Outcomes by hypomagnesemia (hypomag) in the randomized phase III ASPECCT trial of patients (pts) with chemofractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 507-507
Author(s):  
Marc Peeters ◽  
Tae Won Kim ◽  
Jin Li ◽  
Stefano Cascinu ◽  
Paul Ruff ◽  
...  
Keyword(s):  
Ad Hoc ◽  
Final Analysis ◽  
Phase Iii ◽  
Exon 2 ◽  
Trial Analysis ◽  
Grade 3 ◽  
Dose Modifications ◽  
To Receive ◽  
Kras Exon ◽  
Clinical Trial Information

507 Background: ASPECCT demonstrated that panitumumab (pmab) was noninferior to cetuximab (cmab) for overall survival (OS). Ad hoc analyses from ASPECCT suggested that hypomag was associated with better outcomes for pmab and cmab (Price 2015). However, results from the phase 3 NCIC CTG/AGITG CO.17 trial indicated hypomag at day 28 was associated with worse outcomes for cmab (Vickers 2013). Methods: Patients (pts) with chemorefractory WT KRASexon 2 mCRC were randomized 1:1 to receive pmab or cmab. Ad hoc analyses by hypomag were performed from the final analysis of ASPECCT at week 5, consistent with the NCIC CTG/AGITG CO.17 trial analysis (Vickers, 2013). Results: 999 pts were treated: 496 received pmab and 503 received cmab. Any grade hypomag was 29.0% and grade ≥3 was 7.3% in the pmab arm vs 19.3% and 2.8% in the cmab arm, respectively. In the pmab arm, 1.2% of pts discontinued treatment and 5% of pts had dose modifications due to hypomag vs 0.4% and 3% in the cmab arm, respectively. Efficacy results by hypomag are shown (Table). Conclusions: In ASPECCT, rates of hypomag were higher in the pmab vs the cmab arm. Pts who developed any grade hypomag with pmab or cmab had longer median OS compared with those pts who did not. Consistent with previous analyses, development of hypomag at week 5 was associated with worse median OS for cmab. Clinical trial information: NCT01001377. [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]

Final analysis of KEYNOTE-189: Pemetrexed-platinum chemotherapy (chemo) with or without pembrolizumab (pembro) in patients (pts) with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9582-9582
Author(s):  
Delvys Rodriguez-Abreu ◽  
Steven Francis Powell ◽  
Maximilian Hochmair ◽  
Shirish M. Gadgeel ◽  
Emilio Esteban ◽  
...  
Keyword(s):  
Final Analysis ◽  
Phase Iii ◽  
First Line ◽  
Primary Endpoints ◽  
Improved Outcomes ◽  
Grade 3 ◽  
Platinum Chemotherapy ◽  
To Receive ◽  
Clinical Trial Information ◽  
Nonsquamous Nsclc

9582 Background: The phase III KEYNOTE-189 study (NCT02578680), showed significant improvements in OS and PFS with pembro + chemo vs placebo + chemo in pts with previously untreated metastatic nonsquamous NSCLC without sensitizing EGFR/ALK mutations. We report the protocol-specified final analysis of KEYNOTE-189. Methods: Pts were randomized 2:1 to receive 35 cycles of pembro 200 mg Q3W (n = 410) or placebo Q3W (n = 206) plus 4 cycles of pemetrexed (pem) and carboplatin/cisplatin followed by maintenance pem. Pts in the placebo + chemo arm could crossover to pembro upon PD. PFS and OS were primary endpoints; ORR was a secondary endpoint. PFS2 (time from randomization to objective tumor progression on next-line treatment/death), was an exploratory endpoint. Results: At data cutoff (May 20, 2019), median (range) time from randomization to data cutoff was 31.0 (26.5–38.8) mo. 17 pts in the pembro + chemo arm and 1 pt in the placebo + chemo arm were receiving initially assigned treatment; 84 pts crossed over to pembro. Median (95% CI) OS (22.0 [19.5–24.5] vs 10.6 [8.7–13.6] mo; HR 0.56 [95% CI, 0.46–0.69]) and PFS (9.0 [8.1–10.4] vs 4.9 [4.7–5.5] mo; HR 0.49 [95% CI, 0.41–0.59]) were longer with pembro + chemo vs placebo + chemo (Table). The 2-y OS rate was 45.7% vs 27.3% and the 2-y PFS rate was 22.0% vs 3.4%. ORR was 48.3% with pembro + chemo vs 19.9% with placebo + chemo. 56 pts in the pembro + chemo arm completed 35 cycles of pembro among whom ORR was 85.7% (4 CR, 44 PR, 8 SD) and median OS was not reached. 292 (72.1%) pts in the pembro + chemo arm and 135 (66.8%) pts in the placebo + chemo arm had grade 3–5 AEs. Conclusions: Pembro + chemo continued to show improved outcomes in OS, PFS, ORR and PFS2 compared with placebo + chemo, with manageable toxicity. These findings support first-line pembro + chemo in pts with previously untreated metastatic nonsquamous NSCLC. Clinical trial information: NCT02578680 . [Table: see text]

