Maintenance Pemetrexed Research Articles

Efficacy and Toxicity of Maintenance Pemetrexed Following Induction Treatment with Pemetrexed Plus Cisplatin for Advanced Non-small-cell Non-squamous Carcinoma of the Lung

Abstract INTRODUCTION: The aim of this study is to assess the efficacy and toxicity of maintenance pemetrexed following induction treatment with cisplatin and pemetrexed for patients with advanced non-small cell lung cancer. PATIENTS AND METHODS: Eligible patients following four cycles of intravenous pemetrexed (Alimpta©; 500 mg/m2) and intravenous cisplatin (75 mg/m2) were given 21-day cycles of maintenance pemetrexed (500 mg/m2) until disease progression, unacceptable adverse event or death. From a total 80 patients receiving palliative induction chemotherapy, 17 subsequently received maintenance pemetrexed. RESULTS: The mean number of maintenance cycles completed was 5.9 (range 1-20; median 3.0). The mean progression-free survival (PFS) was 5.2 months (range: 2-15; median: 2.0) and the 1-year PFS was 17%. Treatment was discontinued due to disease progression (71%), adverse event (21%) and death from study disease (7%). Grade 3-4 laboratory and non-laboratory adverse events were seen in 11.8 and 17.6% of patients, respectively. Anaemia was the most common adverse event (71% of all patients; 65% grade 1-2; 5.9% grade 3-4). The most common reason for withdrawal due to adverse event was declining renal function. There was a statistically significant correlation between worsening performance status and reducing number of maintenance cycles completed (Spearman’s rank; R = −0.511, p = 0.036). DISCUSSION: The median PFS was lower than in previous studies with a higher than previously reported frequency of adverse events. Clinicians must monitor renal function and full blood counts vigilantly, especially in patients with performance status greater than 0.

131P - Duration and Tolerance of Maintenance Pemetrexed (MPEM) Treatment for Advanced Non-Small Cell Lung Cancer

131P - Duration and Tolerance of Maintenance Pemetrexed (MPEM) Treatment for Advanced Non-Small Cell Lung Cancer

60: Discontinuation of maintenance pemetrexed (mPEM) in non-small cell lung cancer (NSCLC) due to renal failure

60: Discontinuation of maintenance pemetrexed (mPEM) in non-small cell lung cancer (NSCLC) due to renal failure

Cisplatin/Pemetrexed Followed by Maintenance Pemetrexed Versus Carboplatin/Paclitaxel/Bevacizumab Followed by Maintenance Bevacizumab in Advanced Nonsquamous Lung Cancer: The GOIM (Gruppo Oncologico Italia Meridionale) ERACLE Phase III Randomized Trial

IntroductionCisplatin with pemetrexed (CP) and carboplatin with paclitaxel and bevacizumab (CbTB) are standard first-line treatments for patients with advanced nonsquamous (NS) non–small-cell lung cancer (NSCLC). Quality of life (QoL) is a key objective in the management of advanced NSCLC. Thus, effect on QoL could be an additional factor in the choice of treatment. Patients and MethodsPatients with untreated stage IIIB/IV NS-NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomized to receive first-line chemotherapy with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2, every 3 weeks, for 6 cycles followed by maintenance pemetrexed; or carboplatin area under the curve 6, paclitaxel 200 mg/m2, and bevacizumab 15 mg/kg, every 3 weeks, for 6 cycles followed by maintenance bevacizumab. The primary end point was the difference in QoL between the 2 treatment arms after 12 weeks of maintenance, measured using the EuroQoL 5 Dimensions-Index (EQ5D-I) and EQ5D-visual analogue scale (EQ5D-VAS). ResultsOne hundred eighteen patients were randomized to CP (n = 60) or CbTB (n = 58). Baseline characteristics were well balanced. The proportion of patients evaluable for the primary end point was lower than planned. After 12 weeks of maintenance, the difference between mean changes in EQ5D-I was 0.137, favoring CP (95% confidence interval [CI], −0.02 to 0.29, Wilcoxon P = .078), although not statistically significant; and the difference between mean changes in EQ5D-VAS was 0.97 (95% CI, −9.37 to 11.31, Wilcoxon P = .41). ConclusionAlthough the study was underpowered because of a small number of patients evaluable for the primary end point, QoL did not differ between treatment arms. Other factors such as comorbidities and schedule should be used when deciding on first-line treatment.

