Phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC): Asian subgroup analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7549-7549
Author(s):  
Yukito Ichinose ◽  
Kaoru Kubota ◽  
Giorgio Scagliotti ◽  
David R. Spigel ◽  
Joo-Hang Kim ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Phase Iii ◽  
Stage Iv Disease ◽  
Phase Iii Study ◽  
Prior Systemic Therapy ◽  
Mortality Table ◽  
Nonsquamous Nsclc

7549 Background: MONET1 evaluated overall survival (OS) in patients (pts) with nonsquamous NSCLC receiving motesanib (an oral VEGFR 1, 2 and 3, PDGFR and Kit inhibitor) plus C/P compared with pts receiving placebo plus C/P. Analysis of the total population (N=1090) showed that motesanib + C/P did not significantly improve OS vs C/P alone (primary endpoint). Here we present results of a subgroup analysis of Asian pts. Methods: Asian pts (Japan, S. Korea, Philippines, Hong Kong, Taiwan, Singapore) with stage IIIB/IV or recurrent nonsquamous NSCLC and no prior systemic therapy for advanced NSCLC were analysed. Pts were randomized to up to six 3-wk cycles of C (AUC 6 mg/mL·min) and P (200 mg/m2) with either motesanib 125 mg QD (Arm A) or placebo QD (Arm B) orally continuously. Results: 227 Asian pts (incl. 106 Japanese pts) with nonsquamous NSCLC were randomized (Arm A/B, n=110/117); 198 had adenocarcinoma (n=97/101). Median age was 60 y (range 30–78); 80% had stage IV disease. At the time of analysis, 139 pts had died (118 pts with adenocarcinoma). Pts received a median of 164 days of motesanib vs 125 days of placebo (vs 106 and 126 days in non-Asian pts). Median follow-up was 63 wks. Efficacy results are shown in the table. Motesanib/placebo-related AEs were seen in 94/74% of pts respectively; Gr ≥3 related AEs in 48/22%. Most common emergent AEs were (Arm A/B) alopecia (78/76%), diarrhea (63/33%), and nausea (55/43%); gallbladder disorders (Gr 1–2) were seen in 9/2% of pts. Gr ≥3 AEs more frequent in Arm A vs B included neutropenia (36/22%) and hypertension (13/3%). Emergent Gr 5 events were seen in (Arm A/B) 5/4% vs 16/11% in non-Asian pts. Conclusions: In contrast to non-Asian pts, in the subgroup of Asian pts with advanced nonsquamous NSCLC, motesanib plus C/P treatment was associated with increased OS, PFS, and objective response rates (ORR) compared with C/P alone, with no excess of treatment-related mortality. [Table: see text]

High complete response (CR) rate in patients (pts) with esophageal carcinoma (EC) undergoing neoadjuvant combination of docetaxel and cisplatin (DC) ± cetuximab(DCE) chemoradiation therapy—a retrospective analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15093-15093
Author(s):  
T. J. Fillos ◽  
P. Hentschel ◽  
K. Watkins ◽  
M. S. Karpeh ◽  
A. Meek ◽  
...  
Keyword(s):  
Objective Response ◽  
Pathologic Complete Response ◽  
Stage Iv ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
High Rate ◽  
Phase Iii ◽  
Weekly Docetaxel ◽  
Stage Iv Disease ◽  
Grade 3

