Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC).

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA109-LBA109 ◽  
Author(s):  
Luis Paz-Ares ◽  
Leora Horn ◽  
Hossein Borghaei ◽  
David R. Spigel ◽  
Martin Steins ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Minimal Improvement ◽  
Phase Iii Trials ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Nsclc Patients

LBA109 Background: Options for advanced non-SQ NSCLC patients (pts) who progress after platinum-based doublet chemotherapy (PT-DC) are limited, with minimal improvement in overall survival (OS). We report results from a randomized, global phase III study of NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC and tyrosine kinase inhibitor, if eligible. Methods: Pts were randomized to NIVO 3 mg/kg Q2W (n=292) or DOC 75 mg/m2 Q3W (n=290) until progression or discontinuation due to toxicity/other reasons. Primary objective was OS; Secondary objectives were investigator-assessed objective response rate (ORR; per RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression, quality of life, and safety. Results: NIVO demonstrated superior OS (HR=0.73; 96% CI: 0.59, 0.89; P=0.00155) and improved ORR (19.2% vs 12.4%; P=0.0235). HR for PFS was 0.92 (95% CI: 0.77, 1.11; P=0.393). PD-L1 expression was associated with benefit from NIVO (Table). In PD-L1+ pts, NIVO showed improved efficacy across all endpoints at predefined 1%, 5%, and 10% cut- points. Grade 3–5 drug-related AEs occurred in 10.5% (30/287) of NIVO and 53.7% (144/268) of DOC pts. No deaths were related to NIVO vs 1 DOC-related death. After discontinuation, 42.1% of NIVO and 49.7% of DOC pts received subsequent systemic therapy. Conclusions: NIVO demonstrated superior OS vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC. The safety profile of NIVO 3 mg/kg Q2W was favorable vs DOC. NIVO demonstrated survival benefit across histologies in two randomized phase III trials. Clinical trial information: NCT01673867. [Table: see text]

SAVOIR: A phase III study of savolitinib versus sunitinib in pts with MET-driven papillary renal cell carcinoma (PRCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5002-5002
Author(s):  
Toni K. Choueiri ◽  
Daniel Yick Chin Heng ◽  
Jae-Lyun Lee ◽  
Mathilde Cancel ◽  
Remy B Verheijen ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Chromosome 7 ◽  
Phase Iii ◽  
Open Label ◽  
Grade 3 ◽  
Dose Modifications

5002 Background: PRCC is the most common type of non-clear cell RCC, accounting for 10–15% of renal malignancies. As a subset of PRCC cases are MET-driven, MET inhibition may be an appropriate targeted treatment approach. In a single-arm Phase II study, savolitinib (AZD6094, HMPL‐504, volitinib), a highly selective MET-tyrosine kinase inhibitor, demonstrated antitumor activity in pts with MET-driven PRCC (Choueiri et al. JCO 2017). The Phase III SAVOIR study (NCT03091192) further assessed savolitinib vs standard of care sunitinib in pts with MET-driven PRCC. Methods: In this open-label (sponsor blinded), randomized study, pts with centrally confirmed MET-driven ( MET and/or HGF amplification, chromosome 7 gain and/or MET kinase domain mutations), metastatic PRCC were randomized to savolitinib 600 mg once daily (QD), or sunitinib 50 mg QD 4 weeks on / 2 weeks off. Primary objective was progression-free survival (PFS; RECIST 1.1 by blinded independent central review). Secondary objectives included overall survival (OS), objective response rate (ORR), and safety and tolerability. Results: After external data on predicted PFS with sunitinib in pts with MET-driven disease became available, study enrollment was closed. At data cutoff (Aug 2019), only 60 of the planned 180 pts were randomized (savolitinib n = 33; sunitinib n = 27). Most had chromosome 7 gain (savolitinib 91%; sunitinib 96%) and no prior therapy (savolitinib 85%; sunitinib 93%). PFS, OS, and ORR were numerically improved with savolitinib vs sunitinib (Table). CTCAE grade ≥3 adverse events (AEs) were reported in 42% and 81% of pts; dose modifications were related to AEs in 30% and 74% of pts with savolitinib and sunitinib respectively. After discontinuation, 36% of all savolitinib and 19% of all sunitinib pts received subsequent anticancer therapy. Conclusions: Although pt numbers and follow-up were limited, savolitinib demonstrated encouraging efficacy and an improved safety profile vs sunitinib, with fewer grade ≥3 AEs and fewer dose modifications required. Sunitinib performance was poorer than expected based on external retrospective data. Further investigation of savolitinib as a treatment option for MET-driven PRCC is warranted. Clinical trial information: NCT03091192 . [Table: see text]