Phase II study of pemetrexed and carboplatin plus bevacizumab, followed by maintenance pemetrexed and bevacizumab in Japanese patients with non-squamous non-small cell lung cancer.

The present study evaluated the efficacy and safety of pemetrexed, carboplatin and bevacizumab, followed by maintenance pemetrexed and bevacizumab, in chemotherapy-naïve patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). The patients were administered pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve, 6.0 mg/ml × min) and bevacizumab (15 mg/kg) intravenously every three weeks for up to six cycles. Patients who did not experience tumor progression remained on maintenance pemetrexed and bevacizumab until disease progression or unacceptable toxicity occurred. The primary endpoint was the overall response rate. Of the 26 patients enrolled between March 2010 and April 2011, three were excluded due to brain metastases, therefore the intention-to-treat (ITT) population consisted of 23 patients. The median age was 64 years (range, 40–74 years) and 15 patients were male. In total, six patients had a performance status of 0, and 20 had stage IV tumors. The response rate was 69.6% [95% confidence interval (CI), 47.1–86.8], the disease control rate was 100% and the time to response was 1.2 months (95% CI, 0.72–1.93). The median progression-free survival time was 8.6 months (95% CI, 5.9–10.9) and the median overall survival time was 18.6 months (95% CI, 12.9–24.8). There were no grade 3 or worse hemorrhagic events and the feasibility was modest. Overall, pemetrexed and carboplatin plus bevacizumab, followed by maintenance pemetrexed and bevacizumab, was effective and tolerable in the patients with non-squamous NSCLC, and the time to response was relatively short.

471P - Effect of Nintedanib (Bibf 1120) Combined with Standard 2Nd-Line Docetaxel in Nsclc Patients Who Received Prior Pemetrexed in Lume-Lung 1: a Randomised, Placebo-Controlled Phase III Trial

ABSTRACT Aim: Nintedanib (N) is an oral, triple angiokinase inhibitor of VEGF, PDGF and FGF signalling. Primary analysis of the LUME-Lung 1 trial (NCT00805194; 1199.13) showed a significant improvement in PFS with N + docetaxel (D) in NSCLC patients (pts) regardless of histology; OS was also significantly improved in adenocarcinoma (adeno) pts. Pemetrexed (PEM) is a standard 1st-line and maintenance treatment for nonsquamous NSCLC pts. To determine whether prior PEM would influence outcomes of pts in LUME-Lung 1, we evaluated the efficacy and safety of N + D in pts who received 1st-line and maintenance PEM. Methods: 1314 pts with Stage IIIB/IV recurrent NSCLC were randomised to receive either N 200 mg bid + D 75 mg/m2 q21d (n = 655) or placebo (Pl) + D (n = 659) in LUME-Lung 1. Retrospective subgroup analyses according to prior PEM treatment (1st line or maintenance) were performed to determine OS and safety. Results: The percentage of pts with adeno tumour histology who were treated 1st line with PEM along with platinum was approximately 19% (N arm, n = 61; Pl arm, n = 65). Pt characteristics were balanced across groups. OS results according to receipt of any PEM 1st-line and maintenance therapy for adeno pts are shown in the table. For all pts and those with adeno histology in particular, no significant difference in OS was noted between those who did or did not receive PEM; no significant interaction between treatment groups and any PEM treatment was observed. Further, slightly more pts in the N arms across all subgroups experienced grade ≥3 adverse events; diarrhoea and reversible increases in liver enzymes occurred more frequently in pts in both N arms. OS results in NSCLC pts with adeno histology who received 1st-line and/or maintenance PEM No PEM 1st-line PEM 1st-line No maintenance PEM 1st-line Maintenance PEM 1st-line N n = 261 Pl n = 271 N n = 61 Pl n = 65 N n = 309 Pl n = 322 N n = 13 Pl n = 14 Median OS, months 13.4 10.8 12.0 8.0 12.6 10.0 18.9 12.8 HR (95% CI); p-value 0.83 (0.68–1.00); p = 0.05 0.79 (0.53–1.18); p = 0.25 0.84 (0.70–1.00); p = 0.05 0.78 (0.30–2.07); p = 0.62 Interaction between treatment & subgroup variable, p-value p = 0.9026 p = 0.7162 Conclusions: On-study treatment with N + D resulted in a comparably favourable improvement in OS regardless of whether pts with adeno tumours were treated 1st line with a PEM- or non-PEM-containing platinum doublet. Disclosure: A. Mellemgaard: Advisory Board: Boehringer Ingelheim; J. von Pawel: Advisory Board/Consultant: AbbVie, Clovis, Daiichi Sankyo, Novartis, Pfizer, Vertex Pharmaceuticals; J. Barrueco: Employee: Boehringer Ingelheim Pharmaceuticals Inc., USA; H. Buchner, J. Hocke and R. Kaiser: Employee: Boehringer Ingelheim Pharma GmbH KG, Germany;S. Novello: Advisory Board/Honoraria/Invited Speaker: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Roche; J. Douillard: Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck Serono, Roche; Educational Symposia: Amgen, AstraZeneca, Bayer; Research Grants: Merck Serono; M. Reck: Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Hoffmann-la Roche, Lilly, Novartis, Pfizer. All other authors have declared no conflicts of interest.

