Randomized double-blind phase II study of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients (pts) with metastatic urothelial cancer (mUC): HCRN GU14-182.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4504-4504 ◽  
Author(s):  
Matt D. Galsky ◽  
Sumanta K. Pal ◽  
Amir Mortazavi ◽  
Matthew I. Milowsky ◽  
Saby George ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Maximum Efficiency ◽  
Double Blind ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Line Chemotherapy

4504 Background: Platinum-based chemotherapy for 1st-line treatment of pts with metastatic urothelial cancer (mUC) is typically administered for a fixed duration followed by observation until recurrence. PD-1 blockade with pembro improves survival of pts with mUC progressing despite platinum-based chemotherapy. We explored the potential benefit of earlier use of PD-1 blockade using a "switch maintenance" approach. Methods: Pts with mUC achieving at least stable disease after up to 8 cycles of 1st-line platinum-based chemotherapy were enrolled. Pts were randomized 1:1 to pembro 200 mg IV q3 weeks versus placebo for up to 24 months; pts progressing on placebo could cross over to pembro. Randomization was stratified based on pre-chemotherapy visceral metastases (Y/N) and response to 1st-line chemotherapy (CR/PR vs. SD). The primary objective was to determine the progression-free survival (PFS) as per irRECIST among pts treated with pembro versus placebo. Results: Between 12/2015 and 11/2018, 107 pts were randomized to placebo (n=52) versus pembro (n=55). The baseline pt characteristics are shown in the Table. Pts randomized to placebo and pembro received a median of 6 and 8 cycles, respectively. Excluding patients with baseline CRs, the objective response rate was 12% (5/42) on placebo and 22% (10/46) on pembro. Grade 3-4 treatment emergent adverse events occurred in 48% of pts on placebo and 56% on pembro. At a median follow-up of 14.7 months, 41 pts have died and 26/52 pts randomized to placebo have crossed over to pembro. PFS was significantly longer in patients randomized to pembro vs. placebo (Maximum Efficiency Robust Test p=0.036; log-rank p = 0.038). The 18-month restricted mean progression-free survival time was 5.6 months with placebo and 8.2 months with pembro (p=0.023). Conclusions: Switch maintenance pembro may “deepen” responses achieved with 1st-line chemotherapy. Switch maintenance pembro prolongs PFS in pts with mUC completing 1st-line platinum-based chemotherapy. Clinical trial information: NCT02500121. [Table: see text]

scholarly journals Randomized Double-Blind Phase II Study of Maintenance Pembrolizumab Versus Placebo After First-Line Chemotherapy in Patients With Metastatic Urothelial Cancer

2020 ◽  
Vol 38 (16) ◽  
pp. 1797-1806 ◽  
Author(s):  
Matthew D. Galsky ◽  
Amir Mortazavi ◽  
Matthew I. Milowsky ◽  
Saby George ◽  
Sumati Gupta ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stable Disease ◽  
Urothelial Cancer ◽  
Progression Free Survival ◽  
Maximum Efficiency ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

PURPOSE Platinum-based chemotherapy for first-line treatment of metastatic urothelial cancer is typically administered for a fixed duration followed by observation until progression. “Switch maintenance” therapy with PD-1 blockade at the time of chemotherapy cessation may be attractive for mechanistic and pragmatic reasons. PATIENTS AND METHODS Patients with metastatic urothelial cancer achieving at least stable disease on first-line platinum-based chemotherapy were enrolled. Patients were randomly assigned double-blind 1:1 to switch maintenance pembrolizumab 200 mg intravenously once every 3 weeks versus placebo for up to 24 months. Patients with disease progression on placebo could cross over to pembrolizumab. The primary objective was to determine the progression-free survival. Secondary objectives included determining overall survival as well as treatment outcomes according to PD-L1 combined positive score (CPS). RESULTS Between December 2015 and November 2018, 108 patients were randomly assigned to pembrolizumab (n = 55) or placebo (n = 53). The objective response rate was 23% with pembrolizumab and 10% with placebo. Treatment-emergent grade 3-4 adverse events occurred in 59% receiving pembrolizumab and 38% of patients receiving placebo. Progression-free survival was significantly longer with maintenance pembrolizumab versus placebo (5.4 months [95% CI, 3.1 to 7.3 months] v 3.0 months [95% CI; 2.7 to 5.5 months]; hazard ratio, 0.65; log-rank P = .04; maximum efficiency robust test P = .039). Median overall survival was 22 months (95% CI, 12.9 months to not reached) with pembrolizumab and 18.7 months (95% CI, 11.4 months to not reached) with placebo. There was no significant interaction between PD-L1 CPS ≥ 10 and treatment arm for progression-free survival or overall survival. CONCLUSION Switch maintenance pembrolizumab leads to additional objective responses in patients achieving at least stable disease with first-line platinum-based chemotherapy and prolongs progression-free survival in patients with metastatic urothelial cancer.

