Outcomes in patients with liver or lung metastatic castration-resistant prostate cancer (mCRPC) treated with the androgen receptor inhibitor enzalutamide: Results from the phase III AFFIRM trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5065-5065 ◽  
Author(s):  
Yohann Loriot ◽  
Karim Fizazi ◽  
Johann Sebastian De Bono ◽  
David Forer ◽  
Mohammad Hirmand ◽  
...  
Keyword(s):  
Overall Survival ◽  
Androgen Receptor ◽  
Lung Metastases ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind Study ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Psa Response

5065 Background: Enzalutamide (ENZA) inhibits multiple steps in the androgen receptor signaling pathway (Tran et al, Science. 2009;324:787). The phase III AFFIRM trial demonstrated that ENZA increased median overall survival (OS) by 4.8 months (P <0.001, HR 0.63) vs placebo (PBO) in post-docetaxel mCRPC patients (pts) (Scher et al, NEJM 2012; 367:1187). Here we assess the effect of ENZA on outcomes in pts with liver or lung metastases in the AFFIRM trial. Methods: The AFFIRM trial was a phase III multinational, randomized, double-blind study in post-docetaxel mCRPC pts. Randomization was 2:1 to ENZA 160 mg/day or PBO, stratified by baseline ECOG and mean pain score. The primary endpoint was overall survival (OS). Radiographic progression-free survival (rPFS) was a key secondary endpoint. PSA response defined as a decline of ≥50% compared to baseline, and soft tissue objective response per RECIST 1.1 were also assessed and reported here. Results: Pts with liver mCRPC comprised 11.5% (92/800) of ENZA pts and 8.5% (34/399) of PBO pts. Pts with lung mCRPC comprised 15.3% (122/800) of ENZA pts and 14.8% (59/399) of PBO pts. The median OS for patients with liver and/or lung mCRPC in the AFFIRM trial was 11.4 months (ENZA: 13.4 months; PBO: 9.5 months). Improved outcomes with ENZA treatment were observed in both liver and lung mCRPC pts. Conclusions: In the phase III AFFIRM trial, pts with lung mCRPC had higher median OS than pts with liver mCRPC. ENZA resulted in higher response rates in both liver and lung mCRPC pts. OS and rPFS were also improved in both pt groups treated with ENZA. Clinical trial information: NCT00974311. [Table: see text]

A hypothesis-generating exploratory analysis of efficacy and safety of abiraterone acetate (AA) in African American (Af Am) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 55-55
Author(s):  
Eleni Efstathiou ◽  
Vasily J. Assikis ◽  
Scott A. North ◽  
John Showel ◽  
Thomas E. Hutson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Safety Profile ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Psa Response ◽  
Grade 3

55 Background: The reported increased prostate cancer lethality in Af Ams has been attributed by some to altered androgen receptor (AR) signaling. We compared toxicity, PSA response, time-to-PSA progression (TTPP), and radiographic progression-free survival (rPFS) in Af Am vs non Af Am pts with CRPC treated with AA + prednisone (P) vs placebo + P. We hypothesized that differences in response to AA may be observed if differences in AR signaling exist in Af Ams. Methods: COU-AA-301 is a randomized double blind study of AA (1000 mg + P 5 mg po BID) vs placebo + P post-docetaxel. Results: TTPP, rPFS, and PSA response rate were higher with AA vs placebo. In Af Am pts, treatment emergent AEs (TEAEs) for AA vs placebo occurred in 96.4% vs 100.0% of pts (50.0% and 66.7%, respectively, grade 3/4); serious TEAEs occurred in 42.9% and 33.3% of pts (28.6% and 26.7%, respectively, grade 3/4). The safety profile of AA appears comparable between the Af Am and overall study populations. Conclusions: Although the small number of Af Am pts in this study precludes formal conclusions regarding efficacy and safety of AA in this pt population, the overall trend suggests these pts experienced clinical benefit from AA with a safety profile comparable to the overall study population. These findings do not appear to support the hypothesis that AR signaling accounts for the increased lethality of prostate cancer seen in Af Ams. Further studies of AA in Af Am pts are planned to understand the potential benefit in this population. Additional efforts are needed to increase participation of Af Am pts in clinical trials. [Table: see text]