A Randomized Phase III Study of Docetaxel Plus Cisplatin Versus Pemetrexed Plus Cisplatin in First Line Non-Squamous Non-Small Cell Lung Cancer (Nsq-Nsclc)

ABSTRACT Aim: For patients with NSq-NSCLC, pemetrexed(A) plus cisplatin(P) was superior to gemcitabine(G) plus cisplatin(P) in terms of efficacy and toxicity. However, there have been no prospective phase III trial directly comparing the efficacy of AP with docetaxel + cisplatin (DP) in NSq-NSCLC. The objective of this study is to prove the non-inferiority of progression free survival (PFS) of DP compared to AP. Methods: We undertook an open-label phase III trial with recruitment between August 2011, and December 2013, at 14 centers in Korea. Patients with chemotherapy-naive NSq-NSCLC were randomized into 3 weekly cisplatin 70 mg/m2 with either docetaxel 60mg/m2 (DP) or pemetrexed 500mg/m2 (AP) for up to 4 cycles with stratification strata of performance status and sex. The primary objective was to assess PFS and the secondary endpoints were response rate, overall survival (OS) and safety. Treatment response was evaluated according to RECIST version 1.1. Results: After 149 patients were randomized into AP (n = 77) and DP (n = 72) arm, study team finished enrollment because of approval and popular use of maintenance pemetrexed treatment in Korea. Clinical characteristics including sex, age, and performance status were well balanced between the arms. Number of cycles and relative dose intensity were not significantly different between the arms. Partial remission was observed in 24 (31.2%) and 24 (33.3%) cases of AP and DP group, respectively. Median PFS was 4.7 months (95% confidence interval, CI 4.4 ∼ 5.1) in AP arm and 4.6 months (3.7 ∼ 5.6) in DP arm. Rate of grade 3 or 4 neutropenia and febrile neutropenia, number of serious adverse events were significantly higher in DP compared to AP arm (Table 1). Conclusions: Although both regimens showed similar PFS and response rate, more frequent adverse events and higher toxicities were observed in DP arm. (ClinicalTrials.gov Identifier: NCT01282151) Disclosure: Y. Kim: This study was funded by Sanofi Aventis Korea. All other authors have declared no conflicts of interest. Comparison of treatment, response, and adverse events. Pemetrexed/Cisplatin (n = 77) Docetaxel/Cisplatin (n = 72) Age, mean(SD) 63.0 ± 8.9 63.8 ± 9.8 Sex 53/24 50/22 ECOG PS (0/1/2) 14/55/8 17/48/7 Histology ADC/LCC/NSCLC 75/0/2 69/1/2 Stage (IIIB/IV) 5/72 3/69 Cycles (1/2/3/4/6) 7/16/2/49/3 11/14/1/45/1 Cycles mean(range) 3.4 (1-6) 3.2 (1-6) Total number of Cycles 259 228 Cycles delayed 17 (6.7%) 18 (7.9%) Doses reduced 16 (6.3%) 21 (9.3%) Relative dose-intensity (%) 97.6 ± 5.7 96.2 ± 6.9 Response (PR/SD/PD/NE) 24/33/10/10 24/25/15/8 PFS (m) 4.7 (4.4-5.1) 4.6 (3.7-5.6) Overall survival (m) 19.7 (10.8-28.6) 28.0 (7.5-48.5) Neutropenia grade 3/4 1 (1.3%) 10 (13.9%) ** Febrile Neutropenia 1 (1.3%) 8 (11.1%) * Total number of SAE 42 (16.2%) 70 (30.7%) *** SAE cases 17 (22.1%) 29 (40.3%) * * p

Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials

ObjectivesTwo phase III trials of advanced NSCLC patients were compared to examine relative efficacy and safety of differing treatment regimens. The JMDB trial investigated first-line pemetrexed–cisplatin (pemetrexed 500mg/m2 plus cisplatin 75mg/m2 every 21 days; maximum: 6 cycles). The PARAMOUNT phase III trial compared maintenance pemetrexed versus placebo after patients with nonsquamous NSCLC completed 4 cycles of first-line pemetrexed–cisplatin without disease progression. MethodsOverall survival (OS) and progression-free survival (PFS), analyzed by Kaplan–Meier and Cox methods, and toxicity rates were compared between the PARAMOUNT arms and a selected homogeneous population from JMDB: 346 patients with disease and prior treatment characteristics matching the PARAMOUNT population. ResultsOutcomes for the PARAMOUNT placebo arm were similar to the JMDB homogeneous group (median PFS: 5.6 versus 6.2 months, p=0.117, HR=1.16; median OS: 14.0 versus 14.2 months, p=0.979, HR=1.00). The PARAMOUNT maintenance pemetrexed group had statistically superior efficacy compared with the JMDB homogeneous group (median PFS: 7.5 versus 6.2 months, p<0.00001, HR=0.66; median OS: 16.9 versus 14.2 months, p=0.003, HR=0.75). Patients who received pemetrexed maintenance (median 4 cycles, range 1–44) following 4 cycles of pemetrexed–cisplatin exhibited a higher incidence of drug-related serious adverse events compared with JMDB patients (median 6 cycles of pemetrexed–cisplatin) (10.6% versus 2.9%); grade 3/4 fatigue and renal toxicity were also higher in the pemetrexed arm of PARAMOUNT. ConclusionsThe across-trial comparison of a relevant JMDB study population with the two arms of the PARAMOUNT study supported the efficacy of the pemetrexed continuation maintenance strategy and suggested the results are not influenced by limiting the pemetrexed–cisplatin induction treatment to four cycles. Although longer exposure to pemetrexed–cisplatin or maintenance pemetrexed increased some toxicities, the overall incidence remained low, underscoring the relative safety of these treatment regimens.

Final Efficacy and Safety Results of Pemetrexed Continuation Maintenance Therapy in the Elderly from the PARAMOUNT Phase III Study

The PARAMOUNT Phase III trial showed that maintenance pemetrexed after pemetrexed plus cisplatin induction was well tolerated and effective for patients with advanced nonsquamous non-small-cell lung cancer. Approximately 17% of patients receiving maintenance therapy in this study were 70 years of age or older. Here we report efficacy and safety results from the PARAMOUNT study for elderly (≥70 years) and non-elderly (<70 years) patients. Final efficacy and safety data from the PARAMOUNT study were analyzed post hoc using subgroup analyses for elderly and non-elderly patients. The median age was 73 years in the elderly subgroup (n = 92) and 60 years in the non-elderly subgroup (n = 447). Subgroups had similar baseline characteristics, except for a higher percentage of males and patients with a performance status of one in the elderly subgroup. For elderly patients, the median PFS was 6.4 months for pemetrexed and 3.0 months for placebo; the median OS was 13.7 months for pemetrexed and 12.1 months for placebo. For non-elderly patients, the median PFS was 4.0 months for pemetrexed and 2.8 months for placebo; the median OS was 13.9 months for pemetrexed and 10.8 months for placebo. Elderly patients experienced similar levels of low-grade toxicities, but had a higher percentage of grade 3/4 anemia and neutropenia than non-elderly patients, although importantly, this did not translate into increased febrile neutropenia. Continuation maintenance pemetrexed had comparable survival and toxicity profiles in the elderly and non-elderly subgroups. However, grade 3/4 anemia and neutropenia were numerically higher for elderly patients.