15093 Background: EC is a highly lethal disease with 5 year survival less than 15%. Surgery offers a chance for cure in early disease. Still, fewer than 20% of pts treated with surgery alone are alive at 5 years. Neoadjuvant chemoradiation offers the theoretical advantage of increasing R0 resections and reducing early local and distal metastases which may translate into improved survival. Several clinical trials have resulted in pathologic complete response (pCR) rates of 20–30%. Methods: Newly diagnosed pts with EC Stage 2A (T3) to 4 received weekly Docetaxel (D)25–30mg/m2 and Cisplatin (C)25–30mg/m2.for 6–8 weeks concurrently with radiation, 5040 cGy in 28 fractions. Cetuximab (E) 200mg/m2 was added after it became accepted treatment in head and neck cancers. Pts were scheduled 4 - 6 weeks later for surgery followed by the same chemotherapy for total of 16 weeks of treatment. Pts were assessed for time to progression, overall survival and toxicities. Results: Fifteen pts treated in 2005–6 underwent IRB approved evaluation; 11 male and 4 female, median age of 62(range 44–78) . Four had squamous cell (SCC) and 11 adenocarcinomas. Nine pts had Stage II, 4 pts stage III and 2 pts stage IV disease. Seven pts underwent surgery, all R0 resections. Four of them had pCR, one pPR (downstaged from T3 to T1) and two pts had stable disease. An additional 3 pts had radiological and endoscopic proven CR (medically not surgical candidates) for an objective response (CR+PR) in 8 out of 15 pts (3 SCC and 5 adenoca). Five out of 9 receiving DC had an objective response while 3 of 6 receiving DCE responded. Five pts progressed prior to surgery. Grade 3/4 neutropenia occurred in 2, nausea in 3, and 1 pt experienced Grade 3 dehydration. Four patients required dose reductions by 20%. Six patients had one cycle and 2 had 3 cycles delayed by one week each. Conclusions: Neoadjuvant chemoradiation treatment with weekly Docetaxel and Cisplatin ± Cetuximab is tolerable with high rate of CRs. There was no observed difference in response with the addition of cetuximab. A Phase III study is suggested. No significant financial relationships to disclose.

An international, randomized, placebo-controlled, double-blind phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC).

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA7512-LBA7512 ◽  
Author(s):  
G. Scagliotti ◽  
I. Vynnychenko ◽  
Y. Ichinose ◽  
K. Park ◽  
K. Kubota ◽  
...  
Keyword(s):  
Cox Model ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Rate ◽  
Phase Iii ◽  
Rank Test ◽  
Double Blind ◽  
Grade 3 ◽  
Nonsquamous Nsclc

LBA7512 Background: This study evaluated whether motesanib (a selective oral inhibitor of VEGFR 1, 2 and 3; PDGFR and Kit) plus C/P improved overall survival (OS) compared with placebo + C/P in patients (pts) with nonsquamous NSCLC and in a subset of pts with adenocarcinoma. Methods: Pts had stage IIIB/IV or recurrent nonsquamous NSCLC and no prior systemic therapy for advanced NSCLC. The study initially enrolled all histologies but was amended to exclude pts with squamous NSCLC owing to a high rate of hemoptysis. Pts were randomized 1:1 to receive up to six 3-wk cycles of C (AUC 6 mg/mL·min) and P (200 mg/m2) with either motesanib 125 mg QD (Arm A) or placebo QD (Arm B) orally continuously. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), adverse events (AEs), objective response rate (ORR) and association between placental growth factor (PLGF) change and OS. OS was evaluated using a stratified Cox model and 2-sided log-rank test (α=0.03 for nonsquamous pts and α=0.02 for adenocarcinoma pts). Results: 1090 pts with nonsquamous NSCLC were randomized (Arm A/B, n=541/549); 890 had adenocarcinoma (n=448/442). 61% were men; median age was 60 years (range 21–87); 83% had stage IV disease. At the time of analysis, 753 pts had died (608 pts with adenocarcinoma). Median follow-up was 10.6 mo. OS was not significantly improved in Arm A compared with Arm B (Table). In Arm A, PLGF analysis did not show an association with OS. The incidence of grade ≥3 AEs in Arms A/B was 73/59%. Grade ≥3 AEs occurring more frequently in Arm A than B included neutropenia (22/15%), diarrhea (9/1%), hypertension (7/1%) and cholecystitis (3/0%). The incidence of grade 5 AEs was 14/9% in Arms A/B. Conclusions: In pts with advanced nonsquamous NSCLC, treatment with motesanib + C/P did not significantly improve OS compared with C/P alone. [Table: see text]

