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Purpose Alectinib is an anaplastic lymphoma kinase (ALK) –specific kinase inhibitor that seems to be effective against non–small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor–naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.

9022 Background: The primary analysis of the J-ALEX (JapicCTI-132316) study for the ALK-inhibitor naïve ALK+ NSCLC demonstrated superior progression-free survival (PFS) in Japanese patients randomized to the ALC, compared with those assigned in the CRZ (HR 0.34, 99.7% CI 0.17–0.71, stratified log-rank p

8571 Background: Carboplatin and etoposide is the current standard treatment for elderly extensive-disease small-cell lung cancer (ED-SCLC). The purpose of this study is to evaluate the efficacy and safety of carboplatin and irinotecan compared with carboplatin and etoposide in elderly Japanese patients with ED-SCLC in a randomized phase II/III design. Methods: Eligibility included histologically or cytologically proven SCLC, no previous systemic chemotherapy, performance status of 0 to 2, and aged 71 years or older. Patients received carboplatin (AUC 5 mg/ml/min on day 1) and etoposide (80 mg/m2 on day 1 to 3) (CE) every 3 weeks for 4 cycles or carboplatin (AUC 4 mg/ml/min on day 1) and irinotecan (50 mg/m2 on day 1 and 8) (CI) every 3 weeks for 4 cycles. In the phase II part, the primary endpoint was the objective response rate of the CI arm and the secondary endpoint was adverse events. In the phase III part, the primary endpoint was overall survival, and the secondary endpoints were progression-free survival, objective response rate, adverse events, and symptom score. This study was designed to confirm the superiority of CI arm in terms of overall survival over CE arm. The median survival time with CI arm was expected to be increased by 3.5 months with hazard ratio (HR) of 0.750 (10.5 vs. 14.0 months). The sample size was set at 250 to observe the required number of events of 227 with one-sided alpha level of 0.05, a power of 70%, an accrual period of 6.5 years, and a follow-up period of 1.5 years. Results: Between December 2013 and June 2019, 258 patients were randomized (CE arm, 129 patients; CI arm, 129 patients). The median age was 75 (range, 71-90). The characteristics of the patients were well balanced between CE arm and CI arm. Overall survival, progression-free survival, and objective response rate of CE arm vs. CI arm were 12.0 (95% CI, 9.3-13.7) vs. 13.2 (95% CI, 11.1-14.6) months (HR, 0.848 (95% CI, 0.650-1.105)) (one-sided P=0.11), 4.4 (95% CI, 4.0-4.7) vs. 4.9 months (95% CI, 4.5-5.2) (HR, 0.851 (95% CI, 0.664-1.090)) (two-sided P=0.21), and 59.7% (77 of 129) vs. 64.3% (83 of 129), respectively. Symptom score showed no significant difference between the arms. Higher incidences of myelosuppression of grade 3 or worse occurred with CE arm, whereas higher incidences of gastrointestinal toxicity of grade 3 or worse occurred with CI arm. Three treatment-related deaths including lung infection in CE arm and lung infection and sepsis in CI arm were observed. Conclusions: Efficacy tended to be favorable in carboplatin and irinotecan arm, but there was no statistically significant difference. These results indicate that carboplatin and etoposide is a still standard treatment in elderly Japanese patients with ED-SCLC. Clinical trial information: 000012605.

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.

Purpose Phase I data (ASCEND-1) showed ceritinib efficacy in patients with ALK-rearranged non–small-cell lung cancer (NSCLC), regardless of brain metastases status and with or without prior therapy with an inhibitor of the ALK protein. Data are presented from a phase II trial (ASCEND-2) in which ceritinib efficacy and safety were evaluated in patients who had ALK-rearranged NSCLC previously treated with at least one platinum-based chemotherapy and who had experienced progression during crizotinib treatment as their last prior therapy. Patients and Methods Patients with advanced ALK-rearranged NSCLC, including those with asymptomatic or neurologically stable baseline brain metastases, received oral ceritinib 750 mg/d. Whole-body and intracranial responses were investigator assessed (according to RECIST version 1.1). Patient-reported outcomes were evaluated with the Lung Cancer Symptom Scale and European Organisation for Research and Treatment of Cancer surveys (the core-30 and the 13-item lung cancer–specific quality-of-life questionnaires). Results All 140 patients enrolled had received two or more previous treatment regimens, and all patients had received crizotinib. The median duration of exposure and the follow-up time with ceritinib were 8.8 months (range, 0.1 to 19.4 months) and 11.3 months (range, 0.1 to 18.9 months), respectively. Investigator-assessed overall response rate was 38.6% (95% CI, 30.5% to 47.2%). Secondary end points, all investigator assessed, included disease control rate (77.1%; 95% CI, 69.3% to 83.8%), time to response (median, 1.8 months; range, 1.6 to 5.6 months), duration of response (median, 9.7 months; 95% CI, 7.1 to 11.1 months), and progression-free survival (median, 5.7 months; 95% CI, 5.4 to 7.6 months). Of 100 patients with baseline brain metastases, 20 had active target lesions at baseline; investigator-assessed intracranial overall response rate was 45.0% (95% CI, 23.1% to 68.5%). The most common adverse events (majority, grade 1 or 2) for all treated patients were nausea (81.4%), diarrhea (80.0%), and vomiting (62.9%). Patient-reported outcomes showed a trend toward improved symptom burden. The global quality-of-life score was maintained during treatment. Conclusion Consistent with its activity in ASCEND-1, ceritinib treatment provided clinically meaningful and durable responses with manageable tolerability in chemotherapy- and crizotinib-pretreated patients, including those with brain metastases.