An international, double-blind, randomized, placebo-controlled phase III trial (EXAM) of cabozantinib (XL184) in medullary thyroid carcinoma (MTC) patients (pts) with documented RECIST progression at baseline.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5508-5508 ◽  
Author(s):  
Patrick Schoffski ◽  
Rossella Elisei ◽  
Stefan Müller ◽  
Marcia S. Brose ◽  
Manisha H. Shah ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind ◽  
Efficacy Measure ◽  
Independent Review ◽  
Phase Iii Study ◽  
Grade 3

5508 Background: MTC arises from parafollicular cells of the thyroid gland, accounts for 5-8% of thyroid cancers and represents an unmet medical need. Cabozantinib (cabo) is an oral inhibitor of MET, VEGFR2, and RET. We conducted a phase III study of cabo vs placebo (P) in pts with progressive, unresectable, locally advanced or metastatic MTC. Methods: Eligible pts were required to have documented RECIST progression within 14 months of screening. The primary efficacy measure was progression-free survival (PFS) as assessed by an independent review facility (IRF) using RECIST. Secondary efficacy measures included objective response rate (ORR) and overall survival (OS). The study has 90% power to detect a 75% increase in PFS and 80% power to detect a 50% increase in OS. Tumor assessments occurred every 12 weeks. Crossover between treatment arms was not allowed. Results: Between Sept 2008 and Feb 2011, 330 pts (median age 55 yrs; 67% male; 96% measureable disease; RET mutation status: pos 48%; neg 12%; unknown 39%; prior TKI exposure: yes 21%, no 78%, unknown 2%) were randomized 2:1 to cabo (140 mg free base [175 mg salt form] qd; n=219) or P (n=111). The planned primary PFS analysis included events through the date of the 138th event. As of 15June2011, 44.7% of pts on cabo and 13.5% on P were still receiving study treatment. Statistically significant PFS prolongation of 7.2 mo was observed; median PFS for cabo was 11.2 mo vs 4.0 mo for P (HR 0.28, 95% CI 0.19-0.40, p<0.0001). PFS results favored the cabo group across subset analyses including RET status and prior TKI use. ORR was 28% for cabo vs 0% for P (p<0.0001). An interim analysis of OS (44% of the 217 required events) did not show a difference between cabo and P. The most frequent grade ≥3 adverse events (cabo vs P) were diarrhea (15.9 vs 1.8%), palmar-plantar erythrodysesthesia (12.6 vs 0%), fatigue (9.3 vs 2.8%), hypocalcemia (9.3 vs 0%), and hypertension (7.9 vs 0%). Conclusions: This phase III study met its primary objective of demonstrating substantial PFS prolongation with cabo vs. P in a patient population with MTC and documented progressive disease in need of therapeutic intervention.

Anlotinib combined with pemetrexed and carboplatin as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): ALTER L012.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Naïve ◽  
Nsclc Patients ◽  
First Line Treatment

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.

