Search

Purpose Anaplastic lymphoma kinase (ALK) rearrangement–positive non–small-cell lung cancers can be effectively treated with an ALK tyrosine kinase inhibitor (TKI) such as crizotinib, but the response magnitude and duration are heterogeneous. Several ALK variants have been identified, but few studies have focused on the effects of different ALK variants on the efficacy of crizotinib. Patients and Methods Among 55 patients treated with crizotinib as the initial ALK-TKI between January 2007 and December 2014, we identified 35 patients with tumor specimens that could be evaluated for ALK variants by reverse transcription polymerase chain reaction. We retrospectively evaluated the efficacy of crizotinib on the basis of the objective response rate and progression-free survival (PFS) according to the ALK variants. Results The most frequent ALK variant was variant 1 in 19 patients (54%), followed by variant 2 in five patients (14%), variant 3a/3b in four patients (12%), and other variants in seven patients (20%). Objective response rate was 69% in all patients, whereas it was 74% and 63% in the variant 1 and non–variant 1 groups, respectively. The median PFS time was significantly longer in patients with variant 1 than in those with non–variant 1 (median PFS, 11.0 months [95% CI, 6.5 to 43.0 months] v 4.2 months [95% CI, 1.6 to 10.2 months], respectively; P < .05). Multivariable analysis identified two significant factors associated with PFS duration, ALK variant 1 (hazard ratio, 0.350; 95% CI, 0.128 to 0.929; P < .05) and advanced stage (hazard ratio, 4.646; 95% CI, 1.381 to 21.750; P < .05). Conclusion Our results indicate the better efficacy of crizotinib in patients with ALK variant 1 versus non–variant 1. The ALK variant status might affect the efficacy of ALK-TKIs.

9524 Background: At present, platinum-doublet chemotherapy or in combination with an immune check point inhibitor are standard treatment for patients with metastatic or recurrent NSCLC which lacks somatic gene alterations. Although CbP is one of the commonly used treatment options for NS-NSCLC, its clinical utility is limited due to lack of optimal biomarkers. Methods: Chemotherapy-naïve patients with pathologically proven advanced or recurrent NS-NSCLC received carboplatin (area under the curve = 5-6, at investigator’s discretion) plus pemetrexed (500 mg/m2) every 3 weeks followed by maintenance pemetrexed until disease progression. Blood samples were collected before treatment for proteomic analysis using mass spectrometry (MS). A classifier was constructed based on both an objective response assessed by radiologist independent of attending physicians in accordance with RECIST v1.1 and expression profiles of protein in a training cohort. The constructed classifier was then assessed with a validation cohort evaluating prediction accuracy of good responder, progression free survival (PFS) and overall survival (OS). Results: Of 244 patients with NS-NSCLC in a training cohort, proteomic profiles in blood from 96 patients who responded or progressed after treatment with CbP were analyzed to develop a classifier based on weighted voting. Details of the classifier will be presented at the 2020 ASCO Annual Meeting. The classifier was then applied to validation cohort (n = 94), and we successfully identified patients who benefit from the treatment (55 in good MS group) or not (39 in poor MS group). The objective response rate of the good MS group was significantly higher than that of the poor MS group (30.9% vs. 5.1%; p = 0.0018). The good MS group showed a significantly improved survival compared to the poor MS group (median PFS, 6.0 m vs. 2.3 m; hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.09-0.27; p < 0.001; median OS, 25.7 m vs. 5.1 m; HR, 0.18; 95% CI, 0.1-0.34; p < 0.001). Conclusions: In the present study, we successfully developed and validated a predictive classifier using proteomic analyses with blood samples collected from patients before treatment with CbP, suggesting the clinical utility of the classifier in selecting NS-NSCLC patients for treatment with CbP. Clinical trial information: UMIN000008476 .

Purpose To evaluate the relationship between mutations of the epidermal growth factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection. Patients and Methods We sequenced exons 18-21 of the EGFR gene using total RNA extracted from 59 patients with lung cancer who were treated with gefitinib for recurrent lung cancer. Gefitinib effectiveness was evaluated by both imaging studies and change in serum carcinoembryonic antigen (CEA) levels. Results EGFR mutations were found in 33 patients (56%). Of these mutations, 17 were deletions around codons 746-750 and 15 were point mutations (12 at codon 858, three at other codons), and one was an insertion. EGFR mutations were significantly more prevalent in females, adenocarcinoma, and never-smokers. Gefitinib treatment resulted in tumor shrinkage and/or CEA decrease to less than half of the baseline level in 26 patients, tumor growth and/or CEA elevation in 24 patients, and gefitinib effect was not assessable in nine patients. Female, never-smoking patients with adenocarcinoma tended to respond better to gefitinib treatment. Gefitinib was effective in 24 of 29 patients with EGFR mutations, compared with two of 21 patients without mutations (P < .0001). Of note, del746-750 might be superior to L858R mutations for prediction of gefitinib response. Patients with EGFR mutations survived for a longer period than those without the mutations after initiation of gefitinib treatment (P = .0053). Conclusion EGFR mutations were a good predictor of clinical benefit of gefitinib in this setting.