e21623 Background: IMpower110 evaluated atezo mono in PD-L1–selected, chemo-naive patients (pts) with nonsquamous (nsq) or squamous (sq) NSCLC. At the interim analysis, IMpower110 met its primary OS endpoint, with a statistically significant and clinically meaningful improvement for atezo vs chemo in TC3 or IC3 wild-type ( EGFR/ALK-negative) pts. We report on the safety profile of atezo vs chemo in IMpower110. Methods: 572 pts with stage IV nsq or sq NSCLC, PD-L1 expression ≥ 1% on TC or IC and ECOG PS 0-1 were randomized 1:1 to receive atezo (1200 mg IV q3w) or chemo (4 or 6 21-day cycles). In the chemo arm, nsq pts received cisplatin (cis) 75 mg/m2 or carboplatin (carbo) AUC 6 + pemetrexed (pem) 500 mg/m2 IV q3w; sq pts received cis 75 mg/m2 + gemcitabine (gem) 1250 mg/m2 or carbo AUC 5 + gem 1000 mg/m2 IV q3w. Safety was assessed in all treated pts (safety evaluable [SE] population [pop]), regardless of PD-L1 expression or EGFR/ALK status. AEs were summarized per MedDRA v22.0 and severity graded per NCI CTCAE v4.0. Immune-mediated AEs (imAEs) were defined per a sponsor-specified list of terms, regardless of whether the events led to systemic glucocorticoid, endocrine therapy, or other immunosuppressants use. Results: At data cutoff (Sep 10, 2018) within the ITT pop, treatment (tx) was ongoing in 90 (atezo: 31.6%) and 25 (chemo: 8.7%) pts, with 13.7 mo of follow-up. Within the SE pop (atezo: n = 286, chemo: n = 263), atezo pts had longer tx exposure (5.3 mo) vs chemo pts (pem, 3.5 mo; gem, 2.6 mo; carbo, 2.3 mo; cis, 2.1 mo). Atezo had a favorable safety profile vs chemo (table); safety data were consistent with data from a pooled atezo mono pop. imAEs occurred in 40.2% (atezo) and 16.7% (chemo) of pts and were Grade (Gr) 3-4 in 6.6% and 1.5%, respectively. Conclusions: Atezo was better tolerated than chemo and imAEs were generally low grade. Overall, the safety experience with atezo mono in IMpower110 was consistent with its known safety profile; no new safety signals were identified. Clinical trial information: NCT02409342. [Table: see text]

9537 Background: Brigatinib is an ALK inhibitor with demonstrated activity against ALK resistance mutations. To evaluate efficacy and safety in Japanese patients with ALK-positive non-small cell lung cancer (NSCLC), a prospective, single-arm, phase 2 study was conducted. We report the efficacy and safety of brigatinib in patients who have progressed on alectinib with or without prior crizotinib and of those who previously received up to two ALK tyrosine kinase inhibitors (TKIs) with or without prior chemotherapy. Methods: A safety evaluation lead-in was followed by an expansion stage of an ALK TKI-naïve and two ALK TKI-refractory cohorts. The refractory cohorts included patients with stage IIIB, IIIC, or IV NSCLC with ALK rearrangements. This report describes efficacy results from the post-alectinib patients in the expansion cohort and safety results from all refractory patients. The primary endpoint was confirmed objective response rate (ORR) assessed by IRC, secondary endpoints included duration of response (DoR), progression-free survival (PFS), disease control rate (DCR), and intracranial ORR (iORR). Brigatinib was administered at 180 mg QD with 90 mg QD lead-in for the first 7 days, and efficacy was evaluated every 8 weeks. Results: A total of 72 patients were enrolled in 28 sites, including a cohort of 47 patients with prior alectinib, with/without crizotinib between January 2018 and September 2019. The primary analysis of brigatinib in this cohort (data cut-off date 26 September 2019) demonstrated an IRC-assessed, confirmed ORR of 30% and a median DoR of 6.1 months. The median PFS was 7.3 months. Clinically meaningful intracranial efficacy was also observed (see table). Grade ≥3 TEAEs included blood creatine phosphokinase increase (18.1%), lipase increase (13.9%), hypertension (11.1%), amylase increase (4.2%), and pneumonitis (1.4%). Brigatinib also showed anti-tumor activity in patients with refractory secondary mutations in the ALK kinase domain, including G1202R, I1171N, V1180L, and L1196M. Conclusions: Brigatinib showed clinically meaningful efficacy in Japanese patients refractory to prior alectinib (first line or post crizotinib), regardless of prior chemotherapy. The safety profile of brigatinib was consistent with prior studies and no new safety findings were identified. Clinical trial information: NCT03410108 . [Table: see text]