scholarly journals Double-Blind, Randomized Trial of Docetaxel Plus Vandetanib Versus Docetaxel Plus Placebo in Platinum-Pretreated Metastatic Urothelial Cancer

2012 ◽  
Vol 30 (5) ◽  
pp. 507-512 ◽  
Author(s):  
Toni K. Choueiri ◽  
Robert W. Ross ◽  
Susanna Jacobus ◽  
Ulka Vaishampayan ◽  
Evan Y. Yu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Urothelial Cancer ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Double Blind ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

Purpose Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy. Patients and Methods The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m2 intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided α at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives. Results In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months. Conclusion In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.

scholarly journals Pembrolizumab versus chemotherapy in recurrent, advanced urothelial cancer in Japanese patients: a subgroup analysis of the phase 3 KEYNOTE-045 trial

2019 ◽  
Vol 25 (1) ◽  
pp. 165-174 ◽  
Author(s):  
Hiroyuki Nishiyama ◽  
Yoshiaki Yamamoto ◽  
Naoto Sassa ◽  
Kazuo Nishimura ◽  
Kiyohide Fujimoto ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Open Label ◽  
End Points ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

Abstract Background The open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine). Pembrolizumab is approved for patients with bladder cancer in Japan. Patients and methods Analysis was performed in the subgroup of Japanese patients enrolled in the KEYNOTE-045 study. Coprimary end points were OS and progression-free survival (PFS). Objective response rate (ORR) and safety were secondary end points. Results Fifty-two Japanese patients (pembrolizumab, n = 30; chemotherapy, n = 22) were followed up for a median of 26.1 months. Patients who received pembrolizumab compared with chemotherapy had a 19% lower risk for death (hazard ratio [HR] 0.81, 95% CI 0.44–1.50); after adjusting for baseline covariates, the HR for OS was 0.61 (95% CI 0.32–1.15). The 24-month OS rate was higher with pembrolizumab (26.9% vs 14.3%). PFS was 2.0 and 4.9 months for pembrolizumab and chemotherapy, respectively (HR 1.71, 95% CI 0.95–3.08). ORR was similar for pembrolizumab and chemotherapy (20.0% vs 18.2%); durability of response was higher with pembrolizumab: 67% and 33% of patients, respectively, maintained a response for > 12 months. Treatment-related adverse events, including grade 3–5 events, occurred less frequently with pembrolizumab. Conclusions Pembrolizumab provided durable antitumor activity in patients with locally advanced/metastatic UC that progressed after platinum-containing chemotherapy in the overall population and in the Japanese subgroup; safety profile was consistent with that previously observed for pembrolizumab.

Phase Ib/II trial of lenvatinib plus pembrolizumab in urothelial cancer.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 11-11 ◽  
Author(s):  
Nicholas J. Vogelzang ◽  
Carlos A. Encarnacion ◽  
Allen Lee Cohn ◽  
Christopher DiSimone ◽  
Drew W. Rasco ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Advanced Urothelial Cancer ◽  
Line Setting

