SATURN: A double-blind, randomized, phase III study of maintenance erlotinib versus placebo following nonprogression with first-line platinum-based chemotherapy in patients with advanced NSCLC

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8001-8001 ◽  
Author(s):  
F. Cappuzzo ◽  
T. Ciuleanu ◽  
L. Stelmakh ◽  
S. Cicenas ◽  
A. Szczesna ◽  
...  
Keyword(s):  
Disease Control ◽  
Primary Endpoint ◽  
Advanced Nsclc ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Double Blind ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

8001 Background: Erlotinib (E), a small-molecule EGFR TKI, is proven to extend survival versus placebo (P) in 2nd/3rd-line advanced NSCLC. The phase III SATURN study (BO18192) was initiated to evaluate E as maintenance therapy after standard 1st-line platinum-based chemotherapy (CT) in advanced NSCLC. Methods: Patients with no evidence of disease progression after 4 cycles of CT were randomized to receive either E 150 mg/day or P until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) in all patients and the co-primary endpoint was PFS in EGFR immunohistochemistry-positive (IHC+) patients. Results: A total of 1,949 patients entered the CT phase, of whom 889 were randomized to E (n=438) or P (n=451). Median age was 60 years for both arms. Baseline characteristics for E and P arms (%): male/female: 73/27 and 75/25; adenocarcinoma + BAC/squamous-cell/other: 47/38/15 and 44/43/13; stage IIIB/IV: 26/74 and 24/76; Caucasian/Asian/other: 84/14/2 and 83/15/2; ECOG PS 0/1: 31/69 and 32/68; current/former/never smoker: 55/28/18 and 56/27/17. PFS (by investigator assessment; confirmed by independent review) was significantly prolonged with E versus P in all patients (HR 0.71 [95% CI 0.62–0.82]; p<.0001) and in EGFR IHC+ patients (HR 0.69 [95% CI 0.58–0.82]; p<.0001). Subgroup analyses will be reported. Response rate was 12% with E versus 5% with P. Disease control rate (complete response + partial response + stable disease >12 wks) was 40.8% with E versus 27.4% with P (p<.0001). OS data are not yet mature. E was well tolerated: the majority of treatment-related adverse events (AEs) were grade 1/2. AEs reported in ≥10% of all patients were rash (60% with E versus 9% with P) and diarrhea (20% with E versus 5% with P); again, most were grade 1/2. Only 2.3% of patients receiving E had a serious treatment-related AE and 2.8% withdrew due to a treatment-related AE. Conclusions: The SATURN study met its primary and co-primary endpoints with high statistical significance. Erlotinib in the 1st-line maintenance setting is well tolerated, and significantly improves disease control and delays progression versus placebo across patient subgroups. [Table: see text]

Third-line treatment: A randomized, double-blind, placebo-controlled phase III ALTER-0303 study—Efficacy and safety of anlotinib treatment in patients with refractory advanced NSCLC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9053-9053 ◽  
Author(s):  
Baihui Han ◽  
Kai Li ◽  
Qiming Wang ◽  
Yizhuo Zhao ◽  
Li Zhang ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Advanced Nsclc ◽  
Phase Iii ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Third Line ◽  
Ecog Ps ◽  
Third Line Treatment