9574 Background: Prior data from a phase I/II study showed durable responses, including efficacy in brain lesions, and a tolerable safety profile with nazartinib in treatment (tx)-naïve patients (pts) with EGFR-mutant (mut), locally advanced (adv)/metastatic NSCLC. Here we report updated phase II results, including overall survival (OS). Methods: Tx-naïve adult pts with activating EGFR-mut (L858R or ex19del), stage IIIB/IV adv NSCLC with neurologically stable and controlled brain metastasis (BM) received oral nazartinib 150 mg once daily (continuous schedule). Primary endpoint: overall response rate (ORR) by BIRC per RECIST v1.1; secondary endpoints: disease control rate (DCR), duration of response (DOR), time to response, progression-free survival (PFS), OS, and safety. Results: At data cut-off (Nov 1, 2019), 45 pts were enrolled (median [range] age: 64 [28–83] years; 26 pts [58%] ECOG PS 1; 18 pts [40%] had baseline BM). EGFR mutations: 56% ex19del, 40% L858R, 4% other. 26/45 pts (58%) discontinued tx, with the primary reason being progressive disease in 19 pts (42%); 2 pts (4%) discontinued tx due to AEs. Median (range) follow-up for OS: 25 (0–33) months (mo); and for PFS: 17 (0–33) mo. ORR by BIRC: 69%; median PFS by BIRC: 18 mo; median OS was NE and at 33 mo, 56% of pts were alive (Table). BIRC results by baseline BM are shown in the Table. Median (range) duration of exposure: 24 (0–34) mo. Most frequent AEs (≥20% all grade, all causality): diarrhea (47%), maculopapular rash (38%), pyrexia (29%), cough and stomatitis (27% each), decreased appetite and pruritus (24% each), and dermatitis acneiform (22%). Most frequent grade 3/4 AEs (≥10%, all causality): maculopapular rash (5 pts [11%]; all grade 3) and increased lipase (5 pts [11%]; 1 pt with grade 4; no clinical pancreatitis AE was observed). Conclusions: After additional follow-up, median OS was still not reached and the safety profile was manageable. Nazartinib is a promising 3rd generation EGFR TKI for tx-naïve pts with adv EGFR-mut NSCLC, including pts with baseline BM. Clinical trial information: NCT02108964 . [Table: see text]

9092 Background: The primary analysis of the J-ALEX (JapicCTI-132316) study for the ALK-inhibitor naïve ALK+ NSCLC demonstrated superior progression-free survival (PFS) of ALC compared with CRZ (HR 0.34, 99.7% CI 0.17–0.71, stratified log-rank p < 0·0001) by the Independent Review Facility (IRF) (data cutoff, December 3 2015, Hida et al., Lancet 2017) . Here, we report the final PFS and OS 2nd interim data (data cutoff, June 30 2018). Methods: ALK+ NSCLC (by IHC and FISH or RT-PCR) patients were randomized 1:1 either to receive ALC (300 mg BID, n = 103) or CRZ (250 mg BID, n = 104). Stratification factors included ECOG PS, treatment line, and clinical stage. Primary endpoint was PFS according to the blinded IRF. Secondary endpoints included OS, objective response rate, and safety. Results: After a median follow-up of 42.2 months in the ALC arm and 42.4 months in the CRZ arm, an event of disease progression or death occurred in 54% and 86% in the ALC arm and the CRZ arm, respectively. The final PFS HR was 0.37 (95%CI 0.26-0.52): median IRF-PFS was 34.1 months (95%CI 22.1– not estimated) in the ALC arm and 10.2 months (95%CI 8.3–12.0) in the CRZ arm. HRs for the time to CNS progression or death was 0.33 (95%CI 0.11–0.93) and 0.20 (95%CI 0.08–0.49) with or without CNS metastases at baseline, respectively. The 2nd interim analysis of OS was still immature (events 30.1% in the ALC arm, 31.7% in the CRZ arm; stratified HR 0.80, 95%CI 0.35–1.82). Most of patients (77.9%) in the CRZ arm received ALC as a subsequent therapy whereas only 10.7% of patients in the ALC arm received CRZ. Proportion of patients with grade 3–4 AEs (37% vs 61%), AEs leading to interruption (40% vs 82%) or discontinuation (12% vs 23%) were lower in the ALC arm than the CRZ arm. There were no treatment-related deaths in either arm. Conclusions: In the final PFS analysis, ALC continued to demonstrate the superiority in IRF-PFS in ALK-inhibitor naïve ALK+ NSCLC regardless of baseline CNS metastases with a favorable safety profile. The updated result of OS will be presented in the future congress. Clinical trial information: JapicCTI-132316.

9004 Background: Capmatinib is a highly potent and selective MET inhibitor. Previous data of GEOMETRY mono-1 study showed a clinically meaningful overall response rate (ORR) and manageable toxicity profile in patients (pts) with METΔex14–mutated NSCLC who received 1–2 prior lines of treatment (tx) (Cohort 4) and in particular a high ORR in tx-naïve pts (Cohort 5b). Here we report the results in METΔex14–mutated NSCLC for duration of response (DOR) and progression-free survival (PFS) as well as the updated results for ORR. Methods: GEOMETRY mono-1 is a phase 2, multi-cohort, multicenter study evaluating capmatinib in pts with METΔex14-mutated or MET-amplified advanced NSCLC across 6 cohorts. Pts (≥18 yrs) with ECOG PS 0–1, ALK and EGFR wt, and stage IIIB/IV NSCLC were eligible. Pts with METΔex14 mutation (centrally confirmed) were assigned (regardless of MET amplification status/gene copy number) to Cohorts 4 and 5b and received capmatinib tablets 400 mg BID. Primary endpoint was ORR by Blinded Independent Review Committee (BIRC) per RECIST v1.1. Key secondary endpoint was DOR by BIRC. Results: As of Nov 08, 2018, 97 pts with METΔex14-mutated NSCLC (Cohort 4: 69 pts; Cohort 5b: 28 pts) were evaluable for efficacy. ORR (95% CI) by BIRC was 39.1% (27.6-51.6) in Cohort 4 and 71.4% (51.3-86.8) in Cohort 5b. While still immature at the time of this analysis, data on durability are promising: median DOR (95% CI) by BIRC was 9.72 (4.27-11.14) and 8.41 (5.55-NE) mo for Cohorts 4 and 5b, respectively; median PFS (95% CI) by BIRC was 5.42 (4.17-6.97) and 9.13 (5.52-13.86) mo for Cohorts 4 and 5b, respectively. Safety profile remains favourable and unchanged. Most common AEs (≥25% all grades) across all cohorts (n = 315), were peripheral edema (49.2%), nausea (43.2%), and vomiting (28.3%); majority of the AEs were grade 1/2. Final efficacy analysis (12-mo f-u on DOR) including biomarker data will be presented during meeting. Conclusions: These data confirm capmatinib to be a promising new treatment option for pts with METΔex14-mutated advanced NSCLC regardless of the line of therapy with deep and durable responses and manageable toxicity profile. Clinical trial information: NCT02414139.

