bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of anti-transforming growth factor-beta (TGFß) monoclonal antibody GC1008 in relapsed malignant pleural mesothelioma (MPM).
Authors: Stevenson James , Kindler Hedy Lee , Schwed Daniel , Ranganathan Anjana , Jacobs-Small Mona , Shouldis Jennfier , Marshall Amy , Heitjan Daniel , Langer Corey J. , Hsu Frank James , Albelda Steven 
Published: March 2020

7077 Background: TGFβ is a pleiotropic cytokine overexpressed by MPM. Based on preclinical data documenting a key role for TGFβ in promoting growth and progression of MPM, we are conducting a phase II trial of GC1008 in patients (pts) with progressive MPM. Methods: Pts with progressive MPM by modified RECIST criteria and PS 0-1 with 1-2 prior systemic therapies (at least 1 pemetrexed-based) are eligible. Treatment plan: GC1008 3mg/kg IV over 90 minutes every 21 days. Responses are assessed by modified RECIST every 6 weeks. The primary endpoint is progression-free survival (PFS) rate at 3 months; secondary objectives include safety with GC1008, response rate by modified RECIST, time to progression (TTP), and overall survival (OS). Results: The modified Gehan stage 1 stopping criterion of 1/13 pts with 3 month PFS has been exceeded. To date, 13 pts (10 PS 0; 3 PS 1) with MPM (median age 69; 2F, 11M; 11 epithelial, 1 sarcomatoid, 1 biphasic) enrolled. Treatment-related toxicities include G1/2 fatigue (3 pts), nausea (1 pt) and xerosis (1 pt). Other adverse events possibly related to GC1008 were rapid disease progression in 1 pt after 2 cycles, and G2 skin keratoacanthoma in 1 pt after 5 cycles. Three pts met the primary objective of 3 month PFS at 4.1, 4.2 and 9 months each. Stable disease (SD) was seen in 3 pts (23%). Median TTP is 1.4 months (95% CI 1.2-∞); median OS is 13 months (95% CI 6-∞). Increased serum mesothelin levels have closely tracked disease progression. Serum from 6/13 pts showed new antibodies against MPM tumor lysates as measured by immunoblotting. Two of 3 pts with SD had anti-tumor antibody responses. Mean baseline plasma level of TGFβ was 2447 pg/ml but did not correlate with baseline plasma TGFβ or TTP. Conclusions: GC1008 was well tolerated in pretreated MPM patients. SD occurred in 3 pts, all with prior disease progression. Evidence for humoral anti-tumor immunity was seen in nearly half of enrollees and in 2 of 3 pts with SD. OS compares favorably to prior single-agent studies in pretreated MPM.
Elevated PDGFRB gene copy number gain as prognostic in resected malignant pleural mesothelioma.
Authors: Tsao Anne S. , Harun Nusrat , Fujimoto Junya , Devito Vikki , Lee J. Jack , Mehran Reza J. , Hong Waun Ki , Suraokar Milind B. , Wistuba Ignacio I. 
Published: March 2020

7078 Background: PDGF/PDGFR pathway has been implicated in malignant pleural mesothelioma (MPM) carcinogenesis. We sought to evaluate the incidence of PDGFRB gene copy number gain (CNG) and PDGFR pathway protein expression by immunohistochemistry (IHC) in the tumor cell cytoplasm, membrane, nucleus, and stroma, and correlate it to patient clinical outcome. Methods: 88 archived tumor blocks from resected MPM with full clinical information were used to perform the analyses. IHC biomarkers for PDGFRα,β and p-PDGFRβ, and fluorescence in situ hybridization were performed for analysis of PDGFRB gene CNG. Spearman’s rank correlation, Wilcoxon rank-sum test or Kruskal-Wallis test, BLiP plots, and Kaplan-Meier method were used to assess the biomarkers and their correlation to clinical outcome. Results: There were several correlations identified between the IHC biomarkers; however, none associated with patient demographics or histology subtype, with the exception of high cytoplasmic PDGFRα occurring in patients with no prior known asbestos exposure (p=0.029). In the CNG analysis, PDGFRB gene CNG in > 10% of tumor cells had lower cytoplasmic p-PDGFRβ (p=0.029), while PDGFRB gene CNG in > 40% of tumor cells had a higher cytoplasmic PDGFRβ (p=0.04). PDGFRB gene CNG status did not associate with patient demographics or tumor characteristics. Patients with PDGFRB CNG > 40% of tumor cells had an improved relapse-free survival (RFS) [HR 0.25 (95% CI 0.09, 0.72), p=0.0096]. In the patients with PDGFRB CNG > 40% of cells, the addition of chemotherapy appeared to also improve RFS (p=0.017). In the multi-covariate analyses for RFS, there was no association with any IHC biomarker. In the overall survival (OS) analysis, having PDGFRB gene CNG > 40% of tumor cells correlated with an improved OS [HR 0.32 (95% CI 0.11, 0.89), p=0.029] and the addition of peri-operative chemotherapy led to a trend towards improved OS (p=0.089). Conclusions: PDGFRB CNG > 40% of tumor cells is a potential prognostic biomarker in surgically resected MPM tumors. Adding chemotherapy to patients with PDGFRB CNG > 40% of cells improved RFS and led to a trend towards improved OS. Future validation of this biomarker in prospective trials is needed.
