scholarly journals Randomized Phase III Study of FOLFOX Alone or With Pegilodecakin as Second-Line Therapy in Patients With Metastatic Pancreatic Cancer That Progressed After Gemcitabine (SEQUOIA)

2021 ◽  
pp. JCO.20.02232
Author(s):  
J. Randolph Hecht ◽  
Sara Lonardi ◽  
Johanna Bendell ◽  
Hao-Wen Sim ◽  
Teresa Macarulla ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Second Line ◽  
Response Evaluation ◽  
Phase Iii Study ◽  
Gemcitabine Refractory

PURPOSE SEQUOIA compared efficacy and safety of adding pegilodecakin (PEG), a pegylated recombinant human interleukin (IL)-10, with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) in patients following progression on first-line gemcitabine-containing therapy with metastatic pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS SEQUOIA, a randomized, global phase III study, compared FOLFOX with PEG + FOLFOX as second line in gemcitabine-refractory PDAC. Patients were randomly assigned 1:1 (PEG + FOLFOX:FOLFOX) and stratified by prior gemcitabine and region. Eligible patients had only one prior gemcitabine-containing treatment. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), response evaluation per Response Evaluation Criteria in Solid Tumor (RECIST) 1.1, and safety. Exploratory analyses included biomarkers related to immune activation. RESULTS Between March 1, 2017, and September 9, 2019, 567 patients were randomly assigned PEG + FOLFOX (n = 283) or FOLFOX (n = 284). Most (94.7%) patients received prior gemcitabine plus nab paclitaxel. OS was similar comparing PEG + FOLFOX versus FOLFOX (median: 5.8 v 6.3 months; hazard ratio = 1.045; 95% CI, 0.863 to 1.265). Also, PFS (median 2.1 v 2.1 months; hazard ratio = 0.981; 95% CI, 0.808 to 1.190) and objective response rate (4.6% v 5.6%) were similar between the treatment arms. Most common (≥ 35%) treatment-emergent adverse events in PEG + FOLFOX versus FOLFOX were thrombocytopenia (55% v 20%), anemia (40% v 16%), fatigue (61% v 45%), neutropenia (39% v 28%), abdominal pain (37% v 29%), nausea (45% v 41%), neuropathy (37% v 38%), and decreased appetite (35% v 31%). Exploratory analyses revealed increases in total IL-18, interferon (IFN)-γ, and granzyme B and decreases in transforming growth factor (TGF)-β with the addition of PEG. CONCLUSION PEG added to FOLFOX did not improve efficacy in advanced gemcitabine-refractory PDAC. Safety findings were consistent as previously observed from PEG with chemotherapy; toxicity was manageable and tolerable. Exploratory pharmacodynamic results were consistent with immunostimulatory signals of the IL-10R pathway.

Final results from study 181: Randomized phase III study of FOLFIRI with or without panitumumab (pmab) for the treatment of second-line metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 387-387 ◽  
Author(s):  
Alberto F. Sobrero ◽  
Marc Peeters ◽  
Timothy Jay Price ◽  
Yevhen Hotko ◽  
Andres Cervantes-Ruiperez ◽  
...  
Keyword(s):  
Descriptive Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Second Line ◽  
Primary Analysis ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Event Rates

387 Background: In the primary analysis of study 181, pmab+FOLFIRI significantly improved progression-free survival (PFS) vs FOLFIRI as second-line therapy in patients (pts) with wild-type (WT) KRAS mCRC. Here, we report the results of a prespecified final descriptive analysis planned for 30 months (mos) after the last pt was enrolled. Methods: Pts were randomised 1:1 to pmab 6.0 mg/kg Q2W+FOLFIRI (Arm 1) vs FOLFIRI alone (Arm 2). Pts had one prior fluoropyrimidine-based chemotherapy regimen for mCRC and ECOG 0-2. The co-primary endpoints were PFS (central assessment) and OS, and were independently tested. Secondary endpoints included objective response rate (ORR), and safety. KRAS status was determined by a blinded central lab. Results: 1,186 pts were randomised and received treatment (tx): 591 in Arm 1, 595 In Arm 2. 1,083/1,186 pts (91%) had KRAS results. Adverse event rates were consistent with the primary analysis. Results are shown in the table . Conclusions: In Arm 1, PFS (standard and on-treatment definition) and ORR were improved, and there was a trend toward improved OS in pts with WT KRAS mCRC. The large proportion of pts receiving post-progression anti-EGFR therapy may have affected the ability to observe a difference in OS between the tx arms. In pts with MT KRAS there was no difference in efficacy. KRAS testing is critical to select appropriate pts for tx with pmab. [Table: see text]

Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study.

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA4001-LBA4001
Author(s):  
Ian Chau ◽  
Yuichiro Doki ◽  
Jaffer A. Ajani ◽  
Jianming Xu ◽  
Lucjan Wyrwicz ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Endpoints ◽  
First Results ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Previously Treated Patients

LBA4001 Background: NIVO demonstrated superior overall survival (OS) vs chemo in previously treated patients (pts) with ESCC (ATTRACTION-3). We report OS and progression-free survival (PFS) from CheckMate 648, the first global phase III study to evaluate both an immuno-oncology (I-O)/chemo combination and an I-O/I-O combination in advanced ESCC. Methods: Adults with previously untreated, unresectable advanced, recurrent or metastatic ESCC were enrolled regardless of tumor cell PD-L1 expression. Pts were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), or chemo alone. Primary endpoints for both comparisons were OS and PFS per blinded independent central review (BICR) in pts with tumor cell PD-L1 ≥ 1%. Hierarchically tested secondary endpoints included OS and PFS in all randomized pts. Results: 970 pts were randomized to NIVO + chemo, NIVO + IPI, and chemo arms (49% with tumor cell PD-L1 ≥ 1%). With 13 months (mo) minimum follow-up, NIVO + chemo and NIVO + IPI led to statistically significant improvement in OS vs chemo in pts with tumor cell PD-L1 ≥ 1% and all randomized pts (Table). Statistically significant PFS benefit was also observed for NIVO + chemo vs chemo (HR 0.65 [98.5% CI 0.46–0.92]; P = 0.0023) in pts with tumor cell PD-L1 ≥ 1%. PFS in NIVO + IPI vs chemo in pts with tumor cell PD-L1 ≥ 1% did not meet the prespecified boundary for significance. The objective response rate (per BICR) was 53% (NIVO + chemo), 35% (NIVO + IPI), and 20% (chemo) in pts with tumor cell PD-L1 ≥ 1% and in all randomized pts was 47%, 28%, and 27%, respectively; longer median (95% CI) duration of response was observed vs chemo for pts with tumor cell PD-L1 ≥ 1%: 8.4 (6.9–12.4), 11.8 (7.1–27.4), and 5.7 (4.4–8.7) mo and for all randomized pts: 8.2 (6.9–9.7), 11.1 (8.3–14.0), and 7.1 (5.7–8.2) mo, respectively. No new safety signals were identified (Table). Conclusions: NIVO plus chemo and NIVO plus IPI both demonstrated superior OS vs chemo, along with durable objective responses and acceptable safety, in pts with advanced ESCC, and each represents a potential new 1L treatment option. Clinical trial information: NCT03143153. [Table: see text]

Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine

2017 ◽  
Vol 35 (30) ◽  
pp. 3433-3439 ◽  
Author(s):  
George D. Demetri ◽  
Patrick Schöffski ◽  
Giovanni Grignani ◽  
Jean-Yves Blay ◽  
Robert G. Maki ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Eribulin Mesylate ◽  
Systemic Treatments ◽  
Phase Iii Study

Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included. Patients with Eastern Cooperative Oncology Group performance status ≤ 2 and two or more prior systemic treatment regimens, including one with anthracycline, were randomly assigned 1:1 to receive eribulin mesylate (1.4 mg/m2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m2 intravenously on day 1) every 21 days. OS, progression-free survival (PFS), and safety were analyzed. Results In the LPS subgroup, OS was significantly improved: 15.6 versus 8.4 months (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < .001) with eribulin versus dacarbazine, respectively. Longer OS with eribulin was observed in all LPS histologic subtypes and in all geographic regions evaluated. PFS was also improved with eribulin versus dacarbazine (2.9 v 1.7 months, respectively; hazard ratio, 0.52; 95% CI, 0.35 to 0.78; P = .0015). Adverse events were similar between arms. Conclusion In patients with previously treated LPS, eribulin was associated with significantly superior OS and PFS compared with dacarbazine. Eribulin represents an important treatment option for patients with LPS, a sarcoma subtype for which limited effective systemic treatments are available. Further studies are justified to explore the role of eribulin in earlier lines of therapy as well as in combination with other agents.

REVEL: A randomized, double-blind, phase III study of docetaxel (DOC) and ramucirumab (RAM; IMC-1121B) versus DOC and placebo (PL) in the second-line treatment of stage IV non-small cell lung cancer (NSCLC) following disease progression after one prior platinum-based therapy.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA8006-LBA8006 ◽  
Author(s):  
Maurice Perol ◽  
Tudor-Eliade Ciuleanu ◽  
Oscar Arrieta ◽  
Kumar Prabhash ◽  
Konstantinos N. Syrigos ◽  
...  
Keyword(s):  
Disease Progression ◽  
Primary Endpoint ◽  
Objective Response ◽  
Pulmonary Hemorrhage ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Double Blind

LBA8006^ Background: RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The REVEL study evaluated the efficacy and safety of RAM+DOC vs. PL+DOC (DOC) in patients (pts) with stage IV nonsquamous (NSQ) and squamous (SQ) NSCLC after platinum-based therapy. Methods: Pts with NSQ and SQ stage IV NSCLC were randomized 1:1 (stratified by sex, region, ECOG PS, and prior maintenance therapy) to receive DOC 75 mg/m2 in combination with either RAM 10 mg/kg or PL on day 1 of a 21-day cycle until disease progression, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary efficacy endpoints included progression-free survival (PFS), and objective response rate (ORR). Results: Between Dec 2010 and Feb 2013, 1,253 pts (26.2% SQ) were randomized (RAM+DOC: 628; DOC: 625). Pt characteristics were balanced between arms. ORR was 22.9% for RAM+DOC and 13.6% for DOC (P<0.001). The hazard ratio (HR) for PFS was 0.762 (P<0.0001); median PFS was 4.5 months (m) for RAM+DOC vs. 3.0m for DOC. REVEL met its primary endpoint; the OS HR was 0.857 (95% CI 0.751, 0.98; P=0.0235); median OS was 10.5m for RAM+DOC vs. 9.1m for DOC. OS was longer for RAM+DOC in most pt subgroups, including SQ and NSQ histology. Grade ≥3 adverse events (AEs) occurring in >5% of pts on RAM+DOC were neutropenia (34.9% vs. 28.0%), febrile neutropenia (15.9% vs. 10.0%), fatigue (11.3% vs. 8.1%), leukopenia (8.5% vs. 7.6%), hypertension (5.4% vs. 1.9%), and pneumonia (5.1% vs. 5.8%). Grade 5 AEs were comparable between arms (5.4% vs. 5.8%), as was pulmonary hemorrhage (any grade; all pts: 2.1% vs. 1.6%; SQ pts: 3.8% vs. 2.4%). Conclusions: REVEL demonstrated a statistically significant improvement in ORR, PFS, and OS for RAM+DOC vs DOC in NSCLC pts with stage IV NSCLC as second-line treatment after platinum-based therapy. Benefits were similar in NSQ and SQ pts, and no unexpected AEs were identified. Clinical trial information: NCT01168973.