ERG rearrangements and association with clinical outcome in patients (pts) receiving abiraterone acetate (AA): Results from the COU-AA-302 study in chemotherapy (chemo)-naïve metastatic castration-resistant prostate cancer (mCRPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5004-5004 ◽  
Author(s):  
Gerhardt Attard ◽  
Johann Sebastian De Bono ◽  
Weimin Li ◽  
Arturo Molina ◽  
Thomas W. Griffin ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Double Blind Study ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Tissue Samples ◽  
Psa Response ◽  
Psa Progression

5004 Background: ERG rearrangements result in androgen receptor-modulated up-regulation of ERG and may predict for AA response in mCRPC. Concordance has been shown between ERG status in archival samples and fresh CRPC biopsies (Attard et al., Cancer Res. 2009;69:2912). In this prospectively defined biomarker sub-study, the association between ERG subtypes and clinical outcome in chemo-naïve mCRPC pts receiving AA was evaluated. Methods: COU-AA-302 is a randomized double blind study of AA (1 g) + prednisone (P) (5 mg BID) vs placebo + P in chemo-naïve mCRPC. Fluorescence in situ hybridization (FISH) assays to evaluate ERG subtypes (Attard et al., Oncogene. 2008;27:253) were conducted on 524 archival prostate tissue samples (365 biopsies, 107 RPEs, 44 TURPs, 3 bone marrows, 5 lymph nodes) from 497 pts. Clinical outcome measures included radiographic progression-free survival (rPFS) (central [CEN] and investigator [INV] reviewed), time to PSA progression (TTPP), and PSA ≥ 50% decline. Cox regression was used to evaluate association with time to event endpoints and Cochran-Mantel-Haenszel for PSA response. Results: 337 of 497 pts with tumor samples had evaluable FISH results. An ERG rearrangement was present in 117 of 337 (35%) pts. 112 pts were class Edel, 50 were 2+Edel (interstitial deletion with duplication of fusion sequences) and 18 were ESplit. A trend for an association with greater improved rPFS (CEN) and TTPP in 2+ Edel pts treated with AA + P vs ERG non-rearranged was observed (22 months [m] vs 16 m [HR: 0.59, 95% CI: 0.30-1.16], p = 0.12, and 14 m vs 8 m [HR: 0.68; 95% CI: 0.41-1.15], p = 0.15, respectively). No differences in 2+ Edel vs ERG non-rearranged were observed in the P-alone arm. No association between any ERG sub-class and either rPFS [INV] or PSA ≥ 50% decline in either treatment arm was observed. Conclusions: This represents the largest study to date to molecularly characterize CRPC pts participating in a therapeutic phase 3 trial. These data suggest that chemo-naïve mCRPC pts with a 2+ Edel rearrangement may derive a slightly greater benefit from AA and P than other pts. Clinical trial information: NCT00887198.

Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group

2007 ◽  
Vol 25 (15) ◽  
pp. 1960-1966 ◽  
Author(s):  
Malcolm J. Moore ◽  
David Goldstein ◽  
John Hamm ◽  
Arie Figer ◽  
Joel R. Hecht ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Pancreatic Tumors ◽  
Double Blind ◽  
Phase Iii Trial

PurposePatients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer.Patients and MethodsPatients were randomly assigned 1:1 to receive standard gemcitabine plus erlotinib (100 or 150 mg/d orally) or gemcitabine plus placebo in a double-blind, international phase III trial. The primary end point was overall survival.ResultsA total of 569 patients were randomly assigned. Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio (HR) of 0.82 (95% CI, 0.69 to 0.99; P = .038, adjusted for stratification factors; median 6.24 months v 5.91 months). One-year survival was also greater with erlotinib plus gemcitabine (23% v 17%; P = .023). Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 (95% CI, 0.64 to 0.92; P = .004). Objective response rates were not significantly different between the arms, although more patients on erlotinib had disease stabilization. There was a higher incidence of some adverse events with erlotinib plus gemcitabine, but most were grade 1 or 2.ConclusionTo our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.

Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small cell lung cancer (NSCLC): A randomized, double-blind phase III trial (ZODIAC)

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. CRA8003-CRA8003 ◽  
Author(s):  
R. S. Herbst ◽  
Y. Sun ◽  
S. Korfee ◽  
P. Germonpré ◽  
N. Saijo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Positive Trend ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Double Blind

CRA8003 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. Addition of vandetanib to docetaxel (doc) prolonged progression-free survival (PFS) in a randomized phase II study in patients (pts) with previously treated NSCLC (Heymach et al, JCO, 2007). Methods: The primary objective was to determine whether vandetanib 100 mg/day + doc 75 mg/m2 every 21 days (max 6 cycles) prolonged PFS vs placebo + doc. Secondary endpoints included overall survival, objective response rate (ORR), time to deterioration of symptoms (TDS) and safety. Efficacy and safety in females were assessed as a co-primary analysis population. Eligibility criteria included stage IIIB/IV NSCLC, PS 0–1, and previous first-line chemotherapy. Results: Between May 2006 and April 2008, 1,391 pts (mean age, 58 years; 30% female; 25% squamous; 10% brain mets) were randomized to vandetanib + doc (n=694) or placebo + doc (n=697). Baseline characteristics were similar in both arms. Median duration of follow-up was 12.8 months, with 87% patients progressed and 59% dead. Addition of vandetanib to doc showed a statistically significant improvement in PFS vs doc (hazard ratio [HR] 0.79, 97.58% CI 0.70–0.90; P<0.001), and a similar advantage in females (HR 0.79; P=0.024). Significant advantages for vandetanib + doc were also seen for ORR (17% vs 10%, P<0.001) and TDS (HR 0.78, P=0.002; FACT-L Lung Cancer Subscale). Overall survival showed a positive trend for vandetanib + doc that was not statistically significant (HR 0.91, 97.52% CI 0.78–1.07; P=0.196). The adverse event (AE) profile was consistent with that previously observed for vandetanib in NSCLC. Common AEs occurring more frequently in the vandetanib arm included diarrhea (42% vs 33%), rash (42% vs 24%) and neutropenia (32% vs 27%). Nausea (23% vs 32%), vomiting (16% vs 21%) and anemia (10% vs 15%) were less frequent in the vandetanib arm. The incidence of protocol-defined QTc prolongation was <2% in pts receiving vandetanib. Conclusions: The study met its primary objective of PFS prolongation with vandetanib + doc vs doc. Vandetanib is the first oral targeted therapy in phase III trials to show significant evidence of clinical benefit when added to standard chemotherapy in NSCLC. [Table: see text]

Overall survival (OS) analysis of a phase II randomized controlled trial (RCT) of a poxviral-based PSA targeted immunotherapy in metastatic castration-resistant prostate cancer (mCRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5013-5013
Author(s):  
P. W. Kantoff ◽  
T. Schuetz ◽  
B. A. Blumenstein ◽  
M. M. Glode ◽  
D. Bilhartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Viral Vectors ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Gm Csf

5013 Background: Therapeutic poxviral vaccines for prostate cancer are safe with preliminary evidence of clinical benefit in phase I/II studies. PROSTVAC-VF (PV) comprises 2 recombinant viral vectors (Vaccinia and Fowlpox), each encoding transgenes for prostate specific antigen (PSA) and 3 immune costimulatory molecules (B7.1, ICAM-1, and LFA3: TRICOM). PV is administered subcutaneously in a heterologous prime-boost regimen with concurrent low-dose GM-CSF. Methods: 122 patients (pts) were treated in a multi-center, double-blind, RCT of a vaccination series. Pts were randomized 2:1 to PV + GM-CSF vs. placebo empty vector + control saline injections (C). Vaccinia-based vector was used for priming followed by 6 planned Fowlpox-based vector boosts. The trial completed enrollment in July 2005. Eligible pts had metastatic disease, a rising PSA despite castrate testosterone levels, and a Gleason score of ≤7. Pts with a history of prior chemotherapy use, visceral metastasis, or narcotic use were excluded. The 1º endpoint was progression free survival (PFS), with progression defined as 2 new lesions on bone scan or RECIST-defined progression. Vaccination was discontinued after progression. Results: 82 pts received PV and 40 received C. Pt characteristics were similar (means): age (72PV/76C), PSA (134PV/188C), Alk-Phos (142PV/159C), LDH (207PV/218C), Hgb (13PV/13C), and number bone metastatic sites (5.3PV/6.5C). Mean number of vaccinations was 5.4 PV and 5.3 C. PFS was similar in the 2 groups (p = 0.56). However, at 3 years post study, PV patients had a better overall survival than C patients (25 alive, 30%, PV, versus 7 alive, 17%, C) and a longer median survival (24.5 months PV, versus 16 months C); estimated hazard ratio 0.6 (95% CI 0.4–0.9); stratified log rank p = 0.016. Conclusions: In a RCT, PV immunotherapy was associated with an 8.5 month improvement in median OS in men with mCRPC. These data provide evidence of prolonged anti-tumor activity, but need to be confirmed in a larger phase III study. [Table: see text]