9053 Background: Anlotinib hydrochloride, an oral TKI targeting VEGFR, FGFR, PDGFR and c-Kit, showed promising efficacy in PhaseⅡstudy. Here, we evaluated the efficacy and safety of anlotinib as third-line treatment for advanced NSCLC, a randomized, double-blind, placebo-controlled Phase Ⅲtrial (ALTER-0303). Methods: Eligible ⅢB/Ⅳ NSCLC pts who progressed after at least 2 lines of prior therapies were randomized 2:1 to receive anlotinib or placebo (12 mg QD from day 1 to 14 of a 21-day cycle) till progression or intolerable toxicity. Enrolled pts harboring EGFR or ALK mutations must had failed in previous match-targeted therapies. The primary endpoint is OS; secondary endpoint includes PFS, DCR and ORR. Results: As of Aug 2016, total of 437 pts from 31 sites were randomized. The baseline characteristics of Anlotinib arm (N=294) and placebo arm (N=143) were well balanced in the age, gender, ECOG PS and gene states. With 292 OS events (66.82%), significant superiorities in OS, PFS, DCR and ORR were observed in Anlotinib arm according to investigator-assessed results. Grade ≥ 3 treatment-related AEs were hypertension, dermal toxicity and hypertriglyceridemia. There was no treatment–related death in either arm. (Data presented in the Table.) Conclusions: ALTER-0303 trial met its primary endpoint. Anlotinib significantly improved OS and PFS in advanced NSCLC with a manageable safety profile. The results strongly suggest that anlotinib should be considered as a candidate for the third-line treatment or beyond in advanced NSCLC. Clinical trial information: NCT02388919. [Table: see text]

RAISE: A randomized, double-blind, multicenter phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab (RAM) or placebo (PBO) in patients (pts) with metastatic colorectal carcinoma (CRC) progressive during or following first-line combination therapy with bevacizumab (bev), oxaliplatin (ox), and a fluoropyrimidine (fp).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
Josep Tabernero ◽  
Allen Lee Cohn ◽  
Radka Obermannova ◽  
Gyorgy Bodoky ◽  
Rocio Garcia-Carbonero ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Statistical Significance ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Double Blind ◽  
Ecog Ps

512 Background: Angiogenesis is an important therapeutic target in CRC; VEGF plays a key role in angiogenesis. RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The RAISE study evaluated the efficacy and safety of adding RAM to standard second-line treatment FOLFIRI. Methods: Eligible pts with mCRC who progressed on or after first-line combination therapy with bev, ox, and fp, had an ECOG PS of 0 or 1, and adequate organ function were randomized 1:1 (stratified by region, KRAS mutation status, and time to progressive disease [PD] after beginning first-line treatment) to receive RAM (8 mg/kg IV) plus FOLFIRI or PBO plus FOLFIRI every 2 weeks until PD, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Planned sample size of 1,050 pts ensured 85% power to demonstrate statistical significance at an overall two-sided alpha of 0.05, assuming a hazard ratio (HR) of 0.8. Results: Between Dec 2010 and Aug 2013, 1,072 eligible pts were randomized (RAM 536; PBO 536). Baseline pt characteristics were similar between treatment arms. The OS HR was 0.84 (95% CI: 0.73, 0.98; log-rank p=0.0219). Median OS was 13.3months (m) for RAM vs 11.7m for PBO. The PFS HR was 0.79 (95% CI: 0.70, 0.90; log-rank p = 0.0005). Median PFS with RAM was 5.7m and 4.5m for PBO. ORR was 13.4% RAM; 12.5% PBO (p = 0.6336). Subgroup results were consistent with the OS and PFS results. Grade ≥3 adverse events (AEs) occurring in >5% of pts in RAM+FOLFIRI were: neutropenia (RAM 38.4% vs PBO 23.3% ), hypertension (11.2% vs 2.8%), diarrhea (10.8% vs 9.7%), and fatigue (11.5% vs 7.8%). Conclusions: RAISE met its primary end-point, demonstrating a statistically significant improvement in OS for RAM and FOLFIRI vs PBO and FOLFIRI in second-line mCRC pts. Benefits were similar across important clinical subgroups and no unexpected AEs were identified. Clinical trial information: NCT01183780.