SWOG 0722: A phase II study of mTOR inhibitor everolimus (RAD001) in malignant pleural mesothelioma (MPM).
Authors: Garland Linda L. , Ou Sai-Hong , Moon James , Mack Philip C , Testa Joseph , Tsao Anne S. , Wozniak Antoinette J. , Gandara David R. 
Published: March 2020

7083 Background: MPM preclinical studies demonstrate activation of AKT pathway proteins, including mTOR, and provide the rationale to test everolimus, an mTOR inhibitor, in MPM. Methods: Unresectable MPM patients (pts) after 1-2 systemic regimens (including a platinum-based regimen), with PS 0-1, measurable disease and adequate organ function were treated with daily oral everolimus 10 mg. Study endpoints were progression-free survival (PFS) at 4 months, response rate,overall survival (OS), and frequency/severity of toxicities. Results: 61 pts were registered between 12/2008 and 9/2011; there were 57 evaluable pts for the primary endpoint of 4-month PFS. Median age was 65.9 yrs; M/F 43/14; prior regimens (1/2: 58%/42%); PS 0/1 (21%/79%); epithelial subtype 61%; biphasic 7%; NOS 28%; pending 4%. 5 pts remain on treatment. Preliminary data for 35 of 57 pts are as follows: RR 0% by standard RECIST and DCR of 14/35 (40%); data by mod RECIST are not yet available. Estimated 4-month PFS was 34% with an estimated median PFS of 3 months. The null hypothesis of 4-month PFS = 30% could not be rejected (p=0.28). 41 pts have died; median OS is estimated at 5 months. Frequent grade 1-3 toxicities were fatigue (55.4%), hypertriglyceridemia (41.1%), anemia (39.3%), nausea (33.9%), oral mucositis (32.1%), anorexia (32.1%), diarrhea (26.8%), and hyperglycemia (26.8%). One pt each had grade 4 and grade 5 dyspnea. Conclusions: The trial did not achieve the primary endpoint of an improvement of PFS at 4 months from 30% to 50%. Inhibition of mTOR using single agent everolimus is not active in unselected MPM patients. Other strategies for targeting the activated AKT pathway in MPM remain of interest.
A phase II study of second-line bendamustine in relapsed or refractory small cell lung cancer (SCLC).