A single-arm, open-label, U.S. expanded access study of vemurafenib in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8567-8567
Author(s):  
Lynn Mara Schuchter ◽  
Lawrence E. Flaherty ◽  
Omid Hamid ◽  
Gerald P. Linette ◽  
Sigrun Hallmeyer ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Response Rate ◽  
Phase Iii ◽  
Open Label ◽  
Expanded Access ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
Prior Systemic Therapy ◽  
Ecog Ps

8567 Background: Vemurafenib (vem) has been FDA approved for the treatment of unresectable or metastatic BRAFV600E mutated melanoma since August 2011 based on results of a randomized phase III study (treatment-naive) and a single arm phase II study (previously treated). We report results of an expanded access study that allowed appropriate patients (pts) to receive vem until the drug was approved. Methods: Eligible pts had metastatic melanoma with a BRAFV600E mutation as detected by the cobas 4800 BRAFV600 Mutation Test. Enrolled pts received oral vem 960 mg b.i.d. Adverse events (AEs) were evaluated for vem-related toxicities; tumor responses were assessed using RECIST 1.1. Results: 29 US sites screened 745 pts and enrolled 374 from December 2010 until October 2011. The following results are based on a median follow up time and treatment duration of 2 months. At baseline, mean age of pts was 54 y with 22% of pts ≥65 y; 75% had stage M1c disease; 29% had received radiotherapy for brain metastases. 19% of pts were ECOG PS 2 or 3; 71% of pts had prior systemic therapy for metastatic melanoma (21% 1 regimen; 50% ≥2 regimens). 50 pts had prior adjuvant treatment. At data cut-off, 243 pts had sufficient follow-up time for tumor assessment. In this group, the unconfirmed overall response rate was 52% (95% CI, 46 to 59). The median time to response was 1.8 months. Based on 240 pts with available ECOG PS status at time of analysis, response rate was 53% for pts with ECOG PS 0 or 1 (n=209), and 45% for pts with ECOG PS 2 or 3 (n=31). 370 pts were evaluable for safety analysis. The most common vem-related AEs were rash (36%), arthralgia (33%) and fatigue (21%) with the majority (~90%) of grade 1 or 2. 25 vem-related serious AEs were reported in 5.4% of pts with a slightly higher rate of pts with ECOG PS 2 or 3 (8.7%) compared to ECOG PS 0 or 1 (4.7%). 18% of pts missed at least one dose and 11% of pts required dose reduction of at least one level due to AEs. Conclusions: This expanded access study, with its limited follow-up time, confirms the established rapid and high tumor response rate with vem. No new safety signals were detected. Compared to the overall population, pts with an ECOG PS 2 or 3 demonstrated a similar benefit.

Efficacy of pemetrexed-cisplatin (PC) in East Asian patients (pts): Subgroup analysis of a phase III study comparing PC versus gemcitabine-cisplatin (GC) in first-line treatment of advanced non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8045-8045
Author(s):  
M. Orlando ◽  
J. S. Lee ◽  
C. Yang ◽  
L. Simms ◽  
K. Park
Keyword(s):  
Subgroup Analysis ◽  
Smoking Status ◽  
East Asian ◽  
Phase Iii ◽  
Smoking History ◽  
Asian Ethnicity ◽  
Disease Characteristics ◽  
Phase Iii Study ◽  
Egfr Tkis ◽  
Nonsquamous Nsclc