11 Background: Pembrolizumab (PEM), an anti-PD-1 antibody, is approved for advanced urothelial cancer in the second-line setting (objective response rate [ORR] 21%) and in the first-line setting for patients (pts) ineligible for cisplatin with combined positive score ≥10 or ineligible for platinum-based chemotherapy (ORR 29%). Tyrosine kinase inhibitors such as lenvatinib (LEN; a multikinase inhibitor of VEGFR 1-3, FGFR 1-3, PDGFRα, RET and KIT) have demonstrated activity in urothelial cancer and may reverse the immunosuppressive environment that leads to immuno-oncology (IO) failure. We present a phase 1b/2 trial of LEN + PEM in advanced urothelial cancer. Methods: In this multicenter, open-label study, pts with confirmed metastatic urothelial cancer and ECOG PS of 0 or 1 received oral LEN 20 mg/day + PEM (200 mg Q3W, IV). Pts were not preselected for PD-L1 status. The phase 2 primary end point was investigator-assessed ORR at week 24 (ORRwk24) per immune-related RECIST (irRECIST). Secondary end points included ORR, duration of response (DOR), and progression-free survival (PFS). Results: At data cutoff (March 1, 2018), 20 pts were enrolled: 9 (45%) PD-L1(+), 5 (25%) PD-L1(-); 6 (30%) not tested. 4 Pts (20%) were treatment-naïve; 11 (55%) and 5 (25%) pts had had 1 and 2 lines of prior anticancer therapies, respectively. No pt had received prior IO. ORRwk24 was 25% (95% CI: 8.7–49.1). 18 (90%) pts had ≥1 treatment-related adverse event (TRAE). Grade 3 and 4 TRAEs occurred in 5 (25%) and 5 (25%) pts, respectively. There was 1 fatal TRAE (gastrointestinal hemorrhage). The most common any-grade TRAEs were proteinuria (45%), diarrhea (40%), fatigue (30%), hypertension (30%), and hypothyroidism (30%). Conclusions: LEN + PEM demonstrated activity in this study of pts with advanced urothelial cancer, which included pts receiving later-line treatment, and deserves further investigation. Clinical trial information: NCT02501096. [Table: see text]

A double-blind randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated advanced urothelial cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. LBA239-LBA239 ◽  
Author(s):  
T. K. Choueiri ◽  
U. N. Vaishampayan ◽  
E. Y. Yu ◽  
D. I. Quinn ◽  
N. M. Hahn ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Double Blind ◽  
Molecule Inhibitor ◽  
Platinum Based Chemotherapy ◽  
Visceral Metastases ◽  
Advanced Urothelial Cancer ◽  
Ecog Ps

LBA239 Background: Vandetanib (V) is a novel small-molecule inhibitor that targets key signaling pathways in cancer including VEGF and EGF. V in combination with docetaxel (D) was assessed in patients (pts) who received prior platinum-based chemotherapy for advanced urothelial cancer (UC). Methods: Patients eligible for this randomized, multicenter, double-blind, investigator-initiated trial had metastatic UC after failure of prior platinum-based chemotherapy. Up to 3 prior therapies were allowed including paclitaxel. The primary objective was to determine whether once-daily oral V (100 mg) + D (75 mg/m2 IV q21 days) prolonged progression-free survival (PFS) vs. placebo (P) + D (80% power to detect 60% improvement in median PFS with 1-sided α=0.05). Patients on D+P, had the option to cross over to single agent V. Overall survival (OS), overall response rate (ORR), stable disease (SD), and safety were secondary objectives. Results: One-hundred and forty-two pts were enrolled at 16 institutions, 68% men; median age 65y; ECOG PS 0/1: 52%/48%; visceral involvement: 66%. 80% of patients had ECOG PS 1 and/or visceral metastases. 44% of patients had 2 or more prior systemic therapies and 15% had prior paclitaxel. Baseline characteristics were balanced in both arms. Median PFS was 11.1 weeks (wks) for D+V arm vs. 6.9 wks for D+P arm (HR=1.04, p=0.92). Median OS was 25.4 wks for the D+V arm vs. 30.6 wks for the D+P arm (HR 1.21, p=0.35). ORR was 7.1% for the D+V arm vs. 11.1% for the D+P arm (OR=0.6, 90% CI [0.2–1.6]). SD or better rates were 50.0% vs. 37.5% on D+V and D+P, respectively. As of December 2010, 5 pts were on therapy and 70% of pts died. Median follow-up for pts still alive is 7.2 months. Treatment-related grade >3 toxicities for D+V arm was 60% vs. 36% for the D+P arm (p=0.055) and were generally manageable (grade 4, 14% vs. 11%). Grade >3 toxicities that were more commonly seen in the D+V arm were rash/photosensitivity (11% vs. 0%) and diarrhea (7% vs. 0%). Conclusions: In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR or OS. Toxicities were greater but manageable. [Table: see text]

