝22.864,P＝0.011）;不吸烟者中位OS（15.3个月）亦长于吸烟者（10.3个月）（χ2＝0.389,P＝0.007）;腺癌及肺泡细胞癌患者中位OS（16.0个月）亦显著长于鳞状细胞癌患者（10.2个月）（χ2＝4.638,P＝0.001）。治疗组不良反应以皮疹、腹泻、皮肤干燥瘙痒及乏力为主,多为Ⅰ、Ⅱ度。结论　晚期NSCLC一线化疗后吉非替尼维持治疗可以提高疗效、延长患者生存期,不良反应轻,可以耐受。     

一线化疗后吉非替尼维持治疗晚期非小细胞肺癌的临床观察

Objective To evaluate RR,DCR,PFS,OS and toxicities in a population affected by NSCLC using gefitinib as maintenance therapy after the first line chemotherapy.Methods From January,2006 to January,2008,seventy-one patients were enrolled with stable disease or partial response after firstline chemotherapy.They were divided into the observing group and the control group.Gefitinib was administered at the dose of 250 mg in observing group;placebo was also administered everyday in control group.Results Of 71 assessable patients ,overall response rate was 36.1% (13/36) in observing group and 14.3 % (5/35) in control group respectively (x 2 = 4.633,P = 0.036),and one patient (2.8 %) was observed complete response (CR) in observing group.The disease control rate was 83.3 % (30/36) in observing group and 42.9 % (15/35) in control group,respectively,(x2 = 14.782,P ＜ 0.001).The median PFS (progression free survival time) was 13 weeks in observing group and 11 weeks in control group respectively (x2 = 10.401,P =0.001).The median overall survival time (OS) was 13.2 months in observing group and 10.4 months in control group respectively (x2 = 7.696,P= 0.006).The median OS was 18.5 months in women and 11.2 months in men(x2 =22.864,P=0.011) .The median OS was 15.3 months in non-smokers and 10.3 months in smokers (x2 =10.389,P =0.007).The median OS was 16.0 months in adenocarcinoma and alveolar cell carcinoma patients and 10.2 months in squamous cell carcinoma patients (x 2 = 4.638,P = 0.001).The most common toxicity was rash ,diarrhea,fatigue and dry skin itching,and most of them were 1 or 2 grade.Conclusion Maintenance therapy with gefitinib after first-line chemotherapy may improve overall survival time and progression free survival time in patients with NSCLC,and it is effective and safe.     

A phase II trial of erlotinib in patients with EGFR wild-type advanced non-small-cell lung cancer

Purpose

There is as yet no optimal treatment regimen for patients with epidermal growth factor receptor (EGFR) gene wild-type non-small-cell lung cancer (NSCLC) that has progressed despite cytotoxic chemotherapy. This trial was performed to evaluate the efficacy and toxicity of erlotinib, a tyrosine kinase inhibitor of EGFR, in Japanese patients with EGFR wild-type tumors.

Methods

Patients with stage III/IV or postoperative recurrence of NSCLC whose tumors have wild-type EGFR were eligible. Erlotinib (150?mg/day) was administered until disease progression or unacceptable toxicity occurred. The primary end point was disease control rate (DCR).

Results

Thirty-one patients (23 men and 8 women; median age, 71?years; range, 31–89) were enrolled between January 2008 and June 2011. Twenty-one had adenocarcinoma, nine had squamous cell carcinoma, and one had large cell carcinoma. Ten, nine, eight, and four patients showed performance status 0, 1, 2, and 3, respectively. Erlotinib was administered following the median 3.1 regimens of cytotoxic chemotherapies. One patient achieved complete response, four showed partial response, and eight had stable disease. Thus, response rate was 17.2%, and DCR was 44.8%. Skin rash was the most common side effect (80.6%). Two patients developed interstitial lung disease. Nevertheless, all of these events were reversible, and there were no treatment-related deaths. The median progression-free survival and survival times were 2.1 and 7.7?months, respectively.

Conclusion

Erlotinib might be an alternative option for patients resistant to cytotoxic chemotherapy even in those with EGFR wild-type NSCLC.     

Second-line erlotinib in patients with advanced non-small-cell lung cancer: subgroup analyses from the TRUST study

Erlotinib is a highly potent inhibitor of epidermal growth factor receptor tyrosine-kinase activity that significantly prolongs overall survival in patients with non-small-cell lung cancer (NSCLC), and improves symptom control and quality of life compared with placebo. The safety and efficacy of erlotinib has been investigated in a large, international, phase IV, open-label study (TRUST) in patients (n = 6665) with advanced stage IIIB/IV NSCLC. An analysis of efficacy and safety outcomes is reported for patients receiving erlotinib as second-line therapy in TRUST (n = 3224). Best response data were available for all 3224 patients. Complete response, partial response and stable disease were achieved in 25 (<1%), 368 (14%) and 1444 (54%) patients, respectively, for a disease control rate of 68%. Median progression-free and overall survivals were 13.6 weeks and 8.6 months, respectively; 1-year survival was 39.4%. Safety data were available for all patients. Of these, 389 patients (12%) had an erlotinib-related adverse event (AE) other than pre-specified AEs defined in the protocol; only 96 patients (3%) had an erlotinib-related AE ≥grade 3. Of 1376 patients (43%) with serious AEs (SAEs), only 122 (4%) had treatment-related SAEs and most were gastrointestinal disorders (mainly diarrhoea and nausea). No treatment-related SAE occurred in ≥1% of patients. Data on the incidence of erlotinib-related rash were collected for all patients, 2302 (71%) of whom experienced rash. Of these rash events, 83% were of grade 1/2. These data confirm the good efficacy and tolerability of second-line erlotinib in a broad range of patients with NSCLC.Clinical trial number: NCT00949910.     

厄洛替尼治疗吉非替尼耐药的进展期非小细胞肺癌的临床观察

目的　评价厄洛替尼对吉非替尼耐药的进展期非小细胞肺癌（ＮＳＣＬＣ）患者的疗效和安全性。方法　回顾性分析２００６年６月至２００９年２月１５例ＮＳＣＬＣ患者,均口服吉非替尼并出现病情进展,改换为厄洛替尼１５０ｍｇ,１次／日,直到病情进展或不良反应不能耐受为止。观察疗效、不良反应以及疗效与临床特征之间的关系。结果　厄洛替尼治疗吉非替尼耐药共１５例进展期ＮＳＣＬＣ患者,１例获得ＰＲ,４例获得ＳＤ,客观有效率为６.７％,疾病控制率为３３.３％。获有效和稳定的５例患者中４例曾吉非替尼治疗获益。厄洛替尼治疗的中位疾病进展期（ＴＴＰ）和中位总生存期（ＯＳ）分别为１１１天和２２３天。厄洛替尼获益的５例患者较未获益的１０例患者获得更长的ＴＴＰ（１１１天ｖｓ．３５.５天,Ｐ＜０.０５）。厄洛替尼最常见的副反应为轻度皮疹和腹泻。结论　厄洛替尼似乎是治疗吉非替尼耐药的进展期ＮＳＣＬＣ的有效药物,尤其是对于曾予吉非替尼治疗可以获益的患者,但厄洛替尼不应作为常规的二线选择,对患者谨慎筛选很有必要。