Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancers?

To examine whether weight loss at presentation influences outcome in patients who received chemotherapy for lung cancer or mesothelioma. Multivariate analysis of prospectively collected data 1994-2001. Data were available for age, gender, performance status, histology, stage, response, toxicity, progression-free and overall survival. The outcomes of patients with or without weight loss treated with chemotherapy for small cell lung cancer (SCLC; n=290), stages III and IV non-small-cell lung cancer (NSCLC; n=418), or mesothelioma (n=72) were compared. Weight loss was reported by 59, 58 and 76% of patients with SCLC, NSCLC and mesothelioma, respectively. Patients with weight loss and NSCLC (P=0.003) or mesothelioma (P=0.05) more frequently failed to complete at least three cycles of chemotherapy. Anaemia as a toxicity occurred significantly more frequently in NSCLC patients with weight loss (P=0.0003). The incidence of other toxicities was not significantly affected by weight loss. NSCLC patients with weight loss had fewer symptomatic responses (P=0.001). Mesothelioma patients with weight loss had fewer symptomatic (P=0.03) and objective responses (P=0.05). Weight loss was an independent predictor of shorter overall survival for patients with SCLC (P=0.003, relative risk (RR)=1.5), NSCLC (P=0.009, RR=1.33) and mesothelioma (P=0.03, RR=1.92) and an independent predictor of progression-free survival in patients with SCLC (P=0.01, RR=1.43). In conclusion, weight loss as a symptom of lung cancer predicts for toxicity from treatment and shorter survival.     

Wait Times and Survival in Lung Cancer Patients across the Province of Quebec,Canada

Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017. Patients were followed for 3 years. Wait times for diagnosis and treatment were collected, and survival analysis using a Cox regression model was conducted. We included 1309 patients, of whom 39% had stage IV non-small cell lung cancer (NSCLC). Median wait times were, in general, significantly shorter in patients with stage III–IV NSCLC or SCLC. Surgery was associated with delays compared to other types of treatments. Median survival was 12.9 (11.1–15.7) months. The multivariate survival model included age, female sex, performance status, histology and stage, treatment, and the time interval between diagnosis and treatment. Longer wait times had a slightly protective to neutral effect on survival, but this was not significant in the stage I–II NSCLC subgroup. Wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced NSCLC and SCLC might indicate a tendency for clinicians to act quicker on sicker patients. This study did not demonstrate the detrimental effect of longer wait times on survival.     

Clinical impact of amphiregulin expression in patients with epidermal growth factor receptor (EGFR) wild‐type nonsmall cell lung cancer treated with EGFR‐tyrosine kinase inhibitors

BACKGROUND:

In patients with nonsmall cell lung cancer (NSCLC), several studies have demonstrated a positive correlation between somatic mutation in the epidermal growth factor receptor (EGFR) tyrosine kinase domain and clinical outcomes with the use of EGFR tyrosine kinase inhibitors (TKIs). However, some patients with wild‐type (WT) EGFR also responded to EGFR TKIs and remained stable. Recently, amphiregulin (AR) has been suggested as a predictive marker for EGFR TKIs in patients with WT EGFR‐positive NSCLC. The objective of the current study was to evaluate the association between AR expression and the efficacy of using EGFR TKIs in the treatment of patients with WT EGFR‐positive NSCLC.

METHODS:

Seventy‐three patients with WT EGFR‐positive NSCLC received treatment with gefitinib or erlotinib between May 2005 and December 2008. AR expression was assessed by immunohistochemistry.

RESULTS:

The clinical response to EGFR TKIs was reassessed for all patients as follows: 16 of 73 patients had a partial response (21.9%), 12 patients had stable disease (16.5%), and 45 patients had progressive disease (61.6%). AR expression was positive in 24 of 40 patients (60%). The ability to achieve disease control did not differ significantly between AR‐positive patients and AR‐negative patients (P = .188). At a median follow‐up of 25.4 months (range, 10.5‐53.3 months), progression‐free survival was 8.1 weeks in AR‐positive patients and 4 weeks in AR‐negative patients (P = .025), and overall survival was significantly longer in AR‐positive patients than in AR‐negative patients (12.2 months vs 4.1 months; P = .001).

CONCLUSIONS:

The current results suggested that patients with WT EGFR‐positive NSCLC who have AR‐positive tumors may benefit clinically from treatment with EGFR TKIs, indicating that AR expression may be a potential marker for the selection of EGFR‐TKI treatment for patients with WT EGFR‐positive NSCLC. Cancer 2011. © 2010 American Cancer Society.     

Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010–2016 in Sweden: A nationwide observational study

The purpose of our study was to investigate time trends in treatment pattern and prognostic factors for overall survival (OS) in epidermal growth factor receptor (EGFR) targeting tyrosine kinase inhibitors (TKIs) treated nonsmall cell lung cancer (NSCLC) patients. Utilizing Swedish nationwide registers, we identified all Stage IIIB–IV NSCLC patients treated with EGFR TKIs and followed them from diagnosis (2010–2015) until death or end of observation (2016). Multivariable Cox regression analyses were performed to test associations of patient-, tumor-related factors with OS. Of 9,992 Stage IIIB–IV NSCLC patients, the 1,419 (14%) who initiated EGFR TKI treatment during observation were younger (median age 68 vs. 71 years), less ≥1 comorbidities (34% vs. 46%), more often female (59% vs. 47%), Stage IV (89% vs. 85%) and adenocarcinoma (85% vs. 66%) compared to non-TKI treated patients. After TKI initiation, 7% (n = 100) of the patients switched, 4% (n = 62) rechallenged a TKI treatment, 65% (n = 919) discontinued and 24% (n = 338) had died. A more recent diagnosis demonstrated shorter time to EGFR TKI initiation, prolonged treatment length and longer median OS (15.3 months 2010–2011; 14.4 months 2012–2013; 18.6 months 2014–2015). Prognostic factors for longer OS when treated with EGFR TKIs were younger age, adenocarcinoma, less advanced clinical stage and less comorbid disease. In conclusion, during the observation period, survival improved for EGFR TKI treated NSCLC patients, as did the accessibility for targeted therapies for these patients.     

Osimertinib for Japanese patients with T790M‐positive advanced non‐small‐cell lung cancer: A pooled subgroup analysis

Epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) are the standard of care for non‐small‐cell lung cancer (NSCLC) patients harboring EGFR mutations. However, almost all patients develop resistance after approximately 1 y of treatment, with >50% of cases due to the T790M secondary mutation of the EGFR gene. A large global Phase III study (AURA3) demonstrated that osimertinib significantly prolonged progression‐free survival (PFS) over platinum‐doublet chemotherapy in patients with T790M‐positive NSCLC who had progressed on previous EGFR‐TKI therapy. However, it is not clear whether efficacy or safety of osimertinib in Japanese patients is similar to the overall population. We report a pre‐planned subgroup analysis of pooled Phase II data from the AURA Extension and AURA2 trials to investigate the efficacy and safety of osimertinib in Japanese patients. This study included 81 Japanese patients. Patients were administered 80 mg osimertinib orally once daily until disease progression. The main endpoints were objective response rate (ORR), PFS, and safety. The ORR was 63.6% and median PFS was 13.8 mo. Overall survival rate at 36 mo was 54.0%. The most common all‐cause adverse events (AEs) were rash (grouped term; 65.4%), diarrhea (51.9%), paronychia (grouped term; 49.4%), and dry skin (grouped term; 39.5%). Most AEs were grade 1‐2. Five patients (6.2%) developed interstitial lung disease, resulting in two deaths (2.5%). Osimertinib demonstrated favorable ORR and PFS in Japanese patients, similar to the overall population. Additionally, osimertinib has good efficacy and a manageable safety profile in Japanese patients with NSCLC who had acquired resistance due to the T790M mutation.     

Comparison of gefitinib,erlotinib and afatinib in non‐small cell lung cancer: A meta‐analysis

Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non‐small cell lung cancer (NSCLC) with proven efficacy. We undertook a systematic review and meta‐analysis to synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety. Eight randomized trials and 82 cohort studies with a total of 17,621 patients were included for analysis. Gefitinib and erlotinib demonstrated comparable effects on progression‐free survival (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.95 to 1.04), overall survival (HR, 0.99; 95% CI, 0.93 to 1.06), overall response rate (risk ratio [RR], 1.05; 95% CI, 1.00 to 1.11), and disease control rate (RR, 0.98; 95% CI, 0.96 to 1.01), which did not vary considerably with EGFR mutation status, ethnicity, line of treatment, and baseline brain metastasis status. Gefitinib was associated with more grade 3/4 liver dysfunction, but tended to cause lower rates of dose reduction, treatment discontinuation, total grade 3/4 adverse events (RR, 0.78; 95% CI 0.65 to 0.94), and a number of specific adverse events such as rash and diarrhea. No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first‐line treatment of EGFR‐mutant NSCLC. However, afatinib was more effective than erlotinib as second‐line treatment of patients with advanced squamous cell carcinoma. The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib.     