Purpose New molecular targeted agents are needed for patients with non–small-cell lung cancer (NSCLC) who progress while receiving erlotinib, gefitinib, or both. Afatinib, an oral irreversible ErbB family blocker, has preclinical activity in epidermal growth factor receptor (EGFR [ErbB1]) mutant models with EGFR-activating mutations, including T790M. Patients and Methods This was a Japanese single-arm phase II trial conducted in patients with stage IIIB to IV pulmonary adenocarcinoma who progressed after ≥ 12 weeks of prior erlotinib and/or gefitinib. Patients received afatinib 50 mg per day. The primary end point was objective response rate (complete response or partial response) by independent review. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results Of 62 treated patients, 45 (72.6%) were EGFR mutation positive in their primary tumor according to local and/or central laboratory analyses. Fifty-one patients (82.3%) fulfilled the criteria of acquired resistance to erlotinib and/or gefitinib. Of 61 evaluable patients, five (8.2%; 95% CI, 2.7% to 18.1%) had a confirmed objective response rate (partial response). Median PFS was 4.4 months (95% CI, 2.8 to 4.6 months), and median OS was 19.0 months (95% CI, 14.9 months to not achieved). Two patients had acquired T790M mutations: L858R + T790M, and deletion in exon 19 + T790M; they had stable disease for 9 months and 1 month, respectively. The most common afatinib-related adverse events (AEs) were diarrhea (100%) and rash/acne (91.9%). Treatment-related AEs leading to afatinib discontinuation were experienced by 18 patients (29%), of whom four also had progressive disease. Conclusion Afatinib demonstrated modest but noteworthy efficacy in patients with NSCLC who had received third- or fourth-line treatment and who progressed while receiving erlotinib and/or gefitinib, including those with acquired resistance to erlotinib, gefitinib, or both.

Purpose This phase III trial of concurrent thoracic radiotherapy (TRT) was conducted to compare third-generation chemotherapy with second-generation chemotherapy in patients with unresectable stage III non–small-cell lung cancer (NSCLC). Patients and Methods Eligible patients received the following treatments: A (control), four cycles of mitomycin (8 mg/m2 on day 1)/vindesine (3 mg/m2 on days 1, 8)/cisplatin (80 mg/m2 on day 1) plus TRT 60 Gy (treatment break for 1 week); B, weekly irinotecan (20 mg/m2)/carboplatin (area under the plasma concentration-time curve [AUC] 2) for 6 weeks plus TRT 60 Gy, followed by two courses of irinotecan (50 mg/m2 on days1, 8)/carboplatin (AUC 5 on day1); C, weekly paclitaxel (40 mg/m2)/carboplatin (AUC 2) for 6 weeks plus TRT 60 Gy, followed by two courses of paclitaxel (200 mg/m2 on day1)/carboplatin (AUC 5 on day 1). Results The median survival time and 5-year survival rates were 20.5, 19.8, and 22.0 months and 17.5%, 17.8%, and 19.8% in arms A, B, and C, respectively. Although no significant differences in overall survival were apparent among the treatment arms, noninferiority of the experimental arms was not achieved. The incidences of grade 3 to 4 neutropenia, febrile neutropenia, and gastrointestinal disorder were significantly higher in arm A than in arm B or C (P < .001). Chemotherapy interruptions were more common in arm B than in arm A or C. Conclusion Arm C was equally efficacious and exhibited a more favorable toxicity profile among three arms. Arm C should be considered a standard regimen in the management of locally advanced unresectable NSCLC.

9008Background: ALK tyrosine kinase inhibitors (TKIs) are standard of care for patients (pts) with advanced ALK+ NSCLC, and preclinical data suggest potential synergistic activity with checkpoint i...

9094Background: Nazartinib (EGF816) is a third-generation EGFR-TKI selective for activating and T790M mutations while sparing wild-type EGFR. In the Phase I part of a Phase I/II multicenter study o...

8530Background: S-1 is an oral anticancer agent containing a mixture of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, which has been shown to have a radiosensitizing effect in pr...

PurposeGefitinib is a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase. We conducted a phase III trial to evaluate whether gefitinib improves survival as sequential therapy after platinum-doublet chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC).Patients and MethodsChemotherapy-naïve patients with advanced stage (IIIB/IV) NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 1, and adequate organ function were randomly assigned to either platinum-doublet chemotherapy up to six cycles (arm A) or platinum-doublet chemotherapy for three cycles followed by gefitinib 250 mg orally once daily, until disease progression (arm B). Patients were stratified by disease stage, sex, histology, and chemotherapy regimens. The primary end point was overall survival; secondary end points included progression-free survival, tumor response, safety, and quality of life.ResultsBetween March 2003 and May 2005, 604 patients were randomly assigned. There was a statistically significant improvement in progression-free survival in arm B (hazard ratio [HR], 0.68; 95% CI, 0.57 to 0.80; P < .001); however, overall survival results did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.03; P = .11). In an exploratory subset analysis of overall survival by histologic group, patients in arm B with adenocarcinoma did significantly better than patients in arm A with adenocarcinoma (n = 467; HR, 0.79; 95% CI, 0.65 to 0.98; P = .03).ConclusionThis trial failed to meet the primary end point of OS in patients with NSCLC. The exploratory subset analyses demonstrate a possible survival prolongation for sequential therapy of gefitinib, especially for patients with adenocarcinoma.