Authors: Lovly Christine Marie , Li Chung-I , Hutchison Anne Smith , Carbone David Paul , Johnson David H. , Keedy Vicki Leigh , Pao William , Sandler Alan , Horn Leora 
Published: March 2020

7094 Background: Bendamustine is an alkylating agent with a nitrogen mustard group and purine-like benzimidazole group. Bendamustine in combination with carboplatin has shown efficacy as first line therapy in extensive stage SCLC with RR 73%, TTP 5.2 months and OS 8.3 months [Köster, et al, JCO 2007]. This study aims to investigate the efficacy and safety of single agent bendamustine as 2nd or 3rd line therapy in patients with extensive-stage disease, small-cell lung cancer (ED-SCLC). Methods: This is an open-label, single-arm, multicenter phase II trial. Eligible patients had previously treated ED-SCLC, up to 2 prior regimens, ECOG performance status 0-2, evaluable/measurable disease, and adequate marrow, renal and hepatic function. Patients with stable treated brain metastases were allowed. Patients were treated with bendamustine (120mg/m2 IV days 1 and 2 every 3 weeks) for up to 6 cycles. Evaluation occurred every 2 cycles. Primary endpoint was TTP; secondary endpoints include RR, PFS, OS, and toxicity. Results: 48 patients were enrolled; 56% were male and 96% were Caucasian. 33 patients were evaluable for response. There was 1 CR, 9 PR, 13 SD (48% disease control rate) and 10 PD. Median TTP was 3.37 months (95% CI 2.30 to 4.47 months). At the time of analysis, 13 patients were alive and with a median overall survival of 4.77 months (95% CI 3.67 to 6.07 months). 5 patients (10.4%) required dose reductions due to AEs, 2 due to fatigue, 1 due to neutropenia, 1 due to pancytopenia and 1 due to pneumonia. Grade 3/4 AEs included fatigue (18.8%), dyspnea (14.5%), infection without neutropenia (12.5%), anemia (8.3%), neutropenia (8.3%), and diarrhea (8.3%). Conclusions: These data indicate that single agent bendamustine appears to be well tolerated and effective in the second or third line setting for patients with SCLC.
A phase II trial of pazopanib in relapsed/refractory small cell lung cancer (SCLC).
Authors: Gandhi Leena , Heist Rebecca Suk , Lucca Joan Vern , Temel Jennifer S. , Fidias Panos , Morse Linda K. , Johnson Bruce E 
Published: March 2020

7099 Background: Despite response to initial therapy, SCLC has high rates of relapse or distant metastasis and limited 2nd-line therapeutic options. Angiogenesis is an essential part of cell invasion, dissemination, and outgrowth of distant metastases and therefore is a potential therapeutic target in SCLC. Pazopanib (Votrient, GSK) is a potent, competitive inhibitor of the tyrosine kinase activity of VEGFR-1, VEGFR-2, VEGFR-3, PDGF, and c-kit. We initiated a phase II single-arm trial of pazopanib in relapsed or refractory SCLC to determine impact on disease progression. Methods: Patients were eligible if they had progressive disease following up to two lines of prior therapy. Patients were treated at the FDA-approved dose of 800 mg pazopanib once daily. The primary endpoint was progression-free rate (PFR) at 8 weeks. Secondary endpoints included median progression-free survival, overall survival, and safety. The trial followed a Simon 2-stage design to limit accrual if no therapeutic benefit was observed. Results: To date, 27 of 30 planned subjects have been enrolled since October 2010. Two did not complete cycle 1 and were considered inevaluable for response. Major toxicities (mostly grade 1/2) were those previously described including nausea, fatigue, hypertension, electrolyte abnormalities, and AST/ALT elevations (grade 3 in 4 subjects). Three subjects were removed from study due to toxicity: 1 with grade 3 nausea, 1 with grade 3 drop in the cardiac ejection fraction, and 1 with multiple grade 2 toxicities including diarrhea, fatigue, and nausea. A fourth was removed due to grade 1 hemoptysis despite clinical response. The PFR at 8 weeks of 21 subjects evaluable for response to date was 52%; 4 of these 11 subjects had chemo-refractory disease. There were no confirmed responses, but tumor regressions ranged from 2-20%. Median progression-free survival is 14.1 weeks. Conclusions: In patients with SCLC, single-agent pazopanib demonstrated a notable rate of stable disease (including among chemo-refractory patients) and a median PFS that exceeds that of historical PFS rates of < 2 months on ineffective 2nd-line therapies. These data suggest that the potential for pazopanib in SCLC treatment should be further investigated.
Randomized phase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous NSCLC.
Authors: Ramalingam Suresh S. , Shtivelband Mikhail , Soo Ross A. , Barrios Carlos H. , Makhson Anatoly , Segalla J.G.M. , Pittman Kenneth B. , Kolman Petr , Pereira Jose Rodrigues , Srkalovic Gordan , Belani Chandra Prakash , Axelrod Rita , Owonikoko Taofeek Kunle , Qian Jiang , McKee Mark D. , Ricker Justin L. , Carlson Dawn M. , Gorbunova Vera A. 