Final results of a randomized, double-blind, phase II study of gemcitabine plus vandetanib or plus placebo in the treatment of advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) elderly patients (ZELIG study NCT00753714).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7550-7550 ◽  
Author(s):  
Cesare Gridelli ◽  
Silvia Novello ◽  
Nicoletta Zilembo ◽  
Paolo Foa ◽  
Adolfo G. Favaretto ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Standard Of Care ◽  
Primary Objective ◽  
Stage Iiib ◽  
Double Blind ◽  
Platinum Based Chemotherapy

7550 Background: Vandetanib (V) is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. Single-agent gemcitabine (G) is a standard of care option for unselected patients (pts) unfit for doublet platinum based chemotherapy. This study assessed the progression-free survival (PFS) benefit of G+V compared to G plus placebo (P) in pts with advanced NSCLC aged ≥ 70 years. Methods: Eligible pts (stage IIIB/IV NSCLC; WHO PS 0-2; all histologies; chemonaïve, aged ≥70) were randomized 1:1 to receive G 1200 mg/m2 i.v. day 1 and 8 of each 21-day cycle, up to 6 cycles plus V 100 mg/day or plus P until progression/toxicity. The primary objective was PFS (80% power to detect a hazard ratio [HR] ≤ 0.667). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Between Oct 2008-May 2010, 124 pts (median age 75 yrs (70-84); 72.6% male; 57.2% WHO PS 0-1; 74.2% past/never-smoker; 58.1% adenocarcinoma; 89.5% stage IV) were randomized to G+V (n = 61) or G+P (n = 63). Baseline characteristics were similar in both arms. At data cut-off (Apr11), 87.9% pts progressed and 73.4% pts had died. PFS was significantly prolonged for G+V (HR=0.729; 95% CI 0.484-1.096; p=0.0417), median PFS G+V=6.0 months, G+P=5.5 months. No differences were seen in ORR (14.8% and 12.7%; p = 0.74), DCR (72.1% and 66.7%; p =0.51), OS (HR=1.024 [95% CI 0.667-1.571] p=0.8960), proportion of pts alive at 1-year G+V=31.1% and G+P=30.2% (p=0.90). Adverse events (AEs) observed for V 100 mg were generally consistent with previous NSCLC studies of V 100 mg. Common AEs (any grade) occurring with a greater frequency in the G+V arm included skin toxicity (34.4% vs 15.9%) and hypertension (9.8% vs 3.2%). Diarrhea and neutropenia were similar in both arms (14.8% and 14.3%; 19.7% and 19.0%). Conclusions: Despite a marginally statistically significant improvement in PFS the study did not met the primary and secondary end points. The combination G+V was well tolerated in this clinical setting.

scholarly journals Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma

2012 ◽  
Vol 30 (28) ◽  
pp. 3545-3551 ◽  
Author(s):  
Yu-Ning Wong ◽  
Samuel Litwin ◽  
David Vaughn ◽  
Seth Cohen ◽  
Elizabeth R. Plimack ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Metastatic Setting ◽  
Previously Treated ◽  
Grade 3

Purpose The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer. Patients and Methods Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m2 with or without paclitaxel 80 mg/m2 per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks. Results We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases). Conclusion Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.

scholarly journals The Efficacy of Ramucirumab in the Treatment of Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis of RCTs

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hongqiong Yang ◽  
Yaojun Zhou ◽  
Liangzhi Wang ◽  
Tianyi Gu ◽  
Mengjia Lv ◽  
...  
Keyword(s):  
Response Rate ◽  
Meta Analysis ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
First Line ◽  
Free Survival ◽  
Gastroesophageal Junction Cancer ◽  
Line Chemotherapy