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.

9064 Background: ALC is a highly selective, CNS-active ALK tyrosine kinase inhibitor. In the J-ALEX study, ALC proved superior efficacy and tolerability compared to CRZ at the pre-planned interim analysis at 83 progression free survival (PFS) events (51% of target events) . Here we report the updated data with a further 10 months of follow up. Methods: Patients with advanced ALK+ NSCLC were randomized 1:1 to receive ALC 300 mg b.i.d or CRZ 250 mg b.i.d and stratified by ECOG PS, treatment line, and clinical stage. Study Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was PFS according to the blinded independent review. Secondary endpoints included investigator-assessed PFS, overall survival, objective response rate and safety. Results: From Nov 2013 to Aug 2015, 207 patients were enrolled. Data cut off for the present analysis was Sep 2016. Median durations of PFS follow up were 20.5 months in the ALC arm and 20.4 months in the CRZ arm with 116 events by independent review observed. The updated PFS HR was 0.38 (95% CI: 0.26-0.55, p< 0.0001). Median PFS was 25.9 months (95% CI: 20.3-not estimated) with ALC and 10.2 months (95% CI: 8.3-12.0) with CRZ. For patients without brain metastasis at baseline (n = 164), ALC prevented CNS metastasis onset compared to CRZ (HR = 0.19, 95% CI: 0.07-0.53). For patients with brain metastasis at baseline (n = 43), ALC also prevented CNS progression compared to CRZ (HR = 0.51, 95% CI: 0.16-1.64). Adverse events (AEs) with frequency of more than 30% were constipation (37.9%) and nasopharyngitis (32.0%) in the ALC arm, while in the CRZ arm nausea (76.0%), diarrhea (74.0%), vomiting (57.7%), visual disturbance (54.8%), dysgeusia (51.9%), constipation (46.2%), increased ALT (32.7%), and increased AST (31.7%) were observed. Grade 3-4 AEs occurred with greater frequency in the CRZ arm (ALC: 32.0% vs CRZ: 56.7%). There were no Grade 5 AEs in either arm. Conclusions: In the updated analysis, ALC consistently showed superior efficacy compared to CRZ in systemic disease and prevention of CNS progression. ALC was also associated with a more favorable tolerability profile than CRZ. Clinical trial information: JapicCTI-132316.

9037 Background: EGFR-activating mutations (eg, exon 19 deletions [ex19del], L858R) occur in ~50% of East Asian patients with non-small cell lung cancer (NSCLC) and confer sensitivity to tyrosine kinase inhibitor (TKI) treatment. ASP8273, an orally administered EGFR TKI that inhibits EGFR-activating mutations, has demonstrated clinical activity in subjects with EGFR mutation-positive (EGFRmut+) NSCLC. Methods: EGFR TKI-naïve adult subjects (≥20 yr) with EGFRmut+ NSCLC were enrolled in this single arm Phase 2 study conducted in Japan (NCT02500927). Subjects received open-label ASP8273 300 mg once daily until discontinuation criteria were met. Primary endpoint was tolerability; secondary endpoint was antitumor activity defined by RECIST v1.1. Results: A total of 31 Japanese subjects (12 M/19 F; median age 64 years [range: 31–82]) were enrolled. Based on local testing, 27 subjects had an ex19del (n = 13, 42%) or a L858R (n = 14, 45%) EGFR activating mutation; 4 subjects (13%) had other EGFR activating mutations (L861Q [n = 2], G719X [n = 2]). ASP8273 300 mg had tolerable adverse events with diarrhea and peripheral neuropathy being most common; no interstitial lung disease events were reported (Table). Across all 31 subjects, based on investigator assessment, treatment with 300 mg ASP8273 was associated with an overall response rate (ORR) of 52%, disease control rate (DCR) of 94%, and a median duration of progression-free survival (PFS) of 11.3 months (95% CI: 7.2, 15.5). In subjects with ex19del, ASP8273 300 mg was associated with an ORR of 46% and DCR of 85%; median PFS was 8.3 months (95% CI: 2.9, -). In subjects with the L858R, ASP8273 300 mg was associated with an ORR of 57% and DCR of 100%; median PFS was 15.5 months (95% CI: 7.2, 15.5). Conclusions: Once-daily ASP8273 300 mg was tolerable in TKI-naïve Japanese subjects with EGFRmut+ NSCLC and demonstrated antitumor activity. Clinical trial information: NCT02500927. [Table: see text]

9008Background: ALC showed promising efficacy and tolerability in the phase I/II study (AF-001JP). Here, we conducted the randomized open-label phase III trial (J-ALEX study, JapicCTI-132316) to prove superior progression-free survival (PFS) of ALC to CRZ in ALK+ NSCLC patients (pts) without prior ALK inhibitor treatment. Methods: ALK+ NSCLC pts were randomized 1:1 either to receive ALC (300 mg b.i.d.) or CRZ (250 mg b.i.d.) and stratified by ECOG PS (0/1 vs 2), treatment line (1st vs 2nd), and clinical stage (IIIB/IV vs recurrence). Treatment on both arms was continued until disease progression or unacceptable toxicity. Primary endpoint was PFS according to the blinded independent review board. Secondary endpoints included overall survival, objective response rate, and safety. Under an assumption of expected hazard ratio (HR) of 0.643, 164 events were required to have 80% power with 2-sided alpha of 0.05. Three interim analyses (IA) for early stopping due to efficacy were planned after 33%, 50%, and 75% ...

