Phase III study of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): The ARCHES trial.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 687-687 ◽  
Author(s):  
Andrew J. Armstrong ◽  
Russell Zelig Szmulewitz ◽  
Daniel Peter Petrylak ◽  
Arnauld Villers ◽  
Arun Azad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
High Volume ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3

687 Background: ENZA, a potent androgen receptor inhibitor, has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). Efficacy of ENZA with ADT in men with mHSPC is unknown. Methods: ARCHES is a multinational, double-blind, phase 3 study (NCT02677896). Patients (pts) with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel therapy. Primary endpoint was radiographic progression-free survival (rPFS) assessed centrally or death within 24 weeks of treatment discontinuation. Secondary endpoints included time to prostate-specific antigen (PSA) progression, PSA and radiographic responses and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n=574) or PBO (n=576); baseline characteristics were balanced between groups. Overall, 67% had distant metastasis at initial diagnosis; 63% had high volume disease, 18% had prior docetaxel. Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); similar significant improvements in rPFS were reported in prespecified subgroups of disease volume, pattern of spread, region and prior docetaxel (HRs 0.24–0.53). Secondary endpoints improved with ENZA + ADT (Table); OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs PBO + ADT in men with mHSPC, with a preliminary safety analysis that appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Acknowledgements: Medical writing and editing assistance was provided by Stephanie Rippon, MBio, and Lauren Smith from Complete HealthVizion, funded by the study sponsors. This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. Clinical trial information: NCT02677896. [Table: see text]

ARCHES: Efficacy of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5048-5048
Author(s):  
Andrew J. Armstrong ◽  
Russell Zelig Szmulewitz ◽  
Daniel Peter Petrylak ◽  
Jeffrey M. Holzbeierlein ◽  
Arnauld Villers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
High Volume ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Prior Therapy ◽  
Castration Resistant ◽  
Secondary Endpoints ◽  
Grade 3

5048 Background: ENZA has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). ARCHES assessed the efficacy of ENZA with ADT in men with mHSPC, including pre-specified subgroups based on prior therapy. Methods: ARCHES, a multinational, double-blind, Phase 3 study (NCT02677896), randomized patients (pts) with mHSPC 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel (doce) use. Primary endpoint was radiographic progression-free survival (rPFS; centrally assessed radiographic progression or death within 24 weeks of treatment discontinuation). Secondary endpoints included time to initiation of new antineoplastic therapy and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n = 574) or PBO (n = 576). Overall, 63% had high-volume disease, 18% had prior doce, and 91% had prior ADT or orchiectomy (orch). Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); significant improvements in rPFS were also reported in prior treatment subgroups. Secondary endpoints improved with ENZA + ADT (Table), with no significant impact in time to deterioration in urinary symptoms. OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs. 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs. PBO + ADT in men with mHSPC. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Clinical trial information: NCT02677896. [Table: see text]

Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

2017 ◽  
Vol 35 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Tomasz M. Beer ◽  
Eugene D. Kwon ◽  
Charles G. Drake ◽  
Karim Fizazi ◽  
Christopher Logothetis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Castration Resistant ◽  
Grade 3

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.

Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial

2016 ◽  
Vol 34 (18) ◽  
pp. 2098-2106 ◽  
Author(s):  
David F. Penson ◽  
Andrew J. Armstrong ◽  
Raoul Concepcion ◽  
Neeraj Agarwal ◽  
Carl Olsson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Beneficial Effects ◽  
Castration Resistant