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]

Randomized phase III study of panitumumab (pmab) vs. cetuximab (cmab) in chemorefractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC): Outcomes by hypomagnesemia (hypomag) in ASPECCT.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 705-705
Author(s):  
Timothy Jay Price ◽  
Marc Peeters ◽  
Tae Won Kim ◽  
Jin Li ◽  
Stefano Cascinu ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Exon 2 ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Dose Modifications ◽  
Kras Exon

705 Background: ASPECCT met its primary endpoint of non-inferiority of overall survival (OS) of pmab vs. cmab. We evaluate outcomes by hypomag, an on-treatment, anti-EGFR related adverse event that develops due to the inhibition of EGFR function. Conflicting reports have suggested hypomag is associated with survival. Methods: Patients with previously treated WT KRAS exon 2 mCRC were randomized 1:1 to receive pmab or cmab. The primary endpoint was non-inferiority of OS. Progression-free survival (PFS) and objective response rate (ORR) were secondary endpoints. Patients were categorized ± any grade hypomag during the study and data analyzed by treatment arm. Analysis of Mg supplementation during hypomag was not conducted. Results: 999 patients were randomized and treated: 499 pmab, 500 cmab. Any grade hypomag was 28.8% and grade ≥3 was 7.3% in the pmab arm vs. 18.9% and 2.6% in the cmab arm, respectively. Median time to first hypomag onset was 82 days in the pmab arm and 57 days in the cmab arm. In the pmab arm, 1.0% of patients discontinued treatment and 5% of patients had dose modifications due to hypomag vs. <0.5% and 3% in the cmab arm, respectively. Results are shown (Table). Conclusions: In ASPECCT, rates of hypomag were higher in the pmab vs. the cmab arm. Patients who developed any grade hypomag with pmab or cmab had higher ORR, PFS, and OS compared with those patients who did not. Clinical trial information: NCT00788957. [Table: see text]

Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis.

2020 ◽  
Vol 38 (18_suppl) ◽  
pp. LBA1-LBA1 ◽  
Author(s):  
Thomas Powles ◽  
Se Hoon Park ◽  
Eric Voog ◽  
Claudia Caserta ◽  
B.P. Valderrama ◽  
...  
Keyword(s):  
Supportive Care ◽  
Stable Disease ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Primary Objective ◽  
Phase Iii ◽  
Platinum Based Chemotherapy ◽  
Grade 3

LBA1 Background: Platinum-based chemotherapy is an active 1L regimen for advanced UC; however, progression-free survival (PFS) and overall survival (OS) are generally short because of chemotherapy resistance. This randomized, phase 3 trial (JAVELIN Bladder 100; NCT02603432) evaluated avelumab (anti–PD-L1) as maintenance therapy following response or stable disease with 1L platinum-based chemotherapy in patients with advanced UC. Methods: Eligible patients with unresectable locally advanced or metastatic UC without disease progression after 4-6 cycles of gemcitabine with either cisplatin or carboplatin were randomized 1:1 to receive maintenance avelumab (10 mg/kg IV every 2 weeks) + best supportive care (BSC) or BSC alone, stratified by best response to 1L chemotherapy (complete/partial response vs stable disease) and by visceral vs nonvisceral disease when initiating 1L chemotherapy. The primary endpoint was OS, assessed from randomization in 2 primary populations: all randomized patients and patients with PD-L1+ tumors (Ventana SP263 assay). Secondary endpoints included PFS, objective response, and safety. Results: 700 patients were randomly assigned to maintenance avelumab + BSC (n=350) or BSC alone (n=350) and were followed for a median of 19.6 and 19.2 months, respectively. Overall, 358 (51%) had PD-L1+ tumors. Avelumab + BSC significantly prolonged OS vs BSC alone in all randomized patients (hazard ratio [HR] 0.69; 95% CI 0.56, 0.86; 1-sided p=0.0005); median OS with avelumab + BSC vs BSC alone was 21.4 vs 14.3 months, respectively. Avelumab + BSC also significantly prolonged OS vs BSC alone in patients with PD-L1+ tumors (HR 0.56; 95% CI 0.40, 0.79; 1-sided p=0.0003); median OS was not reached vs 17.1 months, respectively. An OS benefit was also observed across all prespecified subgroups. The HR for PFS based on blinded independent central review with avelumab + BSC vs BSC alone was 0.62 (95% CI 0.52, 0.75) in all randomized patients and 0.56 (95% CI 0.43, 0.73) in patients with PD-L1+ tumors. In treated patients in the avelumab + BSC (n=344) vs BSC alone (n=345) arms, respectively, all-causality adverse events (AEs) were reported at any grade in 98.0% vs 77.7% and at grade ≥3 in 47.4% vs 25.2%, and the most frequent grade ≥3 AEs were urinary tract infection (4.4% vs 2.6%), anemia (3.8% vs 2.9%), hematuria (1.7% vs 1.4%), fatigue (1.7% vs 0.6%), and back pain (1.2% vs 2.3%). Conclusions: JAVELIN Bladder 100 met its primary objective, demonstrating significantly prolonged OS with 1L maintenance avelumab + BSC vs BSC alone in advanced UC in all randomized patients and patients with PD-L1+ tumors. Efficacy benefits were seen across all prespecified subgroups, and the safety profile of avelumab was consistent with previous studies of monotherapy. Clinical trial information: NCT02603432 .