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...

8059 Background: In the ASCEND-1 study ceritinib showed clinical activity in pts with ALK+ NSCLC, including in brain metastases (BM). ASCEND-2 (NCT01685060) evaluated efficacy and safety of ceritin...

3036 Background: Tecemotide is a MUC1 antigen-specific cancer immunotherapy. We report results from a phase I/II study of tecemotide in Japanese patients (pts) with no disease progression (PD) afte...

8027 Background: Nivolumab, a fully human IgG4, PD-1 immune-checkpoint inhibitor antibody, has shown durable clinical activity in phase I and II trials in several tumor types. Recently, a phase III...

8061 Background: Alectinib, a CNS-penetrant, selective ALK inhibitor with a novel scaffold, was granted approval in Japan 2014, since it showed good efficacy and tolerability in ALK+ NSCLC pts with...

7504 Background: ETOP and irinotecan are drugs known to exert promising activity in SCLC. A phase II study of weekly chemotherapy using a combination of CDDP, ETOP and irinotecan (PEI), which are k...

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 ...

8052 Background: Although driver mutations in EGFR gene are often associated with initial dramatic response to EGFR-TKI, those patients inevitably develop acquired resistance. It is suggested that ...

8005 Background: Despite the development of EGFR tyrosine kinase inhibitors, median progression-free survival (PFS) is only about 13 months in patients with EGFR mutation–positive NSCLC. However, r...

8103 Background: Alectinib, a potent highly selective ALK inhibitor, shows good efficacy and safety for crizotinib-naive and -resistant patients (pts) with ALK-rearranged non-small cell lung cancer (NSCLC). However, each dose required 8 capsules (caps). Thus, a higher strength formulation was developed. Methods: This 2-arm crossover study (JP28927) evaluated the bioequivalence of alectinib 300 mg b.i.d. with 20 and 40 mg caps vs. 150 mg caps at steady state in ALK-rearranged NSCLC pts. Primary objectives were to evaluate bioequivalence between drug formulations and food effect with 150 mg caps; secondary objectives were to evaluate efficacy and safety. Arm 1 of Cycle 1 (30 d) consisted of 300 mg b.i.d. with 20/40 mg caps for 10 d, 150 mg caps for the next 10 d, and 150 mg caps after meals for the last 10 d. The order was different in arm 2: 150 mg caps for 10 d, 20/40 mg caps for the next 10 d, and 150 mg caps after meals for the last 10 d. After Cycle 1, to evaluate bioequivalence, pts continued alectini...

8033 Background: Anaplastic lymphoma kinase (ALK) is a constitutively activated tyrosine kinase in a subset of NSCLC with ALK fusion gene derived from chromosomal rearrangement. Previously, CH5424802, a highly selective, second-generation ALK inhibitor, has demonstrated clinically meaningful antitumor activity and a favorable toxicity profile (ESMO 2012). Here we report the updated results of this study. Methods: Patients (Pts) with ALK-positive NSCLC and no prior ALK inhibitor therapy were treated with CH5424802 at 300 mg bid until progressive disease or intolerable toxicity to investigate the efficacy and safety. Results: As of the cut-off date of Dec. 14, 2012, 58 pts have been treated with CH5424802: median age 49.5 years, M/F 25/33, ECOG PS 0/1 26/32, never-smoker 60.3%, ≥2 prior chemotherapy regimens 62%. Among the 46 pts in phase II part of this study, the overall response rate was 93.5% (95% CI: 82.1%, 98.6%) with 2 CRs and 41 PRs. Tumor shrinkage by 30% (PR) was achieved quickly with 65% occurring within 3 weeks of treatment and 87% within 6 weeks. With a median follow-up period of 12.6 months, 47/58 pts (40/46 pts in phase II part) were still on study treatment, and the median treatment duration has passed 10.3 months. The major treatment-related AEs were dysgeusia (21/58, 36%), rash, AST increased, blood bilirubin increased (19/58, 33% each), constipation and blood creatinine increased (17/58, 29% each), mostly grade 1-2. The major treatment-related grade 3 AEs were neutrophil count decreased (4/58, 7%). No grade 4 or fatal AEs were observed. Treatment-related visual disorders, vomiting and nausea were rare and mild. Conclusions: In patients with ALK-positive NSCLC but naïve to any ALK inhibitor therapy, treatment with CH5424802 demonstrated generally mild toxicity and lead to high response rate of 93.5% and durable treatment beyond 10 months, expecting that treatment duration can be longer than that of crizotinib. CH5424802 is therefore a promising new ALK inhibitor for NSCLC. Clinical trial information: JapicCTI-101264.