Purpose Enzalutamide, a potent oral androgen receptor inhibitor, improves survival in men with metastatic castration-resistant prostate cancer (CRPC) before and after chemotherapy. Bicalutamide, a nonsteroidal antiandrogen, is widely used to treat men with nonmetastatic or metastatic CRPC. The efficacy and safety of these drugs were compared in this randomized, double-blind, phase II study of men with CRPC. Patients and Methods A total of 396 men with nonmetastatic (n = 139) or metastatic (n = 257) CRPC were randomly assigned to enzalutamide 160 mg per day (n = 198) or bicalutamide 50 mg per day (n = 198). Androgen deprivation therapy was continued in both arms. The primary end point was progression-free survival (PFS). Results Enzalutamide reduced the risk of progression or death by 76% compared with bicalutamide (hazard ratio [HR], 0.24; 95% CI, 0.18 to 0.32; P < .001). Median PFS was 19.4 months with enzalutamide versus 5.7 months with bicalutamide. Enzalutamide resulted in significant improvements in all key secondary end points: time to prostate-specific antigen progression (HR, 0.19; 95% CI, 0.14 to 0.26; P < .001); proportion of patients with a ≥ 50% prostate-specific antigen response (81% v 31%; P < .001); and radiographic PFS in metastatic patients (HR, 0.32; 95% CI, 0.21 to 0.50; P < .001). Beneficial effects with enzalutamide were observed in both nonmetastatic and metastatic subgroups. The observed adverse event profile was consistent with that from phase III enzalutamide trials. Conclusion Enzalutamide significantly reduced risk of prostate cancer progression or death compared with bicalutamide in patients with nonmetastatic or metastatic CRPC.

Phase III, Randomized, Placebo-Controlled Study of Docetaxel in Combination With Zibotentan in Patients With Metastatic Castration-Resistant Prostate Cancer

2013 ◽  
Vol 31 (14) ◽  
pp. 1740-1747 ◽  
Author(s):  
Karim Fizazi ◽  
Celestia S. Higano ◽  
Joel B. Nelson ◽  
Martin Gleave ◽  
Kurt Miller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Points ◽  
Castration Resistant ◽  
Endothelin A

PurposeAs part of the ENTHUSE (Endothelin A Use) program, the efficacy and safety of zibotentan (ZD4054), an oral specific endothelin A receptor antagonist, has been investigated in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (CRPC).Patients and MethodsIn this randomized, double-blind, placebo-controlled, phase III study, patients received intravenous docetaxel 75 mg/m2on day 1 of 21-day cycles plus oral zibotentan 10 mg or placebo once daily. The primary end point was overall survival (OS). Secondary end points included time to pain and prostate-specific antigen (PSA) progression, pain and PSA response, progression-free survival, health-related quality of life, and safety.ResultsA total of 1,052 patients received study treatment (docetaxel-zibotentan, n = 524; docetaxel-placebo, n = 528). At the time of data cutoff, there had been 277 and 280 deaths, respectively. There was no difference in OS for patients receiving docetaxel-zibotentan compared with those receiving docetaxel-placebo (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P = .963). No significant differences were observed on secondary end points, including time to pain progression (median 9.3 v 10.0 months, respectively) or pain response (odds ratio, 0.84; 95% CI, 0.61 to 1.16; P = .283). The median time to death was 20.0 and 19.2 months for the zibotentan and placebo groups, respectively. The most commonly reported adverse events in zibotentan-treated patients were peripheral edema (52.7%), diarrhea (35.4%), alopecia (33.9%), and nausea (33.3%).ConclusionDocetaxel plus zibotentan 10 mg/d did not result in a significant improvement in OS compared with docetaxel plus placebo in patients with metastatic CRPC.

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]

scholarly journals Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

2016 ◽  
Vol 9 (2) ◽  
pp. 506-515
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vamshi Krishna Muddu ◽  
Vijay Maruti Patil ◽  
Kumar Prabhash
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Retrospective Data Analysis ◽  
Grade 3 ◽  
Named Patient Programme

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27) under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80) and progression-free survival was 2.67 months (1.07–20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

Low-Dose Docetaxel Combined with Dexamethasone Is Feasible for Patients with Castration-Resistant Prostate Cancer