Regorafenib (REG) in progressive metastatic colorectal cancer (mCRC): Analysis of age subgroups in the phase III CORRECT trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3636-3636 ◽  
Author(s):  
Eric van Cutsem ◽  
Alberto Sobrero ◽  
Salvatore Siena ◽  
Alfredo Falcone ◽  
Marc Ychou ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
P Value ◽  
Correct Trial ◽  
Multikinase Inhibitor ◽  
Once Daily ◽  
Grade 3 ◽  
Dose Modifications ◽  
The Impact ◽  
To Receive

3636 Background: In the CORRECT phase III trial, the multikinase inhibitor REG demonstrated significant improvement in overall survival (OS) and progression-free survival vs placebo (Pla) in patients (pts) with mCRC whose disease progressed on other standard therapies. The most frequent REG-related grade ≥3 adverse events (AEs) of interest were hand–foot skin reaction (HFSR), fatigue, diarrhea, hypertension, and rash/desquamation. We explored whether the impact of REG in pts aged ≥65 years differed from that in younger patients. Methods: Pts with mCRC progressing following all other available therapies were randomized 2:1 to receive REG 160 mg once daily (n=505) or Pla (n=255) for the first 3 weeks of each 4-week cycle. The dose could be modified to manage AEs. The primary endpoint was OS. We report efficacy, safety, and dosing data from REG recipients by age. Results: The REG treatment group included 309 pts <65 years (307 evaluable for safety) and 196 pts ≥65 years (193 evaluable for safety). The OS hazard ratio (REG/Pla) was 0.72 (95% confidence interval [CI] 0.56–0.91) in pts <65 years and 0.86 (95% CI 0.61–1.19) in pts ≥65 years (interaction p-value = 0.405). Median OS was 6.7 vs 5 months for REG vs Pla in pts <65 years, and 6.0 vs 5.6 months, respectively, in pts ≥65 years. Most pts experienced drug-related AEs (<65 years: 93.8%; ≥65 years: 91.7%). The rates of grade ≥3 REG-related AEs of interest and dose modifications are shown in the Table. In pts <65 years vs ≥65 years, median (interquartile range [IQR]) duration of REG was 7.6 weeks (6.6–15.4) vs 7.1 weeks (5.1–17.2), median (IQR) daily REG dose was 160.0 mg (134.6–160.0) vs 160.0 mg (137.5–160.0), and median (IQR) proportion of planned REG dose was 83.3% (65.7–100.0) vs 78.6% (66.7–100.0), respectively. Conclusions: In the CORRECT trial, REG demonstrated an OS benefit in pts <65 years and ≥65 years. Safety and tolerability of REG appeared to be similar in both age subgroups. Clinical trial information: NCT01103323. [Table: see text]

An open label, randomized phase III trial evaluating the treatment (tx) effects of panitumumab (pmab) + best supportive care (BSC) versus BSC in chemorefractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) and in WT RAS mCRC.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 642-642 ◽  
Author(s):  
Tae Won Kim ◽  
Anneli Elme ◽  
Zvonko Kusic ◽  
Joon Oh Park ◽  
Anghel Adrian Udrea ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Open Label ◽  
Exon 2 ◽  
Ras Mutation ◽  
Secondary Endpoints ◽  
To Receive ◽  
Kras Exon