8105 Background: PROFILE 1007 compared the efficacy and safety of crizotinib with that of standard-of-care chemotherapy in patients with ALK+ NSCLC. Although the study was not designed for formal assessment of patient outcomes on crizotinib vs. PEM or crizotinib vs. DOC, due to later interest, we performed retrospective efficacy and safety analyses of patient subgroups treated with crizotinib or each chemotherapy individually. Methods: Patients with stage IIIB/IV ALK+ NSCLC previously treated with 1 prior platinum-based regimen were randomized to receive crizotinib 250 mg PO BID or chemotherapy (PEM 500 mg/m2 or DOC 75 mg/m2, IV q3 wk). Patients with progressive disease on chemotherapy were offered crizotinib treatment in a separate study. In these subgroup analyses, PFS and ORR based on independent radiologic review, and safety were evaluated. Results: Of 347 patients randomized, 172 received crizotinib, 99 PEM, 72 DOC, and 4 no treatment. At data cutoff (Mar 2012), 85 crizotinib patients, 21 PEM patients, and 7 DOC patients were receiving treatment. Median treatment duration was longer in the crizotinib arm (7.1 mo) than in either the PEM (4.1 mo) or DOC (2.1 mo) treatment subgroups. Median PFS was significantly longer on crizotinib (7.7 mo) than on either PEM (4.2 mo; HR, 0.59; P=0.0004) or DOC (2.6 mo; HR, 0.30; P

7003 Background: IP is the standard treatment for ED-SCLC, however often cause severe diarrhea. AP have shown promising activity in SCLC with fewer diarrhea. We conducted a phase III trial comparing AP with IP. Methods: Eligibility criteria included patients (pts) with chemotherapy-naïve, ED-SCLC, aged 20 to 70, and ECOG PS 0-1. Pts were randomized to receive either IP or AP, balancing for site, sex, and PS. IP comprised administration of I (60 mg/m2) iv on days 1, 8, and 15, and P (60 mg/m2) iv on day1,every 4 weeks. AP comprised administration of A (40 mg/m2) iv on day 1-3, and P (60 mg/m2) iv on day1, every 3 weeks. The planned sample size was 141 pts in each arm with a one-sided alpha of 5% and power of 70% and a non-inferiority margin of hazard ratio (HR) as 1.31. The primary endpoint was overall survival (OS). The secondary endpoints were response rate (RR), progression-free survival (PFS), adverse events (AEs), and quality of life (QOL). We evaluated pts’ QOL twice: at the baseline and after completion of the second course. Results: 284 pts were randomized to IP (n=142) and AP (n=142). Median age was 63, 84% were male, and 56% had PS 0. When 191pts enrolled, more febrile neutropenia (FN) was observed in AP than anticipated, and the initial dose of A was decreased from 40 mg/m2 to 35 mg/m2. At the second interim analysis conducted after the completion of patient accrual, the median OS of AP (15.0 m) was much worse than that of IP (18.3 m) and the HR (1.41; 96.3% CI, 1.03-1.93) exceeds even the non-inferiority margin, so the Data and Safety Monitoring Committee recommended early publication of the results. Median PFS was 5.7 (IP) vs. 5.2 months (AP) (HR 1.43, 95% CI, 1.13-1.82). RR was 69.5% (IP) vs. 77.9% (AP) (p=0.14). AEs in IP and AP arm were Grade 4 neutropenia (22.5% vs. 78.6%), G3-4 FN (10.7% vs. 32.1%), and G3-4 diarrhea (7.1% vs.1.4%). Proportion of improvement in physical status of QOL was 37.1%(IP) vs. 31.7%(AP), (odds ratio 0.72; 95%CI, 0.43-1.22; P=0.227). Conclusions: AP showed more bone marrow suppression than expected although it caused less diarrhea. The non-inferiority of AP to IP was not demonstrated and IP remains the standard treatment for ED-SCLC.

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.

7028 Background: Four cycles of EP plus AHTRT is the standard treatment for LD-SCLC. IP demonstrated statistically significant overall survival (OS) improvement compared to EP for extensive-stage SCLC (JCOG9511; Noda, et al.NEJM, 2002). EP plus AHTRT followed by 3 cycles of IP is feasible with acceptable toxicities for LD-SCLC (Kubota, et al. CCR,2005). Methods: Eligibility criteria included patients with previously untreated LD-SCLC with measurable lesion, ECOG PS of 0-1, age: 20=2 on days 1-3 and cisplatin 80mg/m2 on day 1) plus AHTRT (1.5 Gy b.i.d. total 45 Gy/3 weeks). Patients who achieved CR, good PR, PR or SD with induction EP/AHTRT were randomized to receive either 3 cycles of consolidation EP or IP (irinotecan 60 mg/m2 and cisplatin 60 mg/m2 on days 1, 8, 15). Patients with CR or good PR after consolidation chemotherapy received prophylactic cranial irradiation. The primary endpoint is OS after the randomization. The planned sample size for randomization is 250 with a one-sided alpha of 2.5% and at least 70% power to detect a difference between gruops, 30% in EP versus 42.5% in IP group in 3-year survival. Results: From Sep 2002 to Sep 2006, 281 patients from 36 institutions were registered. After the induction EP/AHTRT, 258 patients were randomized to consolidation EP (n=129) or IP (n=129). Patient demographics were well balanced between the two groups. At the final analysis, the superiority of IP in OS was not demonstrated (hazard ratio of IP to EP, 1.085 [95%CI: 0.80-1.46]; one sided p=0.70, stratifield log-rank test). Grade 3/4 neutropenia (95%/78%), anemia (35%/39%), thrombocytopenia (21%/5%), neutropenic fever (17%/14%), diarrhea (2%/10%) were observed in EP and IP groups, respectively. Conclusions: EP plus AHTRT followed by 3 cycles of IP failed to demonstrate survival advantage over 4 cycles of EP plus AHTRT which still is the standard treatment for LD-SCLC. [Table: see text]

7524 Background: An unmet medical need exists in NSCLC pts after failure of E or G [reversible EGFR tyrosine kinase inhibitors (TKIs)], particularly in pts with T790M EGFR mutations, the most common mechanism of acquired resistance. Afatinib (A), an irreversible erbB family blocker, has preclinical activity against T790M. A was tested in this phase II study in pts enriched for acquired resistance to E or G. Methods: Pts in Japan with Stage IIIB/IV NSCLC (ECOG PS 0–1) who had progressed according to RECIST after 1–2 lines of chemotherapy and ≥12 wks of E or G received 50 mg A orally qd. The primary endpoint was objective tumor response. Results: Of 62 pts (F:48; M:14), 11.3%, 79% and 9.7% had received prior erlotinib, gefitinib or both, respectively. 65% of pts had achieved a prior response with E/G. Median duration between end of prior treatment with E/G and the start of A was 3 wks. 73% of pts were EGFR mutation-positive in their primary tumors. 82% of pts met the definition of acquired resistance to E/G...