Enhanced gefitinib‐induced repression of the epidermal growth factor receptor pathway by ataxia telangiectasia‐mutated kinase inhibition in non‐small‐cell lung cancer cells

The epidermal growth factor receptor (EGFR) tyrosine kinase signaling pathways regulate cellular activities. The EGFR tyrosine kinase inhibitors (EGFR‐TKIs) repress the EGFR pathway constitutively activated by somatic EGFR gene mutations and have drastically improved the prognosis of non‐small‐cell lung cancer (NSCLC) patients. However, some problems, including resistance, remain to be solved. Recently, combination therapy with EGFR‐TKIs and cytotoxic agents has been shown to improve the prognosis of NSCLC patients. To enhance the anticancer effects of EGFR‐TKIs, we examined the cross‐talk of the EGFR pathways with ataxia telangiectasia‐mutated (ATM) signaling pathways. ATM is a key protein kinase in the DNA damage response and is known to phosphorylate Akt, an EGFR downstream factor. We found that the combination of an ATM inhibitor, KU55933, and an EGFR‐TKI, gefitinib, resulted in synergistic cell growth inhibition and induction of apoptosis in NSCLC cell lines carrying the sensitive EGFR mutation. We also found that KU55933 enhanced the gefitinib‐dependent repression of the phosphorylation of EGFR and/or its downstream factors. ATM inhibition may facilitate the gefitinib‐dependent repression of the phosphorylation of EGFR and/or its downstream factors, to exert anticancer effects against NSCLC cells with the sensitive EGFR mutation.     

非小细胞肺癌EGFR-TKIs耐药——小细胞肺癌转化的机制和治疗

肺癌是当前死亡率最高的恶性肿瘤之一。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）明显提高了晚期非小细胞肺癌（NSCLC）患者的生活质量,延长了生存期。EGFR基因优势突变的NSCLC患者临床获益明显,然而由于耐药产生,患者的中位无进展生存期（PFS）仅1年左右。最近,有文献报道EGFR TKIs耐药的机制之一是NSCLC转化为小细胞肺癌（SCLC）。本文对这种现象进行了分析总结,探讨了其转化的可能机制。根据EGFR-TKIs耐药后的处理方法和病理表型转化患者的治疗报道,探讨NSCLC EGFR-TKIs耐药后转化为SCLC患者的治疗策略。     

First-line therapy and methylation status of CHFR in serum influence outcome to chemotherapy versus EGFR tyrosine kinase inhibitors as second-line therapy in stage IV non-small-cell lung cancer patients

The potential differential effect of first-line treatment and molecular mechanisms on survival to second-line chemotherapy or EGFR tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) has not been fully investigated. In particular, CHFR is frequently methylated in NSCLC and may influence outcome. We analyzed the outcome of second-line chemotherapy or EGFR TKIs in 179 of 366 patients who had been treated in an ERCC1 mRNA-based customized cisplatin trial and correlated the results with CHFR methylation status. CHFR methylation in circulating DNA was examined by methylation-specific assay. A panel of seven human EGFR wild-type NSCLC cell lines was characterized for their sensitivity to sequential treatment with cisplatin and erlotinib, and the results were correlated with CHFR. Patients who had received first-line docetaxel/cisplatin attained an overall survival of 19.2 months when treated with second-line EGFR TKIs, in comparison with 10.7 months when treated with second-line chemotherapy (P = 0.0002). However, for patients who had received first-line docetaxel/gemcitabine, overall survival was 14.8 months with EGFR TKIs and 10.8 months with chemotherapy (P = 0.29). For patients with unmethylated CHFR overall survival to EGFR TKIs was 21.4 months, and 11.2 months for those with treated with chemotherapy (P = 0.0001). In the only lung tumor cell line not expressing CHFR, pretreatment with cisplatin was antagonistic to erlotinib, while it was synergistic in the other six lines. Second-line EGFR TKIs improved survival in patients receiving first-line cisplatin-based treatment. Unmethylated CHFR predicts increased survival to EGFR TKIs.     