The NIBIT-M1 trial: Activity of ipilimumab plus fotemustine in patients with melanoma and brain metastases.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8529-8529 ◽  
Author(s):  
Michele Maio ◽  
Alessandro Testori ◽  
Paolo Antonio Ascierto ◽  
Ruggero Ridolfi ◽  
Mario Santinami ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Objective Response ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Free Survival ◽  
Brain Radiotherapy ◽  
Grade 3

8529 Background: Patients (pts) with metastatic melanoma (MM) often develop treatment-resistant brain metastases (mets). Treatment includes fotemustine (FTM), which crosses the blood-brain barrier. Ipilimumab (ipi) has shown activity in pts with MM and asymptomatic brain mets (Heller et al. ASCO 2011; abs 8581). In the phase II NIBIT-M1 trial, MM pts with asymptomatic brain mets were eligible for treatment with ipi plus FTM. Here, data from this pt subset are reported. Methods: Eligible pts received induction therapy with ipi 10 mg/kg every 3 wks (Q3W) x4 and FTM 100 mg/m2 weekly for 3 wks, followed by ipi Q12W from Week (W) 24 and FTM Q3W from W9. The primary objective was the immune-related (ir) disease control rate (irDCR: complete/partial response [CR/PR] or stable disease [SD] using the ir response criteria). Secondary objectives included ir objective response rate (ORR) and progression-free survival (PFS); overall survival (OS), and safety. Tumor assessments were performed Q8W from W12 to W36 and Q12W thereafter. Results: Among 86 enrolled pts, 20 had brain mets. Of these, 7 had prior whole brain radiotherapy (n=4) or radiosurgery (n=3). As of December 2011, the irDCR was 50% (10/20; 95% CI, 27.2–72.8%) with an irORR of 40% (95% CI, 19.1–63.9%: 2 CRs and 6 PRs). Pts with irDC also had stability/reduction (n=5) or disappearance (n=5) of brain mets. Among pts with progressive disease, all but one had progression in the brain. With median follow-up of 8.3 months (range: 0.4–16.9), median irPFS was 4.6 months (95% CI, 0.7–12.3). The 1-year OS rate was 52.9% (95% CI, 26.6–79.2); median OS was not reached. Induction with ipi and FTM was completed by 55% and 85% pts, respectively. Grade 3/4 drug-related adverse events (AEs) occurred in 60% pts; most commonly myelotoxicity (50%), increased ALT/AST (5%) and gastrointestinal (5%). AEs were generally manageable and reversible per protocol guidance. CNS AEs of any grade (i.e., haemorrhage, headache and seizure) occurred in 25% pts (grade 3/4 in 2 pts) and were attributed to disease progression. Conclusions: The combination of ipi plus FTM is active and safe in pts with MM and brain mets, regardless of prior treatment, and will be further explored in the phase III NIBIT-M2 trial.