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...

7586 Background: Amrubicin (AMR), a totally synthetic 9-aminoanthracycline and potent topoisomerase II inhibitor, is approved in Japan for the treatment of lung cancer. We investigate the recommend...

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 ...

8036^ Background: Two phase III trials (ECOG 4599 and BO17704) demonstrated that the addition of bevacizumab (Bev) to platinum-based regimens improved overall and/or progression-free survival (PFS) in patients (pts) with advanced non-squamous NSCLC (Sandler et al. NEJM 2006; Manegold et al. ESMO2008). However, no investigation with Bev has been conducted in Japanese NSCLC pts. Methods: This randomized, open-label phase II study compared a 3-weekly regimen of 15mg/kg of Bev plus carboplatin/paclitaxel (CP) versus CP alone. The primary endpoint was PFS; secondary endpoints included overall survival (OS), response rate (RR) and safety. Eligibility criteria: histologically or cytologically documented previously untreated advanced or recurrent non-squamous NSCLC; ECOG PS 0–1; no brain metastases. A size of 180 pts was planned to be randomized to: C AUC=6 and P 200mg/m2 q3 wks for up to 6 cycles plus Bev continued to progression at 15mg/kg q3 wks, or CP alone at the randomization ratio of 2:1. The study was designed to observe a 20% reduction in the risk of a PFS event in the Bev arm compared with control. Results: Between 4/07 and 3/08, 180 pts were accrued. Three pts of them were ineligible and 3 pts were not dosed at all. PFS (as assessed by investigators) and RR were significantly improved. OS is immature due to short duration of follow up. Updated PFS results as assessed by the central review committee and OS data will be provided. No new safety signals for Bev were detected. Conclusions: This is the first study of Bev in Japanese pts with NSCLC. The addition of 15mg/kg of Bev to CP significantly improved PFS and RR. The HR of PFS seemed at least as good as previous trials outside Japan. Safety of Bev was within a range already reported. This study confirms the efficacy and safety of Bev in Japanese pts with NSCLC. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

LBA8012 Background: Gefitinib is a small molecule inhibitor of the EGFR tyrosine kinase. When combined with chemotherapy, no survival gain was observed compared to chemotherapy alone (INTACT I and ...

8101 Background: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with the therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients (pts) with advanced non-small cell lung cancer (NSCLC). Several phase II trials of EGFR-TKIs in pts positive for such EGFR mutations have yielded a high response rate and good survival; however, the number of pts enrolled onto those trials was too small to draw any firm conclusion. Methods: We carried out a combined analysis of seven prospective trials conducted in Japan examining the efficacy and safety of gefitinib monotherapy for advanced NSCLC pts with EGFR mutations. In the present study we updated OS and PFS data for the combined survival analysis and examined prognostic factors for OS and PFS using a Cox regression model. Tumor response and gefitinib-related adverse events were also analyzed using the combined data set. Results: A total of 148 pts were combined from the seven trials. The mean age was 64 years (...

7530 Background: Concurrent chemoradiotherapy plays an important role in the treatment of unresectable stage III NSCLC. Our group demonstrated a superiority of MVP with concurrent TRT over that with sequential TRT (Furuse, JCO, 1999), while weekly chemotherapy with concurrent TRT has acceptable toxicities and expected efficacy. We conducted a randomized phase III trial to compare the efficacy and toxicity of weekly chemotherapy with concurrent TRT against MVP by a non-inferiority design. Methods: Patients were assigned to 3 regimens; MVP: cisplatin (80 mg/m2 on days 1, 29), vindesine (3 mg/m2 on days 1, 8, 29, 36) and mitomycin (8 mg/m2 on days 1, 29) with concurrent TRT (60 Gy). After then, pts received 2 courses of consolidation chemotherapy with MVP; IC: weekly irinotecan (20 mg/m2) / carboplatin(AUC 2) for 6 weeks and TRT (60 Gy) followed by 2 courses of irinotecan(50 mg/m2) / carboplatin(AUC 5); PC: weekly paclitaxel (40 mg/m2)/carboplatin (AUC 2) and TRT (60 Gy) followed by 2 courses of paclitaxel (200 mg/m2) / carboplatin (AUC 5). Primary endpoint was overall survival. Results: From Sep 2001 to Sep 2005, 456 pts were randomized; 429 pts had evaluated responses. Pretreatment characteristics were well-balanced between 3 arms (median age 63 years (30–74), PS0/1 41/55%, Ad/Sq/others 43/45/12%). The achievement rates of full treatment in MVP, IC and PC were 39.9, 29.7, and 49.3 %; those of full-dose TRT/2 courses of consolidation chemotherapy were 81.1/41.3%, 41.4/29.7% and 59.7/50.0%, respectively. Major toxicities were as follows; G4 neutropenia in MVP, IC, PC were 76.9, 13.1, 4.2% (p No significant financial relationships to disclose.