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]

NEJ026: Final overall survival analysis of bevacizumab plus erlotinib treatment for NSCLC patients harboring activating EGFR-mutations.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9506-9506 ◽  
Author(s):  
Makoto Maemondo ◽  
Tatsuro Fukuhara ◽  
Haruhiro Saito ◽  
Naoki Furuya ◽  
Kana Watanabe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Analysis ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Line Treatment ◽  
Second Line ◽  
Overall Survival Analysis

9506 Background: In NEJ026, a phase III trial comparing bevacizumab plus erlotinib (BE) to erlotinib monotherapy (E) for EGFR-mutated non-small-cell lung cancer (NSCLC), we demonstrated the progression-free survival (PFS) of BE was significantly superior to E (Saito et al. Lancet Oncol. 2019 May;20(5):625-635.). However overall survival analysis were immature at the cutoff date. Methods: Chemotherapy-naïve pts with advanced non-squamous NSCLC harboring EGFR-mutation were randomly assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). The primary endpoint was PFS. Secondary endpoints were OS, RR, safety, and QoL. Results: The 226 pts were assigned to BE (n=112) and E (n=114). For the follow-up OS analysis, the data cut-off date was 30 November 2019. Median follow up time was 39.2 months. Median OS was 50.7 months (95% CI, 37.3 months to not reached) with BE and 46.2 months (95% CI, 38.2 months to not reached) with E (hazard ratio, 1.00; 95% CI, 0.68 to 1.48). Twenty-nine patients (25.9%) in BE and twenty-six patients (23.2%) in E were treated by osimertinib as second line treatment. The median survival time between enrollment and progressive disease of second-line treatment (median PFS2) was 28.6 months (95% CI, 22.1 months to 35.9) with BE and 24.3 months (95% CI, 20.4 months to 29.1 months) with E (hazard ratio, 0.80; 95% CI, 0.59 to 1.10). In both arms, the median OS of patients with osimertinib second-line treatment were longer than other second-line chemotherapy groups [50.7 months (95% CI, 38.0 months to 50.7 months) vs 40.1 months (95% CI, 29.5 months to not reached), (hazard ratio, 0.645; 95% CI, 0.40 to 1.03), respectively. Conclusion: The additional effect of bevacizumab on erlotinib monotherapy for NSCLC with EGFR mutations gradually decreased in the order of PFS2 and survival, with no significant differences. Clinical trial information: UMIN000017069 .

Response-Independent Survival Benefit in Metastatic Colorectal Cancer: A Comparative Analysis of N9741 and AVF2107

2008 ◽  
Vol 26 (2) ◽  
pp. 183-189 ◽  
Author(s):  
Axel Grothey ◽  
Eric E. Hedrick ◽  
Robert D. Mass ◽  
Somnath Sarkar ◽  
Sam Suzuki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Tumor Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Phase Iii Study

PurposeIn the phase III study AVF2107g, bevacizumab (BV) demonstrated a survival benefit when added to irinotecan, fluorouracil, and leucovorin (IFL) in first-line metastatic colorectal cancer (mCRC). In a parallel phase III study, Intergroup N9741, oxaliplatin plus fluorouracil and leucovorin (FOLFOX) also demonstrated a survival benefit compared with IFL. As these two superior therapies have differing mechanisms of action, we explored whether the improved survival associated with the superior therapy was dependent on tumor response.Patients and MethodsFor these retrospective, exploratory analyses, patients were defined as responders or nonresponders by whether complete or partial response was achieved with first-line therapy.ResultsCompared with IFL alone, BV plus IFL and FOLFOX each demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) regardless of objective tumor response. BV-treated nonresponders had a hazard ratio (HR) of 0.63 (P = .0001) for PFS and 0.76 (P = .0188) for OS compared with IFL-treated nonresponders. FOLFOX-treated nonresponders had an HR of 0.75 (P = .0029) for PFS and 0.74 (P = .0030) for OS compared with IFL-treated nonresponders.ConclusionIn both AVF2107g and N9741, objective response did not predict the magnitude of PFS or OS benefit from the superior therapy; nonresponders, despite a poorer prognosis than responders, achieved extended PFS and OS from BV plus IFL or FOLFOX compared with IFL. On the basis of these data, tumor response in metastatic colorectal cancer is not a necessary factor for a therapy to provide benefit to an individual patient.