Randomized phase II study of first-line everolimus plus bevacizumab (E+B) versus interferon α-2a plus bevacizumab (I+B) in patients (pts) with metastatic renal cell carcinoma (mRCC): Record-2 final overall survival (OS) and safety results.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4576-4576 ◽  
Author(s):  
Alain Ravaud ◽  
Carlos H. Barrios ◽  
Boris Y. Alekseev ◽  
Miah Hiang Tay ◽  
Sanjiv S. Agarwala ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Interferon Α ◽  
First Line ◽  
Primary Analysis ◽  
Safety Issues ◽  
Phase Iii Study ◽  
Subsequent Phase ◽  
Grade 3

4576 Background: RECORD-2 (NCT00719264) primary analysis demonstrated similar median progression-free survival (PFS) for pts with mRCC treated with E+B and I+B (Dec 2011 cut-off). The primary objective was not met; median PFS in E+B/I+B was 9.3/10.0 mo (HRIFN/EVE, 0.91; 95% CI, 0.69-1.19; P=0.485) and probability of success (PoS) of a subsequent phase III trial was 5.1%. Here we present final OS and safety/exposure results (Aug 2012 cut-off). Methods: Untreated pts with clear cell mRCC and previous nephrectomy were randomized 1:1 to B 10 mg/kg every 2 weeks and either E 10 mg/day or I (9 MIU 3 times/week). The primary objective was treatment effect on PFS per central review based on an estimation of PoS (≥50%) of a subsequent phase III study. Secondary objectives included OS and safety. Results: In E+B (n=182) and I+B (n=183) arms, median age was 60/60 years and 76/72% of pts were men, respectively. In both arms, most pts (93%) were of favorable/intermediate MSKCC risk. Median follow-up was 33 mo. In E+B and I+B arms, 51/52% of pts died, respectively. Median OS (95% CI) was 27.1 mo (19.9-35.3) in the E+B arm and 27.1 mo (20.4-30.8) in the I+B arm. After discontinuing study treatment, 64/60% of pts in E+B and I+B arms, respectively, received antineoplastic therapy. Median exposure duration in E+B and I+B arms was 8.5/8.3 mo, respectively; AEs resulted in treatment discontinuation for 23/25% of pts, respectively. The most frequent AEs (%) were stomatitis (63), proteinuria (50), diarrhea (40), hypertension (38), and epistaxis (35) in the E+B arm and decreased appetite (45), fatigue (42), proteinuria (38), asthenia (35), and pyrexia (35) in the I+B arm. The most frequent grade 3/4 AEs (%) were proteinuria (24), stomatitis (11), and anemia (11) for E+B and fatigue (17), asthenia (14), and proteinuria (10) for I+B. Conclusions: OS of E+B and I+B was similar. OS results are consistent with PFS primary analysis. First-line treatment with mTOR inhibitor-based therapy did not impair chance of survival relative to standard therapy. No new safety issues were identified and E+B remained generally well tolerated. Clinical trial information: NCT00719264.

A multicenter, randomized, blinded, phase III study of pasireotide LAR versus octreotide LAR in patients with metastatic neuroendocrine tumors (NET) with disease-related symptoms inadequately controlled by somatostatin analogs.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4031-4031 ◽  
Author(s):  
Edward M. Wolin ◽  
Barbara Jarzab ◽  
Barbro Eriksson ◽  
Thomas Walter ◽  
Christos Toumpanakis ◽  
...  
Keyword(s):  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Octreotide Lar ◽  
Predominant Symptom ◽  
Common Grade ◽  
Symptom Response ◽  
Phase Iii Study ◽  
Grade 3

