First-line Advanced Non-small Cell Lung Research Articles

MSR29 Application of Bayesian Multi-Parameter Evidence Synthesis to Achieve Clinical Plausibility of Lifetime Survival Extrapolations in First-Line Advanced Non-Small Cell Lung Cancer (aNSCLC)

Lifetime overall survival (OS) extrapolations are required to estimate important differences in costs and benefits between comparators in health economic models. Bayesian multi-parameter evidence synthesis (B-MPES) models for aNSCLC patients receiving second-line nivolumab have previously demonstrated clinically reasonable and stable estimates for long-term OS. Here, we investigate the plausibility of B-MPES predictions for OS in the CheckMate 227 Part 1 trial of nivolumab plus ipilimumab (NIVO+IPI) in aNSCLC patients in the first-line setting and compare with uninformed standard parametric models (SPMs).

Long-term comparative efficacy and safety of nivolumab plus ipilimumab relative to other first-line therapies for advanced non-small-cell lung cancer: A systematic literature review and network meta-analysis

ObjectivesTo quantify the long-term comparative efficacy and safety of nivolumab in combination with ipilimumab (NIVO + IPI) relative to other immunotherapy (IO)-based regimens and chemotherapy in patients with first-line advanced non-small cell lung cancer (aNSCLC). MethodsPhase 3 randomized controlled-trials (RCTs) with minimum 3-year follow-up evaluating IO-based regimens approved for first-line aNSCLC were identified via systematic literature review. Analytic populations were defined by levels of PD-L1 expression and histology. Due to presence of proportional hazards violations, time-varying hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were estimated via Bayesian fractional polynomial network meta-analysis. For safety endpoints, odds ratios (ORs) were estimated using indirect treatment comparisons (ITCs). ResultsCheckMate 227, KEYNOTE-189, KEYNOTE-407, KEYNOTE-024, KEYNOTE-042, and IMpower150 were included in the base case analysis. For OS and PFS, HRs of NIVO + IPI relative to other IO-based regimens trended downward over time across analytic populations. The 36-month OS HRs of NIVO + IPI versus comparators were: 0.69 (95 % credible interval: 0.47, 1.00) versus pembrolizumab + chemotherapy and 0.65 (0.45, 0.93) versus atezolizumab + bevacizumab + chemotherapy in the non-squamous and PD-L1 all-comers population; 0.73 (0.53, 1.02) versus pembrolizumab + chemotherapy in the squamous and PD-L1 all-comers population; and 1.05 (0.83, 1.32) versus pembrolizumab in the mixed histology and PD-L1 ≥ 50 % population. For PFS, 36-month HR point estimates ranged from 0.46 to 0.85 (only statistically significant versus pembrolizumab + chemotherapy in the squamous population; 0.46 [0.31, 0.69]). Adverse events (AEs) leading to discontinuation were not statistically significantly different between NIVO + IPI and pembrolizumab + chemotherapy, nor between NIVO + IPI and pembrolizumab monotherapy, although treatment-related grade ≥ 3 AEs were higher with NIVO + IPI than pembrolizumab monotherapy (OR = 2.21 [1.30, 3.75]). ConclusionsThis study indicates trends towards long-term benefit with NIVO + IPI compared with other IO-based combinations, with manageable toxicities.

Correlations between objective response rate and survival-based endpoints in first-line advanced non-small cell lung Cancer: A systematic review and meta-analysis