Five electronic databases were searched for eligible records. Outcomes were presented and analyzed according to the objective response rate (ORR), progression-free survival (PFS) rate, and overall survival (OS) rate. Five records involving 2,024 participants were included in the study. The pooled analysis of OS and PFS were longer with ramucirumab (RAM) therapy than without RAM for OS (odds ratio OR = 0.90 , 95% confidence interval CI = 0.82 – 1.00 , p = 0.05 ) and PFS ( OR = 0.74 , 95 % CI = 0.57 – 0.96 , p = 0.02 ). Moreover, compared with the current first-line chemotherapy, the OS ( OR = 0.93 , 95 % CI = 0.83 – 1.04 , p = 0.19 ) and PFS ( OR = 0.82 , 95 % CI = 0.64 – 1.06 , p = 0.13 ) results were not significantly higher with RAM. The ORRs of the patients in the RAM therapy groups were significantly higher than those in the groups without RAM ( OR = 1.40 , 95 % CI = 1.14 – 1.73 , p = 0.001 ).

scholarly journals Atezolizumab in locally advanced or metastatic urothelial cancer: a pooled analysis from the Spanish patients of the IMvigor 210 cohort 2 and 211 studies

2020 ◽  
Author(s):  
M. Sotelo ◽  
T. Alonso-Gordoa ◽  
P. Gajate ◽  
E. Gallardo ◽  
R. Morales-Barrera ◽  
...  
Keyword(s):  
Median Duration ◽  
Urothelial Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Pooled Analysis ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Geographical Regions ◽  
Duration Of Response

Abstract Background The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown. Materials and methods We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells. Results Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months; p = 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm [46/57 (81%) vs 44/74 (59%)]. Conclusion Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab.

Vandetanib versus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one prior cytotoxic chemotherapy: A randomized, double-blind phase III trial (ZEST)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8009-8009
Author(s):  
R. B. Natale ◽  
S. Thongprasert ◽  
F. A. Greco ◽  
M. Thomas ◽  
C. M. Tsai ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind ◽  
Equivalent Efficacy ◽  
Secondary Endpoints ◽  
Previously Treated ◽  
Grade 3 ◽  
To Receive

8009 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. This phase III study compared the efficacy of vandetanib vs erlotinib in patients (pts) with advanced, previously treated NSCLC. Methods: Eligible pts (stage IIIB/IV NSCLC, PS 0–2, 1–2 prior chemotherapies; all histologies permitted) were randomized 1:1 to receive vandetanib 300 mg/day or erlotinib 150 mg/day until progression/toxicity. The primary objective was to show superiority in progression-free survival (PFS) for vandetanib vs erlotinib. Secondary endpoints included overall survival (OS), objective response rate (ORR), time to deterioration of symptoms (TDS; EORTC QoL Questionnaire) and safety. Results: Between Oct 06-Nov 07, 1240 pts (mean age 61 yrs; 38% female; 22% squamous) were randomized to receive vandetanib (n=623) or erlotinib (n=617). Baseline characteristics were similar in both arms. Median duration of follow-up was 14 months, with 88% pts progressed and 67% dead. There was no difference in PFS for pts treated with vandetanib vs erlotinib (hazard ratio [HR] 0.98, 95.22% CI 0.87–1.10; P=0.721), and no difference in the secondary endpoints of OS (HR 1.01, 95.08% CI 0.89–1.16; P=0.830), ORR (both 12%) and TDS (pain: HR 0.92, P=0.289; dyspnea: HR 1.07, P=0.407; cough: HR 0.94, P=0.455). A preplanned non-inferiority analysis for PFS and OS demonstrated equivalent efficacy for vandetanib and erlotinib. The adverse events (AEs) observed for vandetanib were generally consistent with previous NSCLC studies with vandetanib 300 mg. There was a higher incidence of some AEs (any grade) with vandetanib vs erlotinib, including diarrhea (50% vs 38%) and hypertension (16% vs 2%); rash was more frequent with erlotinib (38% vs 28%). The overall incidence of CTCAE grade ≥3 AEs was also higher with vandetanib (50% vs 40%). The incidence of protocol-defined QTc prolongation in the vandetanib arm was 5%. Conclusions: The study did not meet its primary objective of demonstrating PFS prolongation with vandetanib vs erlotinib in pts with previously treated advanced NSCLC. However, vandetanib and erlotinib showed equivalent efficacy for PFS and OS in a preplanned non-inferiority analysis. [Table: see text]

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