8045 Background: East Asian ethnicity is a recognized favorable prognostic factor in the treatment of NSCLC in trials with either chemotherapy or EGFR tyrosine-kinase inhibitors (TKIs). In a global phase III study (Scagliotti JCO 2008), superior efficacy of PC was shown for pts with nonsquamous NSCLC, while Asian ethnicity was prognostic in the overall population. The purpose of this analysis is to describe the patient and disease characteristics of the East Asian pts enrolled in this study and assess efficacy according to histology and smoking history. Methods: This retrospective analysis of a large phase III study included only patients enrolled from Korea and Taiwan. For survival and progression-free survival (PFS), Cox-adjusted analyses were used to estimate the hazard ratio and 95% CI, while medians were estimated using Kaplan-Meier method. Results: Results for PFS and response rate showed trends similar to overall survival in East Asian pts, favoring PC therapy in nonsquamous pts. The use of post-discontinuation targeted therapies such as EGFR-TKIs was similar between treatment arms in the overall population and in nonsquamous pts. In East Asian pts, EGFR-TKI use was slightly higher in the GC arm, in both the overall population and in nonsquamous pts. In a further subgroup analysis defined by smoking status, East Asian nonsquamous pts treated with PC had longer survival (not statistically significant). Conclusions: Pt and disease characteristics between the East Asian subgroup and the overall population were similar, with notable differences in the percentage of pts with no smoking history and the greater use of EGFR-TKIs as post-discontinuation therapy. This analysis shows the improved efficacy outcomes for East Asian nonsquamous pts treated with PC is consistent with the previously observed treatment effect of PC on nonsquamous NSCLC. [Table: see text] [Table: see text]

IMbrave150: Updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 267-267
Author(s):  
Richard S. Finn ◽  
Shukui Qin ◽  
Masafumi Ikeda ◽  
Peter R. Galle ◽  
Michel Ducreux ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Open Label ◽  
Treatment Benefit ◽  
Recist 1.1 ◽  
Open Label Phase ◽  
Phase Iii Study

267 Background: Atezo + bev has been approved globally for pts with unresectable HCC who have not received prior systemic therapy, based on results from IMbrave150 (NCT03434379). At a median of 8.6 mo follow-up, both coprimary endpoints were met, with statistically significant and clinically meaningful improvements observed with atezo + bev vs sor for OS (HR, 0.58 [95% CI, 0.42, 0.79]; P<0.001) and independently-assessed progression-free survival (PFS; per RECIST 1.1; HR, 0.59 [95% CI, 0.47, 0.76]; P<0.001) (Finn, et al. N Engl J Med 2020). Here, we report an updated OS analysis for IMbrave150. Methods: The global, multicenter, randomized, open-label, Phase III study IMbrave150 enrolled 501 systemic treatment–naive pts with unresectable HCC, ≥1 measurable untreated lesion (RECIST 1.1), Child-Pugh class A liver function and ECOG PS 0/1. Pts were randomized 2:1 to receive either atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical benefit per investigator. This post hoc, descriptive OS analysis was conducted with 12 mo of additional follow up from the primary analysis. Results: 501 pts were enrolled, including 336 to atezo + bev and 165 to sor. At the clinical cut-off date of Aug 31, 2020, median follow-up was 15.6 mo and 280 OS events were observed. Median OS was 19.2 mo with atezo + bev vs 13.4 mo with sor (HR, 0.66 [95% CI, 0.52, 0.85]; P=0.0009). Survival at 18 mo was 52% with atezo + bev and 40% with sor. Survival benefit with atezo + bev over sor was generally consistent across subgroups and with the primary analysis. The updated objective response rate (ORR; 29.8% per RECIST 1.1) with atezo + bev was in line with the primary analysis, with more pts achieving complete response (CR; 7.7%) than previously reported. Additional response data are in Table. Safety was aligned with the primary analysis, with no new signals identified. Conclusions: IMbrave150 showed consistent clinically meaningful treatment benefit and safety with 12 mo of additional follow-up. The combination provides the longest survival seen in a front-line Phase III study in advanced HCC, confirming atezo + bev as a standard of care for previously untreated, unresectable HCC. Clinical trial information: NCT03434379. [Table: see text]

scholarly journals Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma

2021 ◽  
Author(s):  
Jedd D. Wolchok ◽  
Vanna Chiarion-Sileni ◽  
Rene Gonzalez ◽  
Jean-Jacques Grob ◽  
Piotr Rutkowski ◽  
...  
Keyword(s):  
Descriptive Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Phase Iii ◽  
End Points ◽  
Unresectable Stage