9048Background: The resistance mechanism after EGFR-TKI failure is reportedly EGFR T790M secondary mutation in about half of EGFR-mutant NSCLC. However, the predictive marker for T790M mutation rem...

e20038Background: Whether fluorine 18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) metrics predict the clinical outcome in locally advanced non-small cel...

e19138 Background: The next generation ALK inhibitor, alectinib, reportedly has potent efficacy after crizotinib failure in ALK-positive NSCLC patients. In the present study, we investigated progre...

e19123 Background: Patients with NSCLC with EGFR-activating mutations initially respond to EGFR-TKIs. However, clinical efficacy is limited by acquired resistance, and the secondary EGFR T790M muta...

7558 Background: Concurrent chemoradiation therapy (CRT) is the current standard of care for patients with locally advanced lung adenocarcinoma, however little has been reported about the impact of EGFR mutation to CRT efficacy. Methods: From 2005-2012, we retrospectively screened 73 unresectable stage III adenocarcinoma patients who were examined EGFR mutation status and received definitive concurrent CRT consisting of platinum doublet in first-line setting, and compared the clinical outcomes and recurrence patterns according to mutation status. Results: Among 73 patients, EGFR mutation was detected in 21 (28.8%). Overall response rate did not differ between EGFR-mutant and wild-type patients (66.7% vs. 74.0%, p=0.362). Median recurrence-free survival (RFS) in concurrent CRT was significantly shorter in EGFR-mutated patients than wild-type patients (8.7 [95%CI: 6.7-10.8] vs. 13.5 [95%CI: 11.0-18.3] months, p=0.022). The 2 year recurrence-free survival rate was 5.6% and 23.8% in EGFR-mutant and wild-type ...

e18145 Background: Lung cancers that harbor EML4-ALK can be effectively treated with anaplastic lymphoma kinase (ALK) inhibitors. Recent reports showed that pemetrexed-based therapy might be an effective treatment in patients with ALK-positive NSCLC. However, the efficacy of other regimens is still not known. The purpose of this study is to investigate the clinical characteristics, the efficacy of the cytotoxic chemotherapy in the first and second line setting in EML4-ALK positive NSCLC with advanced stage. Methods: EML4-ALK fusion was screened with RT-PCR and immunohistochemistry. When positive results were obtained with either method, gene rearrangement of ALK was confirmed with fluorescent in-situ hybridization. The clinical efficacy of chemotherapy was evaluated retrospectively. Results: We evaluated 20 EML4-ALK positive patients with advanced stage. Twelve patients were without a history of smoking, and 6 light smokers and 2 smokers. Seventeen (85%) of 20 had stage IV disease. Nine cases were male, and 11 were female. The mean age was 46.3 years (range, 26-79 years). Most of the CT findings at the primary site were masses or nodules, while two cases showed air-space consolidation. In the first line chemotherapy, most of the treatment regimens included carboplatin or cisplatin in combination with one or more therapeutic agents, such as taxans, bevacizumab except one case who was treated only by S-1. In 13 cases which were evaluable, 7/13 (53.8%) had a PR, 4/13 (30.8%) had SD, and 2/13 (15.4%) had PD. The treatment regimens in the second line setting included one therapeutic agent such as docetaxel, pemetrexed, S-1 or an oral ALK inhibitor. Among 10 evaluable cases in the second line setting, 2/10 (20%) had a PR, 5/10 (50%) had SD, and 3/10 (30%) had PD. Two patients who had a PR were all treated by oral ALK inhibitor. Within 7 patients who were treated by cytotoxic agents, none had clinical response. Conclusions: Our study suggests that EML4-ALK positive patients may show relatively favorable response to cytotoxic drug in the first line setting, but low response in the second line setting. These data might be helpful for further clinical trials including EML4-ALK positive patients.

e17510 Background: Gefitinib has shown good activity in lung cancer harboring mutations in the epidermal growth factor receptor (EGFR) gene. However, how to integrate gefitinib into concurrent chemoradiotherapy for unresectable locally advanced non-small cell lung cancer (NSCLC) with EGFR mutations is uncertain. Methods: We present three cases of locally advanced lung adenocarcinoma with EGFR mutation, which were treated with gefitinib followed by weekly paclitaxel and carboplatin concurrent with radiation. Three female patients (median age, 73 years; range, 61–77 years) received induction gefitinib 150 mg daily for 1-2 months followed by weekly paclitaxel 40 mg/m2 weekly over 1 hour; carboplatin at AUC (area under the curve) of 2 weekly over 1 hour; and radiation therapy of 60 Gy in 30 fractions. Results: Gefitinib induced very rapid response within the first month without pulmonary toxicity. Subsequent concurrent chemoradiotherapy was performed with safety. One patient recurred as hematogenous lung metastases at 5 months after treatment. The remaining two patients are well doing without adverse events. Conclusions: The very quick response to induction gefitinib and sequential chemoradiotherapy may be an effective treatment with good tolerance. We believe that this treatment strategy deserves further evaluation in unresectable locally advanced NSCLC with EGFR mutations.

e13106 Background: Vadimezan (ASA404; 5,6-dimethylxanthenone-4-acetic acid), is a novel tumor vascular disrupting agent. It induces apoptosis of tumor vascular endothelial cells and production of c...

e17532 Background: Prophylactic cranial irradiation (PCI) can improve both disease- free and overall survival in selected patients with small cell lung cancer (SCLC). Although PCI in early LS-SCLC ...