4031 Background: The novel somatostatin analog (SSA) pasireotide has a broader binding profile than currently available SSA (octreotide and lanreotide). Results from a phase III study (NCT00690430) of pasireotide LAR (P) vs octreotide LAR (O) in patients (pts) with NET and disease-related symptoms uncontrolled by the maximum approved dose of available SSA are shown. Methods: Pts (N=110) were randomized and stratified by predominant symptom at baseline (diarrhea [D], flushing [F], or D+F) 1:1 to P (60 mg IM) or O (40 mg IM) q28d. Primary objective was symptom response at month (M) 6. Secondary objectives included tumor response and safety. Progression-free survival (PFS) was an exploratory analysis. Results: 53 and 57 pts were enrolled in the P and O arms when the study was halted due to an interim analysis suggesting futility for symptom response. Baseline characteristics were similar between arms. Majority of primary tumor locations were small intestine (72% and 81% in the P and O arms). Symptom response at M6 was 9/43 (21%) and 12/45 (27%) in the P and O arms, odds ratio 0.73 (95% CI, 0.27-1.97; p=0.53). Median numbers of D/day and F/2 weeks and change in symptom from baseline to M6 are in Table. Hyperglycemia (11% vs 0%), diarrhea (9% vs 7%), and abdominal pain (2% vs 9%) were the most common grade 3/4 AEs in the P vs O arms in the core phase, and 7 (13%) and 4 (7%) pts discontinued due to AEs. Median investigator-assessed PFS was 11.8 months and 6.8 months in the P and O arms (HR=0.46; p=0.045). Conclusions: P and O showed a similar safety profile except for the higher frequency of hyperglycemia in P. Pts on P had PFS 5 months longer than pts on O (investigator assessment), despite no differences in symptom response rates. These results warrant a large phase III trial to clarify the role of P as a therapy for NET. Clinical trial information: NCT00690430. [Table: see text]

scholarly journals Randomized, open-label, multicenter, phase III study of eribulin versus dacarbazine in patients (pts) with leiomyosarcoma (LMS) and adipocytic sarcoma (ADI).

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA10502-LBA10502 ◽  
Author(s):  
Patrick Schöffski ◽  
Robert G. Maki ◽  
Antoine Italiano ◽  
Hans Gelderblom ◽  
Giovanni Grignani ◽  
...  
Keyword(s):  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Open Label ◽  
Treatment Regimens ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Peripheral Sensory

LBA10502 Background: In a phase II study of pts with advanced soft tissue sarcoma, 32% and 47% of pts with LMS and ADI respectively, treated with the microtubule dynamics inhibitor eribulin achieved progression-free survival (PFS) at the 12 wk timepoint (Schöffski et al. Lancet Oncol. 2011; NCT00413192). Based on these findings, this phase III study (NCT01327885) compared overall survival (OS) in pts with advanced LMS and ADI treated with eribulin or dacarbazine. Methods: Pts aged ≥ 18 yrs with advanced high/intermediate grade LMS or dedifferentiated, myxoid, round cell or pleomorphic variants of ADI incurable by surgery and/or radiotherapy were enrolled. Pts had ECOG status ≤ 2 and had received ≥ 2 standard systemic treatment regimens including an anthracycline. Pts were randomized 1:1 to eribulin (1.4 mg/m2, IV on D1 and D8) or dacarbazine (850–1200 mg/m2, IV on D1) every 21 days until disease progression. Primary endpoint was OS. Secondary endpoints included PFS, PFS rate at Wk 12 and safety. Results: Overall, 452 pts (67% female; 79% < 65 yrs) were randomized (228 eribulin; 224 dacarbazine). Median OS for eribulin and dacarbazine was 13.5 and 11.5 months, respectively (HR = 0.768, 95% CI 0.618–0.954; P= 0.017). PFS was 2.6 months in both arms (HR = 0.877, 95% CI 0.710–1.085; P= 0.229). PFS rate at Wk 12 was 33% and 29% for eribulin and dacarbazine, respectively. In eribulin and dacarbazine arms, respectively, 26% and 14% of pts required dose reductions and 8% and 5% discontinued due to treatment-emergent adverse events (TEAEs). TEAEs were more frequent in eribulin than dacarbazine arm, including neutropenia (44% vs 24%), pyrexia (28% vs 14%), peripheral sensory neuropathy (20% vs 4%) and alopecia (35% vs. 3%); as were TEAEs of grade 3 (63% vs 53%), grade 4 (26% vs 20%), and fatal TEAEs (4% vs 1%). Thrombocytopenia was more frequent in dacarbazine than eribulin arm (28% vs 6%). Conclusions: This phase III trial of eribulin trial met its primary objective of OS benefit in pretreated pts with advanced LMS or ADI. Eribulin had a toxicity profile consistent with prior experience, with no unexpected or new safety findings. Funding Source: Eisai Inc. Clinical trial information: NCT01327885.

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