Published: March 2020

7512 Background: Linifanib is a potent and selective inhibitor of VEGF and PDGF receptors with modest single-agent activity in NSCLC. We evaluated the combination of linifanib with carboplatin (C) and paclitaxel (P) for first-line therapy of advanced non-squamous NSCLC. Methods: Patients (pts) with stage IIIB/IV, non-squamous NSCLC, stratified by ECOG PS and gender, were randomized to receive up to six 3-wk cycles of C (AUC 6 mg/ml/min) and P (200 mg/m2) with daily placebo (Arm A), linifanib 7.5 mg (Arm B), or linifanib 12.5 mg (Arm C). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), 12 m survival rate, and objective response rate (ORR). Safety was assessed by NCI-CTCAE v3.0. Results: 138 pts were randomized at 37 sites in 6 countries. Baseline characteristics were: median age, 61 y; men, 57%; smoker, 84%. Efficacy results are shown in the table. Thrombocytopenia was the only Grade 3/4 AE significantly higher on linifanib (Arm B: 16.7%; Arm C: 29.8%) vs. placebo (2.1%). Other adverse events (AEs) related to the dose of linifanib were diarrhea, thrombocytopenia, hypertension, weight loss, palmar-plantar erythrodysaesthesia syndrome, and hypothyroidism. Analysis of samples for predictive biomarkers including serum VEGF and placental growth factor are underway. Conclusions: The addition of linifanib to chemotherapy was tolerable at the doses tested and resulted in a significant improvement in PFS, with a modest survival improvement for Arm C in first-line therapy of advanced non-squamous NSCLC. [Table: see text]
CALGB 30704: A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small cell lung cancer (NSCLC).
Authors: Heist Rebecca Suk , Wang Xiaofei F. , Hodgson Lydia , Otterson Gregory Alan , Stinchcombe Tom , Vokes Everett E. , Socinski Mark A. 
Published: March 2020

7513 Background: Second line chemotherapy improves survival modestly and new strategies are needed. This trial was designed to evaluate the paradigm of an anti-VEGF strategy with or without standard chemotherapy in previously treated NSCLC. Methods: Patients with Stage IIIB/IV NSCLC, PS 0-1 progressive after first-line chemotherapy were eligible for randomization to P (pemetrexed 500 mg/m2 d1), S (sunitinib 37.5 mg d1-21), or P+S (pemetrexed 500 mg/m2 d1 + sunitinib 37.5 mg d1-21). Pts were stratified by PS (0/1), stage (IIIB/IV), and gender (M/F). Primary objective was 18-week PFS rate; secondary objectives were response, OS, and toxicity. Target accrual was 225. The study was terminated early due to decreasing accrual rates. Results: Between 4/08 and 9/11, 130 pts registered; 128 pts treated (P=41, S=46, P+S=41). Median follow-up 99 weeks. Baseline characteristics in the three arms (P/S/P+S) were well balanced: Male (54%/54%/54%); PS 0 (32%/35%/34%); Stage IV (88%/83%/93%). Histology was predominantly adenocarcinoma (66%/57%/66%); squamous was allowed (10%/15%/15%). Toxicity was higher in the S-containing arms: Grade 3/4/5 hematologic toxicity: P 5/0/0 (12%), S 8/1/0 (21%), P+S 5/9/0 (36%); Grade 3/4/5 non-hematologic toxicity (excluding disease related deaths): P 6/2/0 (20%), S 21/3/1 (58%), P+S 21/3/1 (63%). The 18-week PFS rate in the three arms was: P 51% (38-69), S 36% (24-54), P+S 47% (34-65). There is an overall statistically significant difference in OS between the three arms (2-sided p=0.0179) with HR 0.65 (95%CI: 0.38-1.13) for P/S; HR 0.47 (95%CI: 0.27- 0.82) for P/P+S. Median OS was 10.5 mo (8.3-22.5) for P, 7.0 mo (6.0-13.0) for S, 6.7 (4.1-10.4) mo for P+S. Median PFS was 4.4 mo (1.7-8.8) for P, 3.3 mo (2.7-4.3) for S, 3.7 mo (2.5-4.3) for P+S (p=0.3). Fewer patients in the P+S arm received any subsequent therapy (29%) than either P (54%) or S (57%). Conclusions: Pemetrexed had a superior toxicity profile to either sunitinib or the combination of pemetrexed and sunitinib. OS was significantly better with P alone compared to the two S-containing arms, with P+S performing worst for OS.