Retracted: Genistein enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitors and inhibits nuclear factor kappa B in nonsmall cell lung cancer cell lines

BACKGROUND:

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have shown modest clinical benefit in patients with relapsed nonsmall cell lung cancer (NSCLC). Down‐regulation of Akt appears to correlate with the antitumor activity of EGFR‐TKIs. Akt activates nuclear factor kappa B (NF‐κB), which transcribes genes important for cell survival, invasion, and metastasis. The authors hypothesized that genistein, through the inhibition of NF‐κB, could enhance the activity of EGFR‐TKIs in NSCLCs.

METHODS:

Three NSCLC cell lines with various EGFR mutation status and sensitivities to EGFR‐TKIs were selected: H3255 (L858R), H1650 (del E746‐A750), and H1781 (wild‐type EGFR). Cells were treated with erlotinib, gefitinib, genistein, or the combination of each of the EGFR‐TKIs with genistein. Cell survival and apoptosis were assessed, and expression levels of EGFR, pAkt, cyclooxygenase‐2 (COX‐2), E‐cadherin, prostaglandin E₂ (PGE₂), and NF‐κB were measured.

RESULTS:

Both EGFR‐TKIs demonstrated growth inhibition and apoptosis in each of the cell lines, but H1650 and H1781 were much less sensitive. Genistein demonstrated some antitumor activity in all cell lines, but enhanced growth inhibition and apoptosis when combined with the EGFR‐TKIs in each of the cell lines. Both combinations down‐regulated NF‐κB significantly more than either agent alone in H3255. In addition, the combinations reduced the expression of EGFR, pAkt, COX‐2, and PGE_2, consistent with inactivation of NF‐κB.

CONCLUSIONS:

The authors concluded that genistein enhances the antitumor effects of EGFR‐TKIs in 3 separate NSCLC cell lines. This enhanced activity is in part because of greater reduction in the DNA‐binding activity of NF‐κB when EGFR‐TKIs were combined with genistein. Cancer 2009. © 2009 American Cancer Society.     

High grade neuroendocrine lung tumors: Pathological characteristics,surgical management and prognostic implications

Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC.     

Small cell lung cancer: Where do we go from here?

Small cell lung cancer (SCLC) is an aggressive disease that accounts for approximately 14% of all lung cancers. In the United States, approximately 31,000 patients are diagnosed annually with SCLC. Despite numerous clinical trials, including at least 40 phase 3 trials since the 1970s, systemic treatment for patients with SCLC has not changed significantly in the past several decades. Consequently, the 5‐year survival rate remains low at <7% overall, and most patients survive for only 1 year or less after diagnosis. Unlike nonsmall cell lung cancer (NSCLC), in which major advances have been made using targeted therapies, there are still no approved targeted drugs for SCLC. Significant barriers to progress in SCLC include 1) a lack of early detection modalities, 2) limited tumor tissue for translational research (eg, molecular profiling of DNA, RNA, and/or protein alterations) because of small diagnostic biopsies and the rare use of surgical resection in standard treatment, and 3) rapid disease progression with poor understanding of the mechanisms contributing to therapeutic resistance. In this report, the authors review the current state of SCLC treatment, recent advances in current understanding of the underlying disease biology, and opportunities to advance translational research and therapeutic approaches for patients with SCLC. Cancer 2015;121:664–672. © 2014 American Cancer Society.     

Five‐year lung cancer survival

BACKGROUND:

The core strategy of American College of Chest Physicians lung cancer guidelines is identification of the earliest symptoms of lung cancer and the immediate initiation of diagnosis and treatment. In the absence of screening, most symptomatic lung cancer is discovered at advanced stages, with the goal of long‐term survival entirely dependent on effective treatment of stage III and IV lung cancer.

METHODS:

In a retrospective review, all patients diagnosed with stage IIIA, IIIB, and IV nonsmall cell lung cancer (NSCLC) between the years 1986 and 2001 at City of Hope National Medical Center who survived 5 years or longer were analyzed to identify parameters that might predict long‐term survival.

RESULTS:

Of 846 patients presenting with stage III or IV disease, 56 (6.6%) survived 5 years or longer. Sixteen patients died of primary tumor progression beyond 5 years. Two 5‐year survivors died of second tobacco‐caused neoplasms, and 16 died from medical conditions potentially related to prior treatment. A substantial majority of survivors were from specific pathologic subsets including: 1) resectable N2 disease (n = 17, 30.4%), 2) multiple lung tumors (n = 7, 12.5%), 3) T3N0 (n = 5, 8.1%), and 4) single site distant metastasis (n = 8, 14.2%).