Updated results from BELLINI, a phase III study of venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8509-8509 ◽  
Author(s):  
Shaji Kumar ◽  
Simon J. Harrison ◽  
Michele Cavo ◽  
Javier de La Rubia ◽  
Rakesh Popat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind Study ◽  
Double Blind ◽  
Refractory Multiple Myeloma ◽  
Grade 3 ◽  
D 20

8509 Background: Venetoclax (Ven) is a selective, potent, oral BCL-2 inhibitor. In the Phase 3 BELLINI trial, addition of Ven to bortezomib (B) + dexamethasone (d) significantly improved response rates and progression-free survival (PFS) vs placebo (Pbo) and showed significant efficacy in patients (pts) with either t(11;14) or BCL2high gene expression. Here we present updated safety and efficacy data from the prespecified second interim overall survival (OS) analysis. Methods: In this multicenter, randomized, double-blind study (NCT02755597), pts with relapsed/refractory multiple myeloma (RRMM) with 1-3 prior lines of therapy were randomized 2:1 to Ven (800 mg) or Pbo in combination with B (1.3 mg/m2) and d (20 mg). The primary endpoint was PFS; key secondary endpoints included overall response and overall survival (OS). Results: 291 pts were randomized; 194 to Ven, 97 to Pbo. Pt characteristics were well balanced among arms. In the Ven arm, median age was 66, 17% had high-risk cytogenetics, 11% had t(11;14), and 34% had BCL2high gene expression. As of 13 Sept 2019, 59 pts were still on study, 45 (23%) Ven vs 14 (14%) Pbo. At a median follow-up of 28.6 months, there were 64 (33%) deaths in the Ven arm vs 24 (25%) in Pbo. At the initial data cutoff (26 Nov 2018), PFS HR was 0.63 (0.44,0.90) and OS HR was 2.03 (1.04,3.95). Table shows updated PFS and OS. Most common treatment-emergent adverse events (TEAEs) with Ven were diarrhea (59%), nausea (37%), and constipation (35%). Most common grade 3/4 AEs (Ven/Pbo) were neutropenia (21%/8%), thrombocytopenia (15%/30%), anemia (16%/15%), diarrhea (15%/12%), and pneumonia (18%/13%). Serious AEs occurred in 54% Ven and 52% Pbo pts. 24% discontinued Ven due to AEs vs 12% Pbo. There were 14 treatment-emergent deaths in the Ven arm and 1 in Pbo. Conclusions: The addition of Ven to Bd significantly improves PFS but resulted in increased mortality vs Pbo in the total population. Greatest PFS improvement with Ven was observed in pts with t(11;14) or BCL2high gene expression, where Ven shows a favorable benefit-risk profile. The study continues for final OS analysis. Clinical trial information: NCT02755597 . [Table: see text]

scholarly journals Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1284
Author(s):  
Nicolas Delanoy ◽  
Debbie Robbrecht ◽  
Mario Eisenberger ◽  
Oliver Sartor ◽  
Ronald de Wit ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Post Hoc Analysis ◽  
Psa Response ◽  
Phase Iii Study ◽  
Psa Progression ◽  
Previously Treated ◽  
Post Hoc

Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. Conclusions: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.

Phase III Trial of Gemcitabine Plus Tipifarnib Compared With Gemcitabine Plus Placebo in Advanced Pancreatic Cancer

2004 ◽  
Vol 22 (8) ◽  
pp. 1430-1438 ◽  
Author(s):  
E. Van Cutsem ◽  
H. van de Velde ◽  
P. Karasek ◽  
H. Oettle ◽  
W.L. Vervenne ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Survival Rates ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Free Survival

Purpose To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer. Patients and Methods This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m2 intravenously weekly × 7 for 8 weeks, then weekly × 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life. Results Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P = .75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade ≥ 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups. Conclusion The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.

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]

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]

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