PARAMOUNT: Descriptive Subgroup Analyses of Final Overall Survival for the Phase III Study of Maintenance Pemetrexed versus Placebo Following Induction Treatment with Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non–Small-Cell Lung Cancer

Introduction:The PARAMOUNT phase III trial demonstrated that pemetrexed continuation maintenance significantly reduced the risk of disease progression (hazard ratio = 0.62) and death (hazard ratio = 0.78) versus placebo in patients with advanced nonsquamous non–small-cell lung cancer. To further understand the survival data, descriptive subgroup analyses were undertaken.Methods:Nine hundred thirty-nine patients received induction therapy (four 21-day cycles pemetrexed 500 mg/m2 and cisplatin 75 mg/m2), after which 539 nonprogressing patients with an Eastern Cooperative Oncology Group performance status (PS) of 0/1 were randomized (2:1) to maintenance pemetrexed (500 mg/m2) cycles or placebo until disease progression.Results:Baseline characteristics of patients surviving for longer periods were comparable to patients surviving shorter periods, suggesting overall survival (OS) benefit for all subgroups of patients on maintenance therapy. An examination of type and severity of induction adverse events also found no association with survival duration. Response to induction (tumor response versus stable disease) was not determinate of pemetrexed maintenance OS outcome as assessed by waterfall plot and scattergrams and by the distribution of patients among various OS intervals. The length of the interval before beginning maintenance therapy (<7 days versus ≥7/≤30 days) also did not impact the survival results. PS, a known prognostic factor, was the only baseline characteristic associated with improved OS; however, both PS 0 and PS 1 patients exhibited a survival benefit from pemetrexed maintenance.Conclusions:In PARAMOUNT, the OS benefit was seen across all subgroups. Other than PS, no baseline or clinical parameter clearly identified a subgroup more likely to benefit. Maintenance treatment decisions should be made on an individual basis.

Hypofractionated Stereotactic Radiotherapy for Orbital Metastases: A Case Report and Review of Literature

Objective: To evaluate the efficacy and clinical outcome of hypofractionated stereotactic radiotherapy (HSRT) in non-small-cell lung cancer (NSCLC) cancer patients with orbital metastasis. Case report: A 61-year-old man was admitted to the hospital referring right ptosis and dry hacking cough. HSRT was performed for the orbital metastasis followed by chemotherapy with cisplatin (60 mg/m2) and pemetrexed (500 mg/m2) on day 1 every 21 days for 4 cycles and maintenance pemetrexed (500 mg/m2) on day 1 every 21 days. Control TC scan revealed a complete response of the orbital mass. Conclusion: HSRT should be considered a valid therapeutic alternative in the management of selected patient with orbital metastases.

Pemetrexed and carboplatin followed by pemetrexed maintenance therapy in chemo-naïve patients with advanced nonsquamous non-small-cell lung cancer

This study prospectively evaluated the efficacy and safety of pemetrexed and carboplatin followed by maintenance pemetrexed in chemo-naïve patients with advanced nonsquamous non-small cell lung cancer (NSCLC). A total of 109 patients received pemetrexed (500 mg/m(2)) and carboplatin (area under the curve = 6 mg/mL·min) every 21 days. For patients without disease progression after 4 cycles, pemetrexed was continued until disease progression or unacceptable toxicity. Pre-planned subgroup analysis results based on the presence of epidermal growth factor receptor (EGFR) mutations are also presented. The median number of treatment cycles was 5 (range: 1-30) in the entire study period. Most of the grade ≥ 3 toxicities observed were hematologic in nature, with no increase in the relative incidence associated with continuation maintenance therapy with pemetrexed. Among the 106 total patients assessable for efficacy, the objective response rate was 35.8 %, median progression free survival (PFS) 5.7 months, and median overall survival (OS) 20.2 months. Sixty patients received maintenance pemetrexed (median: 4 cycles, range: 1-26 cycles); median PFS from the beginning of induction treatment was 7.5 months. From the subgroup analysis for EGFR mutation status, the median OS of EGFR wild-type patients (n=61) was 20.2 months. Pemetrexed/carboplatin followed by pemetrexed was well tolerated and active for front-line treatment of advanced nonsquamous NSCLC. Encouraging survival outcomes were observed even in EGFR-wild type patients.

PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non–Small-Cell Lung Cancer

In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data. In all, 939 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m(2) on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498). The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients. Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy.

Identifying the target NSCLC patient for maintenance therapy: an analysis from a placebo-controlled, phase III trial of maintenance pemetrexed (H3E-MC-JMEN)

BackgroundThis was a post hoc analysis of patients with non-squamous histology from a phase III maintenance pemetrexed study in advanced non-small cell lung cancer (NSCLC). Patients and methodsThe six symptom items' [average symptom burden index (ASBI)] mean at baseline was calculated using the lung cancer symptom scale (LCSS). Low and high symptom burden (LSB, ASBI < 25; HSB, ASBI ≥ 25) and performance status (PS: 0, 1) subgroups were analyzed for treatment effect on progression-free survival (PFS) and overall survival (OS) using the Cox proportional hazard models adjusted for demographic/clinical factors. ResultsSignificantly longer PFS and OS for pemetrexed versus placebo occurred in LSB patients [PFS: median 5.1 versus 2.4 months, hazard ratio (HR) 0.49, P < 0.0001; OS: median 17.5 versus 11.0 months, HR 0.63, P = 0.0012] and PS 0 patients (PFS: median 5.5 versus 1.7 months, HR 0.36, P < 0.0001; OS: median 17.7 versus 10.3 months, HR 0.54, P = 0.0019). Significantly longer PFS, but not OS, occurred in HSB patients (median 3.7 versus 2.8 months, HR 0.50, P = 0.0033) and PS 1 patients (median 4.4 versus 2.8 months, HR 0.60, P = 0.0002). ConclusionsASBI and PS are associated with survival for non-squamous NSCLC patients, suggesting that maintenance pemetrexed is useful for LSB or PS 0 patients following induction.

Randomized, open-label, phase III study of pemetrexed plus carboplatin followed by maintenance pemetrexed (Arm A) versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab (Arm B) in patients with advanced nonsquamous (NS) non-small cell lung cancer (NSCLC).

LBA8003 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.

First-line chemotherapy (CT) with pemetrexed (PEM) + cisplatin (CIS) + bevacuzimab (BEV) followed by maintenance PEM+BEV for advanced nonsquamous non-small cell lung cancer (NS-NSCLC): Final results of a single-arm phase II study.

e19148 Background: 1st line PEM+CIS induction CT followed by PEM maintenance and 1st line BEV-based CT followed by BEV maintenance offer clinical benefit (PFS, OS) in NS-NSCLC. This study explored efficacy and safety of 1st line induction PEM+CIS+BEV followed by maintenance PEM+BEV. Methods: Pts with advanced NS-NSCLC and ECOG 0-1 were planned to receive 4 cycles PEM 500 mg/m2, CIS 75 mg/m2, BEV 7.5 mg/kg, q3w. In absence of PD and with ECOG 0-1, pts could continue on PEM+BEV until PD or unacceptable toxicity. All pts received vitamin supplementation as per PEM label. Primary endpoint was PFS; secondary were OS, response rate, toxicity. Results: 109 pts were enrolled in 5 countries. Characteristics: median age 61 yrs, males/females 59/41%, ECOG 0/1 54/46%, IIIB/IV 9/91%, adenocarcinoma 91%. 72 pts (66%) had maintenance CT. Overall median (max) no of cycles were 6 (34) for PEM+BEV and 2 (4) for CIS. Median PFS was 6.9 m (90% CI 5.7, 8.3). The table gives efficacy and G3/4 AE data. 2 pts died from study-drug related toxicity (GI hemorrhage, pneumonia aspiration; during induction). Conclusions: In this study of PEM+CIS+BEV induction followed by PEM+BEV maintenance median PFS was 6.9 m. Main G3/4 toxicities included neutropenia and fatigue, hypertension was less common. Clinical trial information: NCT01004250. [Table: see text]