Activity of cabozantinib (XL184) in metastatic NSCLC: Results from a phase II randomized discontinuation trial (RDT).
Authors: Hellerstedt Beth A. , Edelman Gerald , Vogelzang Nicholas J. , Kluger Harriet M. , Yasenchak Christopher A. , Shen Xiaodong , Ramies David A. , Gordon Michael S. , Lara Primo 
Published: March 2020

7514 Background: Dysregulation of MET and VEGFR2 signaling has been observed in NSCLC and MET upregulation has been implicated in resistance to EGFR inhibitors. Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2. A RDT evaluated activity and safety in 9 tumor types. Here we report on the metastatic NSCLC cohort which included patients who received prior EGFR and VEGF pathway targeted therapy. Methods: All eligible patients (pts) were required to have measurable disease at baseline. Pts received cabo at 100 mg qd over a 12 wk Lead-in stage. Tumor response (mRECIST) was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label cabo, pts with SD were randomized to cabo vs placebo, and pts with PD discontinued. Results: Enrollment to this cohort is complete (n = 60); all pts are unblinded. Baseline characteristics: median age 67 years; adenocarcinoma 72% and squamous cell 28%; 6 pts with known EGFR mutation (of 28 tested), all having received prior erlotinib; bone metastases 20%; median prior lines of therapy 3 (range 0 - 6); prior exposure to anti-EGFR therapy 50%, prior exposure to anti-VEGF pathway therapy 32%. Median follow-up was 2 months (range 0.4 - 22.3 months). At Wk 12, ORR per RECIST was 10% and overall disease control rate (PR+SD) was 40%. Objective tumor regression was observed in 30/47 pts (64%) with post-baseline tumor assessments, some of whom had known driver mutations in KRAS (3 pts) or EGFR (4 pts). 24 pts (40%) completed Lead-in stage with 15 randomized to continue cabo (N = 8) or to placebo (N = 7). No differences with respect to PFS were observed between treatment arms in the randomized phase of the study. Median PFS from study day 1 for all pts was 4.2 months. Most common Grade 3/4 AEs were fatigue (13%), Palmar-plantar erythrodyesthesia (8%), diarrhea (7%) and asthenia (7%); one related Grade 5 AE of hemorrhage was reported during Lead-in stage. Conclusions: Cabo treatment demonstrates activity in heavily pretreated metastatic NSCLC pts with 4.2 months median PFS, 10% RECIST response, and 64% rate of objective tumor regression. The safety profile of cabo was comparable to that seen with other VEGFR TKIs. Future studies are warranted in NSCLC.
Randomized phase III trial of S-1 plus cisplatin versus docetaxel plus cisplatin for advanced non-small-cell lung cancer (TCOG0701).
Authors: Katakami Nobuyuki , Gemma Akihiko , Sakai Hiroshi , Kubota Kaoru , Nishio Makoto , Inoue Akira , Okamoto Hiroaki , Isobe Hiroshi , Kunitoh Hideo , Takiguchi Yuichi , Kobayashi Kunihiko , Nakamura Yoichi , Ohmatsu Hironobu , Sugawara Shunichi , Minato Koichi , Fukuda Masaaki , Yokoyama Akira , Takeuchi Masahiro , Michimae Hirofumi , Kudoh Shoji ,   Tokyo Coopetative Oncology Group
Published: March 2020

7515 Background: Although molecularly targeted therapy improves outcome of selected patients with advanced non-small-cell lung cancer (NSCLC), most of the patients ultimately become candidates of cytotoxic chemotherapy, which is the cornerstone of patient management. S-1 plus cisplatin (SP) has shown activity and good tolerability in phase II settings. Docetaxel plus cisplatin (DP) is the only third-generation regimen that demonstrated statistically significant improvement of overall survival and quality of life by head to head comparison with a second-generation regimen, vindesine plus cisplatin, in patients with advanced NSCLC. Methods: Patients with previously untreated stage IIIB or IV NSCLC, an ECOG PS of 0-1 and adequate organ functions were randomized to receive either oral S-1 80 mg/m2/day (40 mg/m2 b.i.d.) on days 1 to 21 plus cisplatin 60 mg/m2 on day 8 