CONCLUSIONS:

Despite aggressive multimodality therapy, 5‐year survival in patients with advanced stage NSCLC was very poor and limited to small pathological subsets. Patients with advanced stage NSCLC who did not belong to 1 of these subsets had a small chance of long‐term survival. Cancer 2010. © 2010 American Cancer Society.     

Personalizing therapy with targeted agents in non-small cell lung cancer

In the last 6 years, since the first reports of an association between somatic mutations in epidermal growth factor receptor (EGFR) exons 19 and 21 and response to EGFR tyrosine kinase inhibitors (TKIs), treatment of non-small cell lung cancer (NSCLC) has changed dramatically. Based on laboratory and clinical observations, investigators have anticipated that these mutations could be predictive of response to EGFR TKIs and numerous studies have confirmed that the presence of mutation was associated with longer survival in patients receiving targeted therapy. Prospective trials comparing standard platinum-based chemotherapy with EGFR TKIs in patients with and without activating EGFR mutations validated the predictive value of molecular selection of patients for first-line treatment of advanced NSCLC. Recently, preclinical and first-in-human studies have demonstrated impressive activity of ALK TKI in tumors harboring ALK rearrangement. In this article, we review current data on molecular biology of lung cancer and evidence-based patient selection for targeted therapy.     

Pretreatment direct bilirubin and total cholesterol are significant predictors of overall survival in advanced non‐small‐cell lung cancer patients with EGFR mutations

This study was designed to examine the prediction of pretreatment circulating bilirubin and cholesterol for overall survival in 459 advanced non‐small‐cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Circulating total bilirubin, direct bilirubin (DB), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C) levels were measured at baseline. The mean age (standard deviation) of all study patients was 58.7 (10.5) years, and 42.9% of them was males. Ever smokers accounted for 27.0% and lung adenocarcinoma for 90.4%. The median follow‐up time and survival time were 29.5 and 34.9 months, respectively. Patients with higher DB had a 1.68‐fold increased risk of death compared with patients with lower DB (hazard ratio [HR] = 1.68, 95% confidence interval [CI]: 1.22–2.30, p = 0.001), while patients with higher TC were at a 63% reduced risk of death compared with patients with lower TC (HR = 0.37, 95% CI: 0.20–0.67, p = 0.001). As for HDL‐C, patients with higher levels had the risk of death reduced by 46% (HR = 0.54, 95% CI: 0.29–1.00, p = 0.049) compared with patients with lower levels. After the Bonferroni correction, only DB and TC were significantly associated with NSCLC survival. Our findings demonstrate for the first time that pretreatment DB was identified as a significant risk factor, yet TC as a protective factor, for overall survival in NSCLC patients with EGFR mutations.     

盐酸埃克替尼治疗晚期非小细胞肺癌的临床观察

目的:观察盐酸埃克替尼治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）的疗效、安全性及其影响因素。方法:回顾性分析云南省肿瘤医院2013年11月-2016年2月收治的接受盐酸埃克替尼治疗的晚期NSCLC患者56例,对患者疗效、生存期及毒副反应进行评价。结果:56例患者均可评价疗效,客观有效率（objective response rate,ORR）为30.4%,疾病控制率（disease control rate,DCR）为83.9%,中位无进展生存期（progression free survival,PFS）为9个月。腺癌患者的DCR、PFS均优于鳞癌患者（P＜0.05）。12例患者进行EGFR基因检测,均为突变阳性,EGFR突变患者的ORR为58.3%,DCR为100%,PFS为9个月。EGFR突变患者的ORR优于EGFR状态未知患者（P＜0.05）。毒副反应主要为轻度的皮肤毒性和腹泻。结论:盐酸埃克替尼是治疗晚期NSCLC的有效药物,毒副反应较轻,腺癌患者能获得较好的疗效,EGFR突变患者的疗效更好。     

Osimertinib in Japanese patients with EGFR T790M mutation‐positive advanced non‐small‐cell lung cancer: AURA3 trial

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first‐line treatment for patients with EGFR mutant non‐small‐cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third‐generation EGFR‐TKI that can inhibit the kinase even when the common resistance‐conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first‐line EGFR‐TKI treatment. AURA3 was a randomized (2:1), open‐label, phase III study comparing the efficacy of osimertinib (80 mg/d) with platinum‐based therapy plus pemetrexed (500 mg/m²) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first‐line EGFR‐TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary end‐point was progression‐free survival (PFS) based on investigator assessment. Improvement in PFS was clinically meaningful in the osimertinib group (n = 41) vs the platinum‐pemetrexed group (n = 22; hazard ratio 0.27; 95% confidence interval, 0.13‐0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum‐pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in 5 patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum‐pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR T790M mutation‐positive NSCLC whose disease has progressed following first‐line EGFR‐TKI treatment. (ClinicalTrials.gov trial registration no. NCT02151981.)     