ZD6474 versus gefitinib in patients with advanced NSCLC: Final results from a two-part, double-blind, randomized phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7000-7000 ◽  
Author(s):  
R. B. Natale ◽  
D. Bodkin ◽  
R. Govindan ◽  
B. Sleckman ◽  
N. Rizvi ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Disease Control ◽  
Advanced Nsclc ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Double Blind ◽  
Significant Prolongation ◽  
Platinum Based Chemotherapy ◽  
Grade 3

7000 Background: ZD6474 is a once-daily oral agent that targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinase activity. The efficacy and safety of ZD6474 was compared with that of gefitinib, an EGFR tyrosine kinase inhibitor. Methods: Patients with locally advanced or metastatic (stage IIIB/IV) non-small-cell lung cancer (NSCLC), after failure of 1st-line ± 2nd-line platinum-based chemotherapy because of toxicity or tumor progression, received daily oral doses of ZD6474 (300 mg) or gefitinib (250 mg) until disease progression or evidence of toxicity (Part A). After a washout period of 4 weeks, eligible patients had the option to switch to the alternative treatment, which continued until a withdrawal criterion was met (Part B). The dual primary objectives in Part A were assessments of progression-free survival (PFS) and safety/tolerability. All adverse events were assessed using Common Toxicity Criteria (CTC) version 2.0. Results: A total of 168 patients received initial treatment with ZD6474 (n=83) or gefitinib (n=85). In Part A, median PFS was 11.0 weeks for ZD6474 and 8.1 weeks for gefitinib (hazard ratio [95% CI] = 0.69 [0.50–0.96], P=0.025); disease control >8 weeks was achieved in 37/83 (45%) patients receiving ZD6474 and in 29/85 (34%) receiving gefitinib. The adverse event profile of ZD6474 in Part A was similar to that seen in previous trials, and included diarrhea (CTC grade 3/4, 8.4%), rash (CTC grade 3/4, 4.8%) and asymptomatic QTc prolongation (all CTC grade 1, 20.5%). There were no unexpected safety findings with gefitinib-treated patients. In Part B, disease control >8 weeks was achieved in 16/37 patients who switched to ZD6474 (from gefitinib) and in 7/29 who switched to gefitinib (from ZD6474). Overall survival was not significantly different between patients initially randomized to either ZD6474 or gefitinib (median 6.1 and 7.4 months, respectively). Conclusions: This study achieved its primary efficacy objective, with ZD6474 demonstrating a significant prolongation of PFS versus gefitinib. These data support further confirmatory trials of ZD6474 in patients with advanced NSCLC. [Table: see text]

Randomized phase III trial of imatinib (IM) rechallenge versus placebo (PL) in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) after failure of at least both IM and sunitinib (SU): RIGHT study.

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA10502-LBA10502 ◽  
Author(s):  
Yoon-Koo Kang ◽  
Min-Hee Ryu ◽  
Baek-Yeol Ryoo ◽  
Hyun Jin Kim ◽  
Jong Jin Lee ◽  
...  
Keyword(s):  
Disease Control ◽  
Primary Endpoint ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Advanced Gist

LBA10502 Background: To palliate and prolong disease control after failure of all available treatment in advanced GIST, resumption of IM dosing has been commonly practiced based on evidence of rapid GIST progression after discontinuation of all TKIs. We evaluated the efficacy of IM rechallenge in pts with advanced GIST following failure of all TKIs. Methods: Eligible pts had metastatic and/or unresectable GIST with prior benefit from first-line IM (defined as disease control for > 6 months), progressive disease (PD) on first-line IM, PD on or intolerance to SU, and ECOG performance status 0-3. Pts were randomized 1:1 to receive best supportive care with either IM 400 mg po once daily or PL. At the time of PD, pts were unblinded and allowed to cross-over to open-label IM. The primary endpoint was progression-free survival (PFS) determined by blinded external radiology review according to RECIST v1.0. Secondary endpoints included overall survival (OS), time to progression, disease control rate (DCR) at 12 weeks, and safety. Results: Between July 2010 and January 2013, 81 pts were randomized (IM: 41, PL: 40) at a single Korean center. All baseline characteristics were balanced between the arms and 40% of pts received ≥ 3 prior TKIs. The planned final analysis in March 2013 demonstrated that the primary endpoint was met, with significantly greater PFS for pts randomized to IM vs. PL : 1.8 vs. 0.9 months, respectively (p=0.002), hazard ratio (HR) 0.45 (95% CI, 0.27-0.76). DCR at 12 weeks was 32% for IM vs. 5% for PL (p=0.003). With 92.5 % of PL pts rapidly crossing over to IM, median OS was 8.2 months for IM vs. 7.5 months for PL (HR of 0.99, p=0.982). The most common treatment-emergent AEs (> grade 3) during double-blind period in the IM arm included anemia (29%), fatigue (10%), and hyperbilirubinemia (7%). Conclusions: Rechallenge of IM significantly improves PFS and DCR in pts with advanced GIST after failure of at least IM and SU, likely by continuous kinase inhibition of the bulk of disease clones which retain IM sensitivity. However, TKI-resistant clones continue to progress leading to relatively brief duration of benefit. Clinical trial information: NCT01151852.