every 5 weeks or docetaxel 60mg/m2 on day 1 plus cisplatin 80 mg/m2 on day 1 every 3 weeks, both up to 6 cycles. The primary endpoint is overall survival (OS). Non-inferiority study design was employed as upper confidence interval (CI) limit for HR<1.322. Secondary endpoints include progression-free survival (PFS), response, safety, and quality of life (QOL). Results: From April 2007 to December 2008, 608 patients from 66 sites in Japan were randomized to SP (n=303) or DP (n=305). Patient demographics were well balanced between the two groups. Two interim analyses were preplanned. At the final analysis, total of 480 death events were observed. The primary endpoint was met. OS for SP was non inferior to DP (median survival, 16.1 v 17.1 months, respectively; HR=1.013; 96.4% CI, 0.837-1.227). PFS was 4.9 months in the SP arm and 5.2 months in the DP arm. Statistically significantly lower rate of febrile neutropenia (7.4% v 1.0%), grade 3/4 neutropenia (73.4% v 22.9%), grade 3/4 infection (14.5% v 5.3%), grade 1/2 alopecia (59.3% v 12.3%) were observed in the SP arm than in the DP arm. QOL data investigated by EORTC QLQ-C30 and LC-13 favored for the SP arm. Conclusions: S-1 plus cisplatin is a standard first-line chemotherapy regimen for advanced NSCLC.
A randomized placebo-controlled phase III study of intercalated erlotinib with gemcitabine/platinum in first-line advanced non-small cell lung cancer (NSCLC): FASTACT-II.
Authors: Mok Tony , Wu Yi Long , Thongprasert Sumitra , Yu Chong-Jen , Zhang Li , Ladrera Guia Elena , Srimuninnimit Vichien , Sriuranpong Virote , Sandoval-Tan Jennifer , Zhu Yunzhong , Liao Meilin , Zhou Caicun , Pan Hongming , Lee Victor , Chen Yuh-Min , Sun Yan , Margono Benjamin , Jin Kate , Truman Matt , Lee Jin Soo 
Published: March 2020

7519^ Background: FASTACT, a randomized, phase 2 study in advanced NSCLC, found that intercalated erlotinib with 1st-line platinum-based chemotherapy (CT) significantly prolongs progression-free survival (PFS) (HR 0.47, p=0.0002) versus CT alone (Mok et al. JCO 2009). FASTACT-II is a confirmatory, randomized, phase 3, placebo-controlled, double-blind study in a large patient population Methods: Patients with untreated stage IIIB/IV NSCLC and ECOG PS 0/1 were randomized (1:1) to receive up to 6 cycles of gemcitabine (1,250 mg/m2 on d1 and 8) plus platinum (carboplatin 5×AUC or cisplatin 75 mg/m2 on d1) q4w, with either intercalated erlotinib (150 mg/day on d15–28) or placebo. Non-progressing patients received maintenance erlotinib or placebo until progression, unacceptable toxicity or death. Stratification was by disease stage, histology, smoking status and CT regimen. Primary endpoint was PFS; secondary endpoints included overall response rate (ORR), overall survival (OS), safety, QoL and biomarker analyses. Results: From Apr 2009 to Sep 2010, 451 patients were randomized to receive erlotinib (n=226) or placebo (n=225). Baseline demographics were well balanced across the arms; overall, 49% were never smokers, 40% were female and 76% had adenocarcinoma. PFS was significantly prolonged with erlotinib vs placebo: median 7.6 vs 6.0 months, respectively; HR 0.57 (95% CI 0.46–0.70); p<0.0001. ORR was significantly improved with erlotinib vs placebo: 42.9% vs 17.8%; p<0.0001. A non-significant trend towards longer OS was seen with erlotinib vs placebo (median 18.3 vs 14.9 months; HR 0.78 [95% CI 0.60–1.02]; p=0.069); 73% of placebo patients received a 2nd-line EGFR TKI. Except for skin rash with erlotinib, there was no clinically significant difference in toxicity between arms. A total of 283 patients (62.7%) provided samples for biomarker analyses, including EGFR mutation status, results of which will be presented. Conclusions: Intercalation of erlotinib with CT significantly prolonged PFS in 1st-line advanced NSCLC. Biomarker analysis will determine the significance of this regimen in patients with or without activating EGFR mutations.