Second‐Line Therapy for Advanced NSCLC

Most patients with lung cancer have non‐small cell lung cancer (NSCLC) subtype and have advanced disease at the time of diagnosis. Improvements in both first‐line and subsequent therapies are allowing longer survival and enhanced quality of life for these patients. The median overall survival observed in many second‐line trials is approximately 9 months, and many patients receive further therapy after second‐line therapy. The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib are standard second‐line therapies. For patients with EGFR mutation, a TKI is the favored second‐line therapy if not already used in first‐line therapy. For patients without the EGFR mutation, TKIs are an option, but many oncologists favor cytotoxic therapy. The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second‐line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.     

Cost analysis of lung cancer management in South Western Sydney

Introduction: Lung cancer is the leading cause of cancer mortality in Western nations, and associated health‐care costs are escalating. The aim of this study was to describe the current pattern of resource use and direct medical costs associated in managing lung cancer in South Western Sydney, Australia. Methods: All new cases of primary lung carcinoma discussed at the Liverpool and Macarthur Cancer Therapy Centre (CTC) Lung Cancer Multidisciplinary Team meeting or seen at CTC between 1 December 2005 and 21 December 2006 were reviewed. Staging investigations, hospitalisation, treatment and follow‐up investigations were documented from first consultation to last follow‐up (31 October 2008 or death). Cost estimates were based on the Australian Medicare Benefits Schedule and reported in Australian dollars. Infrastructure, staff and non‐medical costs were excluded. Results: There were 210 patients, median age 68.2 years (range 39–90) with median follow‐up of 16.6 months. The pathology and stage distribution were: 3.8% limited stage small cell lung cancer (SCLC), 10.0% extensive stage SCLC, 13.4% stage I and II non‐small cell lung cancer (NSCLC), 28.5% stage III NSCLC and 44.3% stage IV NSCLC. The estimated total cost for managing this patient cohort was A$2.91 million. The cost components were: staging investigations (10.1%), treatment 41.2% (2.8% surgery, 15.8% radiotherapy and 22.6% chemotherapy), hospitalisation (43.7%) and follow‐up investigations (5%). The median costs for managing NSCLC and SCLC subgroups were A$10 675 (range A$669–612 789) and A$14 799 (range A$908–31 057), respectively. Conclusion: Hospitalisation and cancer treatment, particularly chemotherapy, accounted for the major components of direct medical costs in the management of lung cancer.     

Efficacy and safety of nivolumab in Japanese patients with advanced or recurrent squamous non‐small cell lung cancer

Limited treatment options are available for stage IIIB/IV non‐small cell lung cancer (NSCLC). Nivolumab, a programmed cell death‐1 immune checkpoint inhibitor antibody, has been shown to be effective for the treatment of NSCLC. The present study investigated the effectiveness and safety of nivolumab in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum‐containing chemotherapy. In this multicenter phase II study, patients were treated with nivolumab (3 mg/kg, i.v.) every 2 weeks until progressive disease or unacceptable toxicity was seen. Primary endpoint was overall response rate (ORR) assessed by independent radiology review committee (IRC) and secondary endpoints included a study site‐assessed ORR, overall survival (OS), progression‐free survival (PFS), duration of response, time to response, best overall response (BOR), and safety. The study included 35 patients from 17 sites in Japan. Patients had IRC‐assessed ORR of 25.7% (95% CI 14.2, 42.1) and the study site‐assessed ORR was 20.0% (95% CI 10.0, 35.9). Median OS, median time to response and median PFS were 16.3 (95% CI 12.4–25.4), 2.7 (range 1.2–5.5) and 4.2 (95% CI 1.4–7.1) months, respectively. The IRC‐assessed BOR was partial response, stable disease, and progressive disease for 25.7%, 28.6%, and 45.7% of patients, respectively. Treatment‐related adverse events were reported in 24 patients (68.6%), most of which resolved with appropriate treatment including steroid therapy or ?discontinuation of nivolumab. Nivolumab was effective and well tolerated in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum‐containing chemotherapy. Clinical trial registration number: JapicCTI‐132072