IntroductionThe study objective was to estimate the relationship between objective response and survival-based endpoints by drug class, in first-line advanced non-small cell lung cancer (aNSCLC). Materials and methodsA systematic literature review identified randomized controlled trials (RCTs) of first-line aNSCLC therapies reporting overall survival (OS), progression-free survival (PFS), and/or objective response rate (ORR). Trial-level and arm-level linear regression models were fit, accounting for inclusion of immunotherapy (IO)-based or chemotherapy-only RCT arms. Weighted least squares-based R2 were calculated along with 95% confidence intervals (CIs). For the main trial-level analysis of OS vs. ORR, the surrogate threshold effect was estimated. Exploratory analyses involved further stratification by: IO monotherapy vs. chemotherapy, dual-IO therapy vs. chemotherapy, and IO + chemotherapy vs. chemotherapy. ResultsFrom 17,040 records, 57 RCTs were included. In the main analysis, trial-level associations between OS and ORR were statistically significant in both the IO-based and chemotherapy-only strata, with R2 estimates of 0.54 (95% CI: 0.26–0.81) and 0.34 (0.05–0.63), respectively. OS gains associated with a given ORR benefit were statistically significantly larger within IO vs. chemotherapy comparisons compared to chemotherapy vs. chemotherapy comparisons (p < 0.001). Exploratory analysis suggested a trend by IO type: for a given change in ORR, ‘pure’ IO (IO monotherapy and dual-IO) vs. chemotherapy RCTs tended to have a larger OS benefit than IO + chemotherapy vs. chemotherapy RCTs. For ORR vs. PFS, trial-level correlations were strong in the IO-based vs. chemotherapy (R2 = 0.84; 0.72–0.95), and chemotherapy vs. chemotherapy strata (R2 = 0.69; 0.49–0.88). For OS vs. PFS, correlations were moderate in both strata (R2 = 0.49; 0.20–0.78 and R2 = 0.49; 0.23–0.76). ConclusionThe larger OS benefit per unit of ORR benefit in IO-based RCTs compared to chemotherapy-only RCTs provides an important addition to the established knowledge regarding the durability and depth of response in IO-based treatments.

Up-front cell-free DNA next generation sequencing improves target identification in UK first line advanced non-small cell lung cancer (NSCLC) patients

BackgroundGenomic sequencing is necessary for first-line advanced non-small cell lung cancer (aNSCLC) treatment decision-making. Tissue next generation sequencing (NGS) is standard but tissue quantity, quality, and time-to-results remains problematic. Here, we compare upfront cell-free-DNA (cfDNA) NGS clinical utility against routine tissue testing in patients with aNSCLC. MethodscfDNA-NGS was performed in consecutive, newly identified aNSCLC patients between December 2019–October 2021 alongside routine tissue genotyping. Variants were interpreted using AMP/ASCO/CAP guidelines. The primary endpoint was tier-1 variants detected on cfDNA-NGS. cfDNA-NGS results were compared to tissue results. ResultsOf 311 patients, 282 (91%) had an informative cfDNA-NGS test; 118 (38%) patients had a tier-1 variant identified by cfDNA-NGS. Of 243 patients with paired tissue-cfDNA tests, 122 (50%) tissue tests were informative; 85 (35%) tissue tests identified a tier-1 variant. cfDNA-NGS detected 39 additional tier-1 variants compared to tissue alone, increasing the tier-1 detection rate by 46% (from 85 to 124). The sensitivity of cfDNA-NGS relative to tissue was 75% (25% tissue tier-1 variants were not detected on cfDNA-NGS); 33% of cfDNA tier-1 variants were not identified on tissue tests. Median time from request-to-report was shorter for cfDNA-NGS versus tissue (8 versus 22 days; p < 0.0001).A total of 245 (79%) patients received first-line systemic-therapy: 49 (20%) with cfDNA-NGS results alone. Median time from sampling-to-commencement of first-line treatment was shorter for cfDNA-NGS blood draw versus first tissue biopsy (16 versus 35 days; p < 0.0001). ConclusionscfDNA-NGS increased the tier-1 variant detection rate with high concordance with tissue, and halves time-to-treatment. ‘Plasma-first’ upfront cfDNA-NGS use should be considered routinely for aNSCLC.