S0536: Carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC): A SWOG phase II study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8015-8015 ◽  
Author(s):  
D. Gandara ◽  
E. S. Kim ◽  
R. S. Herbst ◽  
J. Moon ◽  
M. W. Redman ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Advanced Nsclc ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Phase Iii ◽  
Platinum Based Chemotherapy ◽  
Treatment Naïve ◽  
Secondary Endpoints ◽  
Lung Hemorrhage

8015 Background: Cetuximab (CX) plus platinum-based chemotherapy improves overall survival (OS) in advanced NSCLC (FLEX). SWOG previously showed that EGFR FISH is associated with efficacy outcomes in patients (pts) receiving CB/P/CX (S0342). Bevacizumab (B) plus chemotherapy also increases survival (E4599) in eligible pts. Given the biologic rationale for combining EGFR and VEGFR targeted agents, S0536 investigated the safety and efficacy of carboplatin (CB), paclitaxel (P) and CX plus B. Methods: Eligibility: treatment-naïve advanced stage non-squamous cell NSCLC, no requirement for EGFR positivity, PS 0–1, no brain metastases or hemoptysis. Treatment: CB AUC 6, P 200 mg/m2, B 15 mg/kg IV day 1 every 3 weeks, CX 400 mg/m2 day 1 then 250 mg/m2 weekly for up to 6 cycles; then B 15 mg/kg every 3 weeks and CX 250 mg/m2 weekly until progression. Primary endpoint: feasibility defined by the frequency and severity of ≥grade 4 hemorrhagic toxicities. Secondary endpoints: response rate, progression-free survival (PFS), OS and toxicity. Results: 110 pts enrolled from August 2006 to September 2007; 104 assessable. Pt characteristics: median age 64 years (42–78), Male/Female 52/52, PS 0/1 43/61, stage IIIB/IV 9/95, adenocarcinoma: 81, current/former smoker: 82. Overall toxicities were acceptable and comparable to S0342 and E4599. Primary endpoint was met: grade ≥4 hemorrhage: 2% (95% CI: 0–7%). There were 4 treatment-related deaths: lung hemorrhage (2), infection (1), unknown (1). Partial response (PR): 51/95 assessable (54%; 43%-64%); Stable disease (SD): 22/95 (23%). Disease control rate (PR+SD): 77%. With median follow up of 15 months (mos), PFS is 7 mos (18 pts remain progression-free) and OS is 14 mos. 1 year survival is 57% (47–67%). EGFR IHC by H score (>0 vs 0) showed a nonsignificant trend toward improved survival: 15 vs 11 mos (p=0.14). Conclusions: CB/P, CX plus B demonstrates safety, tolerability and efficacy in advanced NSCLC and is the most active regimen studied to date in SWOG. Additional S0536 biomarker studies including EGFR FISH will be presented. S0819, a Phase III trial of CB/P ± CX (plus B in eligible pts) is under development and is designed to validate EGFR FISH as a predictive biomarker. [Table: see text]

Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION primary analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5545-5545
Author(s):  
Andres Poveda ◽  
Stephanie Lheureux ◽  
Nicoletta Colombo ◽  
David Cibula ◽  
Kristina Lindemann ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Progression Free Survival ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Phase Iii ◽  
Primary Analysis ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Phase Iiib ◽  
Grade 3