Effect of maintenance bevacizumab (Bev) plus pemetrexed (Pem) after first-line cisplatin/Pem/Bev in advanced nonsquamous non-small cell lung cancer (nsNSCLC) on overall survival (OS) of patients (pts) on the AVAPERL (MO22089) phase III randomized trial.

8014 Background: Maintenance monotherapy has been associated with improved survival for NSCLC pts. AVAPERL was designed to evaluate the safety and efficacy of bevacizumab with or without pemetrexed as continuation maintenance treatment and demonstrated improved progression-free survival (PFS) (Barlesi, JCO in press). Methods: Pts with advanced nsNSCLC received first-line Bev (7.5 mg/kg), cisplatin (75 mg/m2), and Pem (500 mg/m2) every 3 weeks (q3w) for 4 cycles. Those non progressing were randomized to maintenance Bev (7.5 mg/kg) +/-Pem (500 mg/m2) q3w until progressive disease or unacceptable toxicity. The primary end point (PFS) was met. An independent update analysis has been conducted to assess OS. Results: A total of 376 pts receive induction treatment; 125 and 128 were randomized to the Bev-alone and Bev+Pem arms, respectively. Induction therapy resulted in confirmed disease control in 71.9% of pts. After a median follow-up of 14.8 months, PFS for the Bev+Pem arm was significantly improved both from induction (10.2 v 6.6 m, HR 0.58 [0.45-0.76], p&lt;.0001) and randomization (7.4 v 3.7 m, HR 0.57 [0.44-0.75], p&lt;.0001). With 58% of events, OS for the Bev+Pem arm was also improved both from induction (19.8 v 15.9 m, HR 0.88 [0.64-1.22], p=.32) and randomization (17.1 v 13.2 m, HR 0.87 [0.63-1.21], p=.29). The PFS and OS improvements were comparable across age, PS, smoking status, and response to induction (SD vPR/CR) subgroups. No new safety signal was observed during this updated analysis. Conclusions: Continuation maintenance with Bev+Pem in an unselected population of nsNSCLC pts who had achieved disease control after induction was associated with an increase by almost 4 months in OS benefit over standard Bev alone. Clinical trial information: NCT00961415.

A randomized phase II trial comparing continuation maintenance therapy with pemetrexed and switch maintenance therapy with docetaxel after first-line therapy with carboplatin and pemetrexed in patients with advanced nonsquamous non-small cell lung cancer.

8038 Background: Emerging evidence suggests that maintenance chemotherapy could prolong survival in patients with advanced non-small-cell lung cancer (NSCLC), whereas the optimal treatment strategy remains controversial. Methods: We conducted a randomized phase II study to compare the efficacy and safety of continuation maintenance with pemetrexed (500 mg/m2) and switch maintenance with docetaxel (60 mg/m2) in patients with non-squamous NSCLC who achieved disease control after first-line chemotherapy with four cycles of carboplatin (AUC 6) and pemetrexed (500 mg/m2). Results: Eighty-five patients participated in the study, and 26 and 25 patients were randomized to the pemetrexed and the docetaxel maintenance therapies, respectively. The docetaxel group showed a trend toward longer progression-free survival (median 8.2 months, 95% CI; 3.9-12.2 months) compared with the pemetrexed group (median 4.1 months, 95% CI; 3.0-6.1 months), but not significantly (log-rank p=0.084). Grade 3/4 hematologic toxicity was significantly more frequent in the docetaxel group (80%) than the pemetrexed group (20%, p&lt;0.0001). Conclusions: Continuation maintenance with pemetrexed after induction therapy with carboplatin and pemetrexed may be an efficacious treatment with less toxicity. In contrast, switch maintenance with docetaxel frequently causes severe hematologic toxicity but may be more efficacious. Further studies are warranted to evaluate the risks and benefits of maintenance therapies. Clinical trial information: 000004075.