First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in advanced non-small cell lung cancer: a subanalysis of Asian patients in CheckMate 9LA

BackgroundCheckMate 9LA, a phase 3, randomized, open-label study in first-line advanced non-small cell lung cancer (NSCLC), showed significantly improved overall survival (OS) with nivolumab plus ipilimumab combined with 2 cycles of chemotherapy versus chemotherapy alone (4 cycles). We present results for the Asian subpopulation enrolled in Japan and China.MethodsPatients aged ≥ 18 years with treatment-naive, histologically confirmed stage IV or recurrent NSCLC, Eastern Cooperative Oncology Group performance status 0–1 and no sensitizing EGFR/ALK mutations were randomized 1:1 to nivolumab [360 mg every 3 weeks (Q3W)] plus ipilimumab (1 mg/kg Q6W) combined with chemotherapy (Q3W for 2 cycles), or chemotherapy alone (Q3W for 4 cycles). Primary endpoint was OS; secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).ResultsTwenty-eight patients received nivolumab plus ipilimumab combined with chemotherapy and 30 received chemotherapy. At a minimum follow-up of 12.7 months, median OS was not reached with nivolumab plus ipilimumab combined with chemotherapy versus 13.3 months with chemotherapy [hazard ratio (HR) 0.33; 95% confidence interval (CI) 0.14–0.80]. Median PFS was 8.4 versus 5.4 months (HR 0.47; 95% CI 0.24–0.92) and ORR was 57% versus 23%, respectively. Grade 3–4 treatment-related adverse events were observed in 57% versus 60% of patients, respectively.ConclusionConsistent with results in the all randomized population, nivolumab plus ipilimumab combined with chemotherapy improved efficacy in the Asian subpopulation versus chemotherapy alone and had a manageable safety profile, supporting its use as first-line treatment for advanced NSCLC in Asian patients.

Real-world outcomes of immunotherapy–based regimens in first-line advanced non-small cell lung cancer

BackgroundFirst-line (1L) immunotherapy (I-O) has improved outcomes in patients with advanced non-small cell lung cancer (NSCLC) in clinical trials and is now routinely used alone or combined with chemotherapy. Although efficacy and safety of I-O therapies have been established in clinical trials, little is known about their performance and long-term efficacy in the real-world setting. We aimed to characterize real-world outcomes for patients with advanced NSCLC treated with 1L I-O therapy in the United States. MethodsPatients aged ≥18 years with confirmed advanced (stage III–IV) NSCLC who received either 1L I-O monotherapy or single-agent I-O combined with chemotherapy on or after January 1, 2016 were identified from the Flatiron Health database. Primary objectives were to examine overall survival (OS) and real-world progression-free survival. Index date was defined as date of 1L treatment initiation; data cut-off date was June 30, 2020. ResultsAmong 4271 patients receiving I-O plus chemotherapy, median OS was 10.6 (95 % confidence interval [CI], 9.3–11.8) months in patients with squamous NSCLC (n=814) and 12.0 (95 % CI, 11.3–12.8) months in those with non-squamous disease (n=3457). Regardless of histology, patients with high (≥50 %) tumor programmed death ligand 1 (PD-L1) expression demonstrated longer median OS vs those with low expression. Among 3041 patients receiving I-O monotherapy, median OS was 11.3 (95 % CI, 9.8–12.8) months in patients with squamous NSCLC (n=875) and 14.1 (95 % CI, 12.4–15.8) months in those with non-squamous disease (n=2166). OS benefit appeared to be greatest in the ≥50 % tumor PD-L1 expression group of the non-squamous cohort. ConclusionSurvival estimates were generally lower than those reported in pivotal clinical trials. These findings indicate that there remains room for improvement of real-world survival outcomes in patients with advanced NSCLC who receive 1L I-O–based regimens and for identification of subgroups of patients not benefitting from treatment with current I-O regimens.