Randomized phase III study of irinotecan (CPT-11) versus weekly paclitaxel (wPTX) for advanced gastric cancer (AGC) refractory to combination chemotherapy (CT) of fluoropyrimidine plus platinum (FP): WJOG4007 trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4002-4002 ◽  
Author(s):  
Shinya Ueda ◽  
Shuichi Hironaka ◽  
Hirofumi Yasui ◽  
Tomohiro Nishina ◽  
Masahiro Tsuda ◽  
...  
Keyword(s):  
Adverse Events ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Standard Regimen ◽  
Phase Iii Trials ◽  
Phase Iii Study ◽  
Third Line

4002 Background: A combination CT of FP has been regarded as the standard first-line treatment for AGC. Although two randomized trials showed a survival benefit of second-line CT (CPT-11 or docetaxel) compared with best supportive care, no standard regimen has been established. In Japan, wPTX has been used more frequently than docetaxel as the second‑line CT. The objective of this study was to compare CPT-11 with wPTX in patients (pts) with AGC refractory to FP. Methods: Patients with AGC refractory to the first‑line FP regimen were randomized 1:1 to either CPT-11 (150 mg/m2, q2w) or wPTX (80 mg/m2, days 1, 8, 15, q4w). The primary endpoint was overall survival (OS) and secondary endpoints were progression‑free survival (PFS), overall response rate (ORR), adverse events and receiving rates of third-line CT. To demonstrate an increase in median OS from 5 months (wPTX) to 7.5 months (CPT-11) with 2-sided alpha 5% and 80% power, 220 pts were required. Results: Between Aug 2007 and Aug 2010, 223 pts were enrolled; 112 pts were randomized to CPT-11 and 111 pts to wPTX. Baseline characteristics were well balanced between arms. Median OS was 8.4 months for CPT-11 and 9.5 months for wPTX (HR 1.132; 95% CI, 0.86-1.49; p=0.38). Median PFS was 2.3 months for CPT-11 and 3.6 months for wPTX (HR 1.14; 95% CI, 0.88-1.49; p=0.33). The ORR was 13.6% (12/88) for CPT-11 and 20.9% (19/91) for wPTX (p=0.20). The most common grade 3/4 adverse events were neutropenia (39.1% for CPT-11 vs. 28.7% for wPTX), anemia (30.0% vs. 21.3%), anorexia (17.3% vs. 7.4%) and fatigue (12.7% vs. 6.5%). Four (4%) CPT-11 and three (3%) wPTX recipients died within 30 days after the last administration. Subsequent CT was performed in 80 pts (71%) for CPT-11 and 97 pts (89%) for wPTX. Seventy-five pts (67%) in the CPT-11 group and 87 pts (80%) in the wPTX group received the crossover CT. Conclusions: The WJOG4007 trial, the first phase III study comparing second-line CT regimens for AGC, did not demonstrate the superiority of CPT-11 over wPTX. Thus, wPTX can be adopted as a control arm of future phase III trials of second-line CT for AGC.

Final results of study 20050181: A randomized phase III study of FOLFIRI with our without panitumumab (pmab) for the second‑line treatment (tx) of metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3535-3535 ◽  
Author(s):  
Alberto F. Sobrero ◽  
Marc Peeters ◽  
Timothy Jay Price ◽  
Yevhen Hotko ◽  
Andres Cervantes-Ruiperez ◽  
...  
Keyword(s):  
Descriptive Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Second Line ◽  
Primary Analysis ◽  
Primary Endpoints ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
Event Rates