PURPOSE In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes. PATIENTS AND METHODS Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary end points were progression-free survival and overall survival (OS) with nivolumab plus ipilimumab or nivolumab versus ipilimumab. Secondary end points included objective response rate, descriptive efficacy assessments of nivolumab plus ipilimumab versus nivolumab alone, and safety. Melanoma-specific survival (MSS; descriptive analysis), which excludes deaths unrelated to melanoma, was also evaluated. RESULTS Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively. Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with BRAF-mutant tumors and 46%, 42%, and 22% in those with BRAF–wild-type tumors, respectively. In patients who discontinued treatment, the median treatment-free interval was 27.6, 2.3, and 1.9 months, respectively. Since the 5-year analysis, no new safety signals were observed. CONCLUSION These 6.5-year CheckMate 067 results, which include the longest median OS in a phase III melanoma trial reported to date and the first report of MSS, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy.

IMpower131: Primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC.

2018 ◽  
Vol 36 (18_suppl) ◽  
pp. LBA9000-LBA9000 ◽  
Author(s):  
Robert M. Jotte ◽  
Federico Cappuzzo ◽  
Ihor Vynnychenko ◽  
Daniil Stroyakovskiy ◽  
Delvys Rodriguez Abreu ◽  
...  
Keyword(s):  
Stage Iv ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Individual Treatment ◽  
Primary Analysis ◽  
Phase Iii Study ◽  
Grade 3 ◽  
The Individual ◽  
Clinical Trial Information

LBA9000 Background: Atezolizumab (atezo; anti–PD-L1) demonstrated OS benefit vs docetaxel in 2L+ NSCLC regardless of PD-L1 status or tumor histology. Because cytotoxic agents can exhibit positive immunomodulatory effects, combining atezo with chemotherapy may further improve outcomes. IMpower131 (NCT02367794) was designed to evaluate atezo + carboplatin (carbo) + paclitaxel (pac) or nab-paclitaxel (nab-pac) in 1L stage IV squamous NSCLC. Methods: Patients (pts) were randomized 1:1:1 to Arm A (atezo 1200 mg q3w + carbo AUC 6 q3w + pac 200 mg/m2 q3w), Arm B (atezo + carbo + nab-pac 100 mg/m2 weekly) or Arm C (carbo + nab-pac). Pts received chemotherapy for 4 or 6 cycles and atezo until loss of clinical benefit. We present the primary analysis of investigator (INV)-assessed PFS per RECIST v1.1 in the ITT population for Arm B vs Arm C. Data cutoff: 22 January 2018. Results: 338 pts (Arm A), 343 pts (Arm B) and 340 pts (Arm C) were enrolled. Minimum follow-up was 9.8 mo. INV-assessed median PFS was 6.3 mo in Arm B vs 5.6 mo in Arm C (HR, 0.715; 95% CI: 0.603, 0.848; P = 0.0001). PFS benefit was enriched in all PD-L1–positive IHC subgroups and was most pronounced in TC3 or IC3. AEs related to any treatment (TRAEs) were 91.3% (Arm A), 94.6% (Arm B) and 90.7% (Arm C); Grade 3-4 TRAEs were 42.8% (Arm A), 68.0% (Arm B) and 56.9% (Arm C); serious TRAEs were 22.3% (Arm A), 20.4% (Arm B) and 10.5% (Arm C). Preliminary OS data will be presented. Conclusions: IMpower131 met its co-primary endpoint of INV-assessed PFS in the ITT population in Arm B vs Arm C. The safety profile of atezo + carbo + nab-pac or pac was consistent with the known risks of the individual treatment components; no new safety signals were identified. Clinical trial information: NCT02367794. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document