Cost-Effectiveness of Continuation Maintenance Pemetrexed After Cisplatin and Pemetrexed Chemotherapy for Advanced Nonsquamous Non–Small-Cell Lung Cancer: Estimates From the Perspective of the Chinese Health Care System

BackgroundContinuation maintenance treatment with pemetrexed is approved by current clinical guidelines as a category 2A recommendation after induction therapy with cisplatin and pemetrexed chemotherapy (CP strategy) for patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). However, the cost-effectiveness of the treatment remains unclear. ObjectiveWe completed a trial-based assessment, from the perspective of the Chinese health care system, of the cost-effectiveness of maintenance pemetrexed treatment after a CP strategy for patients with advanced nonsquamous NSCLC. MethodsA Markov model was developed to estimate costs and benefits. It was based on a clinical trial that compared continuation maintenance pemetrexed therapy plus best supportive care (BSC) versus placebo plus BSC after a CP strategy for advanced nonsquamous NSCLC. Sensitivity analyses were conducted to assess the stability of the model. ResultsThe model base case analysis suggested that continuation maintenance pemetrexed therapy after a CP strategy would increase benefits in a 1-, 2-, 5-, or 10-year time horizon, with incremental costs of $183,589.06, $126,353.16, $124,766.68, and $124,793.12 per quality-adjusted life-year gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was the utility of the progression-free survival state, followed by proportion of patients with postdiscontinuation therapy in both arms, proportion of BSC costs for PFS versus progressed survival state, and cost of pemetrexed. Probabilistic sensitivity analysis indicated that the cost-effective probability of adding continuation maintenance pemetrexed therapy to BSC was zero. One-way and probabilistic sensitivity analyses revealed that the Markov model was robust. ConclusionsContinuation maintenance of pemetrexed after a CP strategy for patients with advanced nonsquamous NSCLC is not cost-effective based on a recent clinical trial. Decreasing the price or adjusting the dosage of pemetrexed may be a better option for meeting the treatment demands of Chinese patients ClinicalTrials.gov identifier: NCT00789373.

Safety, Resource Use, and Quality of Life in Paramount: A Phase III Study of Maintenance Pemetrexed Versus Placebo after Induction Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non–Small-Cell Lung Cancer

In a phase III, randomized, double-blind study (PARAMOUNT), maintenance pemetrexed demonstrated significant benefit in advanced non-small-cell lung cancer (NSCLC). We present safety, resource use, and quality of life (QoL) results. After four 21-day cycles of pemetrexed-cisplatin (N = 939), patients with advanced nonsquamous NSCLC, whose disease had not progressed and who had a performance status of 0/1, were randomized 2:1 (N = 539) to maintenance pemetrexed 500 mg/m plus best supportive care or placebo plus best supportive care every 21 days until disease progression or unacceptable toxicity. QoL was measured using the EuroQol 5-dimensional questionnaire (EQ-5D). Frequently reported grade 3 to 4 drug-related toxicities with maintenance pemetrexed versus placebo were anemia (4.5% versus 0.6%; p = 0.016), fatigue (4.2% versus 0.6%; p = 0.016), and neutropenia (3.6% versus 0.0%; p < 0.006). No significant differences in drug-related grade 3 to 5 toxicities were observed with long-term pemetrexed exposure (>6 cycles), except grade 3 to 4 neutropenia, which did not result in increased infections. Patients on maintenance pemetrexed required more transfusions (13.4% versus 5.0%; p = 0.003), granulocyte colony- or granulocyte-macrophage colony-stimulating factors (5.3% versus 0.0%; p <0.001), anti-infectives (25.3% versus 16.7%; p = 0.028), and hospitalizations because of study drug (8.4% versus 3.3%, p = 0.028) than placebo-treated patients did. No significant treatment-by-time interactions, overall treatment differences, or clinically relevant changes from baseline were observed in EQ-5D scores during treatment. Long-term use of continuation maintenance pemetrexed was well tolerated; resource use was low, corresponding with known pemetrexed toxicities. The EQ-5D results demonstrate that patients tolerate long-term maintenance pemetrexed without worsening QoL.