3535 Background: The primary analysis of study 20050181 showed that in patients (pts) with wild-type (WT) KRAS mCRC, pmab plus FOLFIRI given as second-line therapy significantly improved progression-free survival (PFS) vs FOLFIRI alone. Here, we report on a prespecified descriptive analysis planned for 30 months (mos) after the last pt was enrolled. Methods: Pts with mCRC, ECOG 0-2, who had one prior fluoropyrimidine-based chemotherapy regimen were randomized 1:1 to pmab 6.0 mg/kg Q2W+FOLFIRI (Arm 1) vs FOLFIRI (Arm 2). Co-primary endpoints were OS and PFS (central assessment). Secondary endpoints included objective response rate (ORR) and safety. Tumor KRAS status was determined by a blinded central lab. Results: 1186 pts were randomised and received tx: 591 in Arm 1, 595 In Arm 2. 1083 pts (91%) had KRAS results. Adverse event rates were consistent with the primary analysis. Results are shown below. Conclusions: In pts with WT KRAS mCRC receiving pmab+FOLFIRI vs FOLFIRI, PFS and ORR were significantly improved, and there was a trend toward improved OS. Post-progression anti-EGFR tx may have attenuated any significant difference in OS between tx arms. In pts with MT KRAS mCRC, no difference in efficacy was observed between tx arms. KRAS testing is critical to select appropriate pts for tx with pmab. [Table: see text]

Evofosfamide (TH-302) in combination with gemcitabine in previously untreated patients with metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma: Primary analysis of the randomized, double-blind phase III MAESTRO study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 193-193 ◽  
Author(s):  
Eric Van Cutsem ◽  
Heinz-Josef Lenz ◽  
Junji Furuse ◽  
Josep Tabernero ◽  
Volker Heinemann ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Significant Prognostic Factor ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Double Blind

193 Background: Pancreatic ductal adenocarcinoma (PDAC) is invariably diagnosed at an advanced stage and has poor clinical outcome. Hypoxia is a significant prognostic factor in PDAC progression and is associated with poor prognosis. Evofosfamide (Evo, previously known as TH-302) is a hypoxia-activated prodrug of bromo-isophosphoramide mustard (Br-IPM) that is preferentially activated under hypoxic conditions. The addition of Evo to gemcitabine (Gem) significantly improved progression-free survival (PFS) in a randomized phase II trial in advanced PDAC (NCT01144455). Methods: MAESTRO is an international, randomized, double-blind, placebo-controlled phase III trial of Evo/Gem vs Placebo/Gem in patients (pts) with measurable, locally advanced unresectable or metastatic PDAC (NCT01746979). Evo and Gem were administered intravenously at a dose of 340 mg/m2 and 1,000 mg/m2, respectively, on days 1, 8, and 15 of a 28-day cycle. Treatment continued until disease progression. Key eligibility criteria included ECOG PS 0/1 and no neoadjuvant or adjuvant chemotherapy <6 months prior to entry. The primary endpoint was overall survival (OS) with the study designed to detect a HR of 0.75 with 90% power. Secondary endpoints included PFS and objective response rate (ORR), employing a hierarchical testing procedure with a 2-sided α=0.05 at each level. Results: A total of 693 pts were randomized to treatment with Evo/Gem (n=xxx) or Placebo/Gem (n=yyy). Baseline pt characteristics were similar between treatment arms. The OS HR was X.XX (95% CI: Y.YY, Z.ZZ; p=A.AAA). Median OS was AA.A months (m) for Evo/Gem vs BB.B m for Placebo/Gem. Median PFS was C.C m and D.D m, respectively (HR E.EE [95% CI: F.FF, G.GG; p = H.HHH). ORR was JJ.J% with Evo/Gem vs KK.K% with Placebo/Gem (p = L.LLL). Grade ≥3 adverse events (AEs) occurring in >5% of pts in treated with Evo/Gem were: TBC. Conclusions: The data from the MAESTRO trial will make an important contribution to our understanding of PDAC treatment. Clinical trial information: NCT01746979.

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