5545 Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including non-BRCAm pts. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et al Lancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 prior lines of platinum-based chemotherapy (PBC), we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and were in complete response (CR) or partial response (PR) to PBC. Pts received maintenance olaparib (tablets; 300 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). Secondary endpoints included PFS by homologous recombination deficiency (HRD) and somatic BRCA mutation (sBRCAm) status determined by central Myriad tumor and germline testing; and time to first subsequent treatment (TFST). The primary analysis was planned for 18 months (mo) after the last patient was enrolled. Results: 279 pts were enrolled from 17 countries (mean age: 64 years); 253 pts (90.7%) were confirmed non-gBRCAm. At data cut-off (Oct 2, 2020), median PFS was 9.2 mo (95% CI 7.6–10.9), with 210 PFS events (75.3% maturity). 65.3%, 38.5% and 24.3% of pts were progression-free (PF) at 6, 12 and 18 mo, respectively. The Table shows PFS in key subgroups. Median TFST was 13.9 mo (95% CI 11.5–16.4). Median exposure to olaparib was 9.4 mo (range 0.0–31.9). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 29.0% of pts and serious TEAEs in 19.7% of pts. TEAEs led to dose interruption, dose reduction and treatment discontinuation in 47.0%, 22.6% and 7.5% of pts, respectively. Conclusions: Our findings support the use of olaparib maintenance therapy in non-gBRCAm PSR OC pts, consistent with our interim analysis and previous trials in this setting. Clinical trial information: NCT03402841. [Table: see text]

Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial

2020 ◽  
Vol 38 (3) ◽  
pp. 193-202 ◽  
Author(s):  
Richard S. Finn ◽  
Baek-Yeol Ryoo ◽  
Philippe Merle ◽  
Masatoshi Kudo ◽  
Mohamed Bouattour ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Interim Analysis ◽  
Statistical Significance ◽  
Study Drug ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Double Blind ◽  
Previously Treated

PURPOSE Pembrolizumab demonstrated antitumor activity and safety in the phase II KEYNOTE-224 trial in previously treated patients with advanced hepatocellular carcinoma (HCC). KEYNOTE-240 evaluated the efficacy and safety of pembrolizumab in this population. PATIENTS AND METHODS This randomized, double-blind, phase III study was conducted at 119 medical centers in 27 countries. Eligible patients with advanced HCC, previously treated with sorafenib, were randomly assigned at a two-to-one ratio to receive pembrolizumab plus best supportive care (BSC) or placebo plus BSC. Primary end points were overall survival (OS) and progression-free survival (PFS; one-sided significance thresholds, P = .0174 [final analysis] and P = .002 [first interim analysis], respectively). Safety was assessed in all patients who received ≥ 1 dose of study drug. RESULTS Between May 31, 2016, and November 23, 2017, 413 patients were randomly assigned. As of January 2, 2019, median follow-up was 13.8 months for pembrolizumab and 10.6 months for placebo. Median OS was 13.9 months (95% CI, 11.6 to 16.0 months) for pembrolizumab versus 10.6 months (95% CI, 8.3 to 13.5 months) for placebo (hazard ratio [HR], 0.781; 95% CI, 0.611 to 0.998; P = .0238). Median PFS for pembrolizumab was 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 2.5 to 4.1 months) for placebo at the first interim analysis (HR, 0.775; 95% CI, 0.609 to 0.987; P = .0186) and 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 1.6 to 3.0 months) at final analysis (HR, 0.718; 95% CI, 0.570 to 0.904; P = .0022). Grade 3 or higher adverse events occurred in 147 (52.7%) and 62 patients (46.3%) for pembrolizumab versus placebo; those that were treatment related occurred in 52 (18.6%) and 10 patients (7.5%), respectively. No hepatitis C or B flares were identified. CONCLUSION In this study, OS and PFS did not reach statistical significance per specified criteria. The results are consistent with those of KEYNOTE-224, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population.

Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA10008-LBA10008 ◽  
Author(s):  
George D. Demetri ◽  
Peter Reichardt ◽  
Yoon-Koo Kang ◽  
Jean-Yves Blay ◽  
Heikki Joensuu ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind Study ◽  
Open Label ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Multikinase Inhibitor

LBA10008 Background: Oral multikinase inhibitor regorafenib (REG) demonstrated substantial activity in a phase II trial in pts with GIST after failure of both IM and SU (J Clin Oncol. 2011; 29:606s; abstr 10007). This phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of REG for this unmet clinical need. Methods: Eligible pts had metastatic and/or unresectable GIST, objective failure of both prior IM and SU (progressive disease [PD] on, or intolerance to, IM and PD on SU), ≥1 measurable lesion, ECOG performance status 0 or 1. Pts were randomized 2:1 to receive best supportive care plus either REG 160 mg po once daily (3 wks on/1 wk off) or placebo (PL). The primary endpoint was progression-free survival (PFS) (modified RECIST 1.1, independent central review). Secondary endpoints included overall survival (OS), disease control rate (DCR, defined as rate of partial response [PR] plus stable disease [SD] lasting for ≥12 wks), response rate and duration, safety and correlative genotype analyses. At time of PD, pts were eligible for unblinding and crossover to open-label REG. Results: Between Jan and Aug of 2011, 234 pts were screened; 199 were randomized (REG: 133, PL: 66). Pts were stratified at randomization according to number of prior systemic therapies and geographical region. Baseline characteristics were balanced between the two arms. The primary endpoint was met: median PFS was 4.8 months for REG vs. 0.9 months for PL. Hazard ratio for PFS was 0.27 (95% CI, 0.18-0.39), p<0.0001. PFS rates at 3 and 6 months were 60% and 38% for REG vs. 11% and 0% for PL. DCR was 53% (REG) vs. 9% (PL).The HR for OS was 0.77 (p=0.20) with 85% PL pts having crossed over to REG. The most common > grade 3 treatment-emergent AEs in the REG arm during double-blind study were hypertension (28%), hand-foot skin reaction (21%), and diarrhea (8%). Conclusions: This randomized trial demonstrated that REG significantly improved PFS and DCR in pts with advanced GIST after failure of at least prior IM and SU. REG was well tolerated, with AEs as expected for this class and manageable with dose modifications.

Randomized phase III trial of irinotecan plus cisplatin versus irinotecan alone after S-1 based chemotherapy failure for patients with advanced and recurrent gastric cancer (AGC) (TCOG GI-0801).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 61-61
Author(s):  
Ken Shimada ◽  
Katsuhiko Higuchi ◽  
Naoshi Hosaka ◽  
Eisaku Sasaki ◽  
Norisuke Nakayama ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Statistical Design ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
High Level ◽  
Ecog Ps ◽  
Line Chemotherapy

61 Background: S-1based chemotherapy is the standard first-line chemotherapy for AGC in Japan. Currently, there is no high level evidence established for second-line treatment. Irinotecan (CPT-11) plus cisplatin (CDDP) are active in AGC. The combination of these 2 agents is synergistic effect in preclinical and clinical studies. We conducted a phase III study of CPT-11 plus CDDP (CP) compared with CPT-11 alone (C) in patients with AGC refractory to S-1 based chemotherapy. Methods: Patients with previously treated with S-1-based chemotherapy for AGC, an ECOG PS of 0-1 and adequate organ functions were randomly assigned to receive either CPT-11 60 mg/m2 plus CDDP 30 mg/m2 on day 1 every 2 weeks or CPT-11 150mg/m2on day 1 every 2 weeks. The primary endpoint is progression free survival (PFS). The statistical design is based on superiority hypothesis; PFS is 110days in CP, 65days in C; two-sided α=0.05, 1-β=0.8; and planed accrual is 130 pts. Secondary endpoints include Overall Survival (OS), Time to Treatment Failure (TTF), Response Rate (RR), and safety. Results: From April 2008 to July 2011, 130 patients from 21 sites in Japan were randomized to CP (n=64) or C (n=66). Patient demographics were well balanced between the two groups. At the final analysis, total of 117 PFS events were observed. The primary endpoint was met. PFS for CP was superiority to C (median PFS, 4.17(95%CI 3.03-4.80) vs. 3.03(95%CI 2.20-3.33) months, respectively; HR=1.490(1.029-2.155), p=0.0324,). There were no significant differences in the TTF and RR (TTF was 3.4(95%CI 2.7-4.2) vs. 2.9(95%CI 2.2-3.3) months, RR was 21.9(95%CI 12.5-34.0) % vs. 16.4(95%CI 7.9-27.3) % with CP and C. OS is analyzing now. The most common grade 3/4 toxicities in CP/C (%) were neutropenia, 40.6/38.7; diarrhea, 1.6/7.9; anorexia, 4.7/11.1. Related adverse events were comparable with CP and C.Conclusions: CP has promising efficacy for the second-line chemotherapy compared with C for AGC.CP suggested to be one of the standard second-line chemotherapy regimen for AGC. Clinical trial information: 000001028.