MO01.06 Real-World Outcomes of Immunotherapy-Based Regimens in First-Line Advanced Non-Small Cell Lung Cancer

MO01.06 Real-World Outcomes of Immunotherapy-Based Regimens in First-Line Advanced Non-Small Cell Lung Cancer

Platinum-based chemotherapy (chemo) with CS1001, an anti-PD-L1 antibody, for first-line advanced non-small cell lung cancer (NSCLC): Preliminary results from phase Ib cohorts of CS1001-101 study.

e21687 Background: Immuno-oncology (IO) monotherapy or combination with platinum-based chemo is the current standard of care for pts with PD-L1 expression ≥ 50% and EGFR, ALK, ROS1, BRAF negative advanced NSCLC in China. CS1001-101 phase Ib study is to evaluate the efficacy and safety of CS1001, anti-PD-L1 mAb, in pts with solid tumors or lymphomas. Here we present the results of 2 cohorts: CS1001 plus platinum-based chemo for 1L advanced NSCLC. Methods: Pts with non-squamous (nsq)-NSCLC received 4-6 cycles of CS1001 (1200 mg, IV, Q3W), carboplatin (AUC = 5), and pemetrexed (500 mg/m2), followed by maintenance therapy with CS1001 and pemetrexed. Pts with squamous (sq)-NSCLC received CS1001 (1200 mg, IV, Q3W), carboplatin (AUC = 5), and paclitaxel (175 mg/m2), followed by maintenance therapy with CS1001. Results: By July 1st, 2019, 21 nsq-NSCLC and 20 sq-NSCLC pts were treated, with a median treatment duration of 135 and 109 days, respectively. 15 nsq-NSCLC pts remained on the study and 6 discontinued CS1001, 5 due to progressive disease (PD). 17 sq-NSCLC pts remained on the study and 3 discontinued CS1001, 2 due to adverse events (AEs). 10 had partial response (PR) in each cohort, leading to a response rate of 47.6% (nsq) and 58.8% (sq). The median duration of response (mDoR) and median progression-free survival (mPFS) were not reached (Table). In nsq-NSCLC cohort, 18 (85.7%) had CS1001-related AEs and 6 (28.6%) had G≥3 TRAEs. irAEs occurred in 5 pts with the most frequent ones being aspartate aminotransferase (AST) increased (4, ≤G2) and alanine aminotransferase (ALT) increased (3, ≤G2). 18 (90.0%) sq-NSCLC pts had CS1001-related AEs and 5 (25%) had G≥3 TRAEs. irAEs occurred in 3 pts with the most frequent ones being rash (2, ≤G2). AEs that led to CS1001 withdrawn only occurred in 2 sq-NSCLC pts, which were not related to CS1001. Conclusions: The combination of CS1001 and platinum-based chemo regimen demonstrated promising anti-tumor activity with a tolerable safety profile. The results of this study support further evaluation of CS1001 and platinum-based chemo in 1L NSCLC. Currently, a randomized phase III study (NCT03789604) of this treatment regimen in pts with chemo-naive advanced NSCLC is recruiting pts in China. Clinical trial information: NCT03312842. [Table: see text]

P1.01-91 A Phase I Study of Fixed Dose Vinorelbine and Escalating Doses of Ifosfamide in First-Line Advanced Non-Small Cell Lung Cancer

P1.01-91 A Phase I Study of Fixed Dose Vinorelbine and Escalating Doses of Ifosfamide in First-Line Advanced Non-Small Cell Lung Cancer

Systematic analysis of design and stratification for phase III trials in first-line advanced non-small cell lung cancer.

A recent study reviewed phase III trials of first-line advanced non-small cell lung cancer (NSCLC) conducted from 1981 to 2010, and provided trends in the study outcome. However, such trials have never been analyzed in detail for design and stratification factors. Phase III studies of systemic treatment for first-line advanced or metastatic NSCLC published in English literature between 1981 and 2010 were identified. Characteristics, including sample size, number of trials, region, rate of meeting accrual goal, primary endpoint, type of phase III, interim analysis, allocation method, and stratification factors, were determined for each decade. A total of 162 studies met the criteria. The number of studies and sample size increased over the three decades. The primary endpoint was reported more frequently in recent decades, and non-overall survival endpoints were chosen in European and Asian studies. Interim analysis was conducted more commonly during the 2000s. Allocation method was rarely reported throughout the three decades. The number of stratification factors increased significantly from one in 1980s to three in 2000s. Performance status, stage, and institution were most frequently selected, and at least one of the three factors was used in most of the studies in the 2000s. However, there are many other stratification factors that were used infrequently. Despite Consolidated Standards of Reporting Trials guidelines, allocation method has rarely been reported. The choice of stratification factor remains inconsistent across studies.