Chemotherapy ◽  
2015 ◽  
Vol 61 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Noriyoshi Miura ◽  
Nozomu Tanji ◽  
Yutaka Yanagihara ◽  
Terutaka Noda ◽  
Seiji Asai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Low Dose ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Hematological Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Gastric Bleeding ◽  
Castration Resistant ◽  
Analgesic Agents ◽  
Grade 3

Aim: Docetaxel-based chemotherapy against castration-resistant prostate cancer (CRPC) has recently been shown to be effective and tolerable. The objective of this study was to retrospectively evaluate the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. Methods: Thirty-seven CRPC patients were administered a treatment regimen consisting of 50 mg/m2 docetaxel once every 3-4 weeks and 1 mg dexamethasone daily at our institution, between November 2004 and April 2014. Results: Twenty-four patients (65%) had a decrease in serum prostate-specific antigen (PSA) >50%. The median overall survival (OS) and PSA progression-free survival were 26.2 and 10.0 months, respectively. Ten of 12 patients (83%) taking analgesic agents reduced their intake because of decreased pain levels. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 octogenarian patients, 1 due to gastric bleeding and the other due to infective endocarditis. Conclusion: Low-dose docetaxel in combination with dexamethasone is feasible in Japanese CRPC patients. Hematological toxicity is less than that seen with standard docetaxel therapy, but it is necessary to monitor patients for severe nonhematological toxicities, particularly very elderly patients.

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]

Comparison of two doses of cabazitaxel plus prednisone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel (D)-containing regimen.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4692-TPS4692 ◽  
Author(s):  
Mario A. Eisenberger ◽  
Anne-Claire Hardy-Bessard ◽  
Loic Mourey ◽  
Paul N. Mainwaring ◽  
Daniel Ford ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Measurable Disease ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps

TPS4692^ Background: The phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for cabazitaxel (Cbz) + prednisone (P;CbzP) (25 mg/m2 IV Q3W/10 mg PO QD) vs mitoxantrone (M) + P (MP) (median OS 15.1 vs 12.7 mos; HR 0.70; P < 0.0001) in pts with mCRPC (also known as hormone-refractory prostate cancer) previously treated with a D-containing regimen. CbzP is approved by the FDA, EMA and other health authorities for the treatment of pts with mCRPC that has progressed after a D-containing regimen. Cbz toxicity is consistent with other taxanes; compared with M, more hematologic toxicities are reported (primarily Grade 3–4 neutropenia). Phase I/II studies identified 20 and 25 mg/m2 as recommended doses; 25 mg/m2 was selected for the phase III TROPIC study. As pooled data show Grade 3–4 neutropenia incidence is lower with Cbz < 25 mg/m2 (61%) vs ≥ 25 mg/m2 (74%), it is of interest to assess if reducing the Cbz approved dose in mCRPC lessens hematologic toxicity and is non-inferior in terms of efficacy. Methods: PROSELICA (NCT01308580) is a randomized, open-label, multinational, phase III study comparing 20 mg/m2 and 25 mg/m2 Cbz for efficacy and tolerability. Pts with a life expectancy > 6 mos, ECOG PS ≤ 2, histologically/cytologically confirmed metastatic prostate adenocarcinoma resistant to hormone therapy and previously treated with a D-containing regimen are eligible. Pts are randomized 1:1 to receive Cbz 20 mg/m² or 25 mg/m² IV Q3W + P 10 mg PO QD, treated until disease progression, unacceptable toxicity or withdrawal of consent (max 10 cycles), and stratified according to ECOG PS, measurable disease (yes/no) and region. The primary endpoint is OS (non-inferiority design). Secondary endpoints include safety, progression-free survival (PCWG2 criteria), PSA and pain progression and response, tumor response in pts with measurable disease and health-related quality of life. Cbz PK and pharmacogenomics will be assessed in pt subgroups. Planned enrollment is 1,200 pts. Study start was in May 2011; as of Jan 2012, 270 pts had been enrolled. The first DMC meeting recommended continuing the study without change.

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]

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