REVEL: A randomized, double-blind, phase III study of docetaxel (DOC) and ramucirumab (RAM; IMC-1121B) versus DOC and placebo (PL) in the second-line treatment of stage IV non-small cell lung cancer (NSCLC) following disease progression after one prior platinum-based therapy.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA8006-LBA8006 ◽  
Author(s):  
Maurice Perol ◽  
Tudor-Eliade Ciuleanu ◽  
Oscar Arrieta ◽  
Kumar Prabhash ◽  
Konstantinos N. Syrigos ◽  
...  
Keyword(s):  
Disease Progression ◽  
Primary Endpoint ◽  
Objective Response ◽  
Pulmonary Hemorrhage ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Double Blind

LBA8006^ Background: RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The REVEL study evaluated the efficacy and safety of RAM+DOC vs. PL+DOC (DOC) in patients (pts) with stage IV nonsquamous (NSQ) and squamous (SQ) NSCLC after platinum-based therapy. Methods: Pts with NSQ and SQ stage IV NSCLC were randomized 1:1 (stratified by sex, region, ECOG PS, and prior maintenance therapy) to receive DOC 75 mg/m2 in combination with either RAM 10 mg/kg or PL on day 1 of a 21-day cycle until disease progression, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary efficacy endpoints included progression-free survival (PFS), and objective response rate (ORR). Results: Between Dec 2010 and Feb 2013, 1,253 pts (26.2% SQ) were randomized (RAM+DOC: 628; DOC: 625). Pt characteristics were balanced between arms. ORR was 22.9% for RAM+DOC and 13.6% for DOC (P<0.001). The hazard ratio (HR) for PFS was 0.762 (P<0.0001); median PFS was 4.5 months (m) for RAM+DOC vs. 3.0m for DOC. REVEL met its primary endpoint; the OS HR was 0.857 (95% CI 0.751, 0.98; P=0.0235); median OS was 10.5m for RAM+DOC vs. 9.1m for DOC. OS was longer for RAM+DOC in most pt subgroups, including SQ and NSQ histology. Grade ≥3 adverse events (AEs) occurring in >5% of pts on RAM+DOC were neutropenia (34.9% vs. 28.0%), febrile neutropenia (15.9% vs. 10.0%), fatigue (11.3% vs. 8.1%), leukopenia (8.5% vs. 7.6%), hypertension (5.4% vs. 1.9%), and pneumonia (5.1% vs. 5.8%). Grade 5 AEs were comparable between arms (5.4% vs. 5.8%), as was pulmonary hemorrhage (any grade; all pts: 2.1% vs. 1.6%; SQ pts: 3.8% vs. 2.4%). Conclusions: REVEL demonstrated a statistically significant improvement in ORR, PFS, and OS for RAM+DOC vs DOC in NSCLC pts with stage IV NSCLC as second-line treatment after platinum-based therapy. Benefits were similar in NSQ and SQ pts, and no unexpected AEs were identified. Clinical trial information: NCT01168973.

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