A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis comparing nab-paclitaxel plus carboplatin (nab-PC) with solvent-based paclitaxel plus carboplatin (sb-PC) in first-line advanced non-small cell lung cancer (NSCLC).

e19004 Background: To compare the quality-adjusted survival of nab-PC vs sb-PC in first-line advanced NSCLC, the Q-TWiST methodology was applied to a Phase 3 randomized clinical trial which showed a significantly higher ORR, the primary endpoint, and non-inferior PFS and OS for nab-PC (Socinski et al, 2012). Methods: OS was partitioned into time: before disease progression without grade ≥ 3 toxicity (TWiST); with grade ≥ 3 toxicity (TOX); and after progression (REL). Mean Q-TWiST was calculated by multiplying the time spent in each state by utilities to estimate the quality-adjusted OS. In the base case, the health state utilities were assigned TWiST=1; TOX=0.5; REL=0.5. In threshold analyses, TOX and REL utilities were varied from 0 to 1. Comparisons between treatments were made for the intent-to-treat (ITT) population and subgroups by age, region, histology, and stage. Nonparametric bootstrap 95% CIs were derived to assess the statistical significance of differences in Q-TWiST. A relative gain in Q-TWiS...

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.

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&lt;0.0001. ORR was significantly improved with erlotinib vs placebo: 42.9% vs 17.8%; p&lt;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.

Clinical experience with carboplatin (CBDCA) and oral vinorelbine (NVBO) in first-line advanced non-small cell lung cancer (NSCLC) treatment.

e18143 Background: A study reported in the literature including p with advanced NSCLC showed a strong patient (p) preference for PO treatment while maintaining the efficacy and a good safety profile. As results, two Spanish institutions decided to prescribe the oral form of vinorelbine when administered together with CBDCA in patients unfit to receive cisplatin. Methods: Between May 2008 and June 2009, 17 chemo-naïve p with histologically confirmed stage IIIB/IV NSCLC and unfit to receive cisplatin were treated in 2 Spanish institutions. Treatment consisted of CBDCA AUC5 day 1 plus NVBO 80 mg/m2 days 1 and 8, with a prior test of myelosensitivity at 60 mg/m2 for the first cycle (cy), every 21 days, for a maximum of 6 cy unless progression of the disease was observed earlier. Results: Patient's characteristics were: Median age, 69 years (range 55-82); males, 94%; smokers, 75%; PS 0-1, 94%; adenocarcinoma, 25%/squamous, 69%; stage IIIB, 17.6%/IV, 82.4%. Median number of cy 4 (range 1-6). We analyzed 70 cy. Cycle 2 dose escalation to 80 mg/m2 was performed in 76.5% of p. Hematological toxicities (%p): grade (g) 3/4 neutropenia, 35.3%; g3 anemia, 11.8%. Nonhematological toxicities (%p): respiratory g4, 5.9%; fever g4, 5.9% pain g4, 5.9%; nausea and vomiting g3, 5.9%. 16 p were evaluable for response. 5 PR (31%) and 7 SD (44%) were reported. With a median follow-up of 5.1 months (m), median survival for the whole population was 9.6 m, progression free survival 8 m. Conclusions: The findings of this retrospective analysis when compared to the reported data in the literature in this population suggest that the combination of carboplatin either plus oral or intravenous vinorelbine have a similar efficacy. The use of oral vinorelbine avoids venous toxicity and adds comfort to the day 8 administration. No significant financial relationships to disclose.

Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study.

Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC) patients with good performance status (PS). Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR), secondary endpoints toxicity and time to progression (TTP). Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females) 10% (2/21) had stage IIIB, 90% (19/21) stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks), median overall survival (OS) 8 months (range 1–27 months), 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might, therefore, be a treatment option for NSCLC patients with high ERCC1 expression.

New Horizons in Chemotherapy: Platforms for Combinations in First-Line Advanced Non-small Cell Lung Cancer

The treatment of advanced non-small cell lung cancer has evolved substantially during the last decade. Chemotherapy with a platinum-based doublet prolongs survival and improves quality of life in patients with good performance status. Recently, the addition of bevacizumab and the use of epidermal growth factor receptor inhibitors in appropriately selected patients have further improved the outcome of patients with advanced non-small cell lung cancer. Newer targeted agents are being developed and tested in the clinical arena at a rapid pace. In addition, the identification by clinical or molecular criteria of patient populations that benefit the most from these agents is under active investigation. In contrast, the development of newer cytotoxic agents, with innovative mechanisms of action, has been comparatively disappointing. Whether standard cytotoxic drugs are required as newer biologic agents are more frequently used or whether a more active and safer chemotherapy can be used as a template for combinations with biologic agents remains an important research topic.

Resource utilization by non-small cell lung cancer histology: Results from the randomized, phase III trial of pemetrexed/cisplatin versus gemcitabine/cisplatin

8097 Background: Efficacy results from the phase III trial of pemetrexed/cisplatin (PC) versus gemcitabine/cisplatin (GC) for first-line advanced non-small cell lung cancer (NSCLC) demonstrated non...

Phase II trial of satraplatin (S) and paclitaxel (P) in first-line advanced non-small cell lung cancer (NSCLC) treatment: Final results

19023 Background: In a prior phase I trial we combined a new oral platinum analogue (S) with P in patients (pts) with refractory malignancies, and found this regimen to be safe (Invest New Drugs 20...

Phase II trial of oxaliplatin and gemcitabine with bevacizumab in first-line advanced non-small cell lung cancer (NSCLC)

17009 Background: Oxaliplatin-Gemcitabine (GemOx) is an active and well tolerated. Bevacizumab (BV) prolongs survival when combined with carboplatin-paclitaxel. This phase II trial evaluates the efficacy of GemOx + BV as 1st line therapy for advanced NSCLC patients. Methods: Pts with stage IIIB (effusion) and IV non-squamous NSCLC, ECOG PS 0 or 1, no CNS metastasis, and no other contraindications to BV, are eligible. Prior therapy for earlier-stage disease allowed if completed at least 12 months before enrollment. Treatment consists of Gem 1000 mg/m2 on d1 and 8, Ox 130 mg/m2 on d1, and BV 15 mg/kg on d1, repeated every 3 wks for a total 4 cycles. Pts who respond or have stable disease receive BV maintenance until progression. Main endpoints are response rate (RR), grade (Gr) 3–4 toxicities, time to progression (TTP), and overall survival (OS). Results: As of 12/05, 26 out of 50 projected pts have been enrolled from 4 institutions. M/F 17/9; median age 65y (45,81); IIIB/IV 3/23; PS 0/1 8/18. Median F/U time is 3.7 months. 24 pts are evaluable for toxicity: 1Gr3 ANC; 1Gr3 and 4 PLT; no FN.3 Gr3 diarrhea and 2 Gr3 N/V; 1Gr3 and 4 hypophosphatemia; 1 pt had ischemic bowel after the 1st cycle, recovered fully and was removed from study; 1 pt died of liver failure in the 1st cycle. No bleeding complications have occurred. 22 pts are evaluable for RR (ITT): 7 PR (31%); 8 SD (36%). TTP and OS data not yet available. Conclusions: This is the first report of GemOx in combination with BV in advanced NSCLC. This regimen has minimal hematologic toxicity but selected non-hematologic toxicities are noted. Activity appears promising and merits further investigation. Accrual is ongoing. [Table: see text]