642 Background: An overall survival (OS) benefit in WT KRAS exon 2 mCRC was not seen with pmab monotherapy in study 20020408 possibly due to crossover of patients (pts) in the BSC arm. Retrospective analyses have indicated that other KRAS and NRAS mutations beyond KRAS exon 2 are predictive of anti-EGFR tx effects. Study 20100007 assesses the OS benefit of pmab in chemorefractory WT KRAS exon 2 mCRC and is the first phase 3 trial to prospectively evaluate pmab tx effects in WT RAS (exons 2, 3, and 4 of KRAS and NRAS) mCRC. Methods: Anti-EGFR naive pts were randomized 1:1 to receive pmab (6 mg/kg Q2W) + BSC or BSC. KRAS exon 2 and RAS mutation status of tumors were determined centrally. The primary endpoint was OS in WT KRAS exon 2 mCRC. Secondary endpoints were OS in WT RAS mCRC and progression-free survival (PFS), objective response rate (ORR), and safety in both WT KRAS exon 2 and WT RAS groups. Crossover was not permitted. Results: 377 pts with WT KRAS exon 2 mCRC were enrolled. RAS ascertainment rate was 86%. OS was significantly improved with pmab + BSC vs BSC in both WT KRAS exon 2 (HR=0.73, 95% CI=0.57-0.93, P=0.0096) and WT RAS (HR=0.70, 95% CI=0.53-0.93, P=0.0135) mCRC (results in table). Pts with mutant RAS mCRC did not benefit from pmab tx (OS HR=0.99, 95% CI=0.49-2.00). No new safety signals were seen. Conclusions: Pmabsignificantly improved OS in chemorefractory WT KRAS exon 2 mCRC. The tx effects in OS and PFS were more pronounced in those with WT RAS mCRC, further substantiating the importance of RAS testing at diagnosis to best inform the use of pmab to treat mCRC. Clinical trial information: NCT01412957. [Table: see text]

Analysis of KRAS/NRAS mutations in PEAK: A randomized phase II study of FOLFOX6 plus panitumumab (pmab) or bevacizumab (bev) as first-line treatment (tx) for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3631-3631 ◽  
Author(s):  
Lee Steven Schwartzberg ◽  
Fernando Rivera ◽  
Meinolf Karthaus ◽  
Gianpiero Fasola ◽  
Jean-Luc Canon ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Progression Free Survival ◽  
Primary Analysis ◽  
Exon 2 ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Exon 4 ◽  
Grade 3 ◽  
Kras Exon ◽  
Clinical Trial Information

3631 Background: PEAK estimated the tx effect of FOLFOX6 with pmab or bev in 1st-line WT KRAS mCRC. The PRIME study showed significantly improved progression free survival (PFS) and overall survival (OS) with pmab + FOLFOX vs FOLFOX in pts with WT RAS (KRAS/NRAS exons 2, 3, 4) mCRC in a prospective-retrospective analysis (unpublished data). Methods: This prospective-retrospective analysis of PEAK was designed to assess the effect of pmab + FOLFOX6 or bev + FOLFOX6 on PFS (primary endpoint) and OS in WT RAS (KRAS/NRAS exons 2, 3, 4) mCRC. Pts were required to have WT KRAS exon 2 tumors. Bidirectional Sanger sequencing and Transgenomic SURVEYOR/WAVE analysis were independently conducted to detect mutations in KRAS exon 3 (codons 59/61), exon 4 (codons 117/146); NRAS exon 2 (codons 12/13), exon 3 (codons 59/61), exon 4 (codons 117/146); BRAF exon 15 (codon 600) in banked specimens. Results: 285 WT KRAS (exon 2) mCRC patients (pts) were randomized, 278 received tx. The current RAS ascertainment rate is 75%. Tx HRs (pmab:bev) for pts with WT RAS were 0.63 (95% CI, 0.43-0.94; p = 0.02) for PFS and 0.55 (95% CI, 0.30-1.01; p = 0.06) for OS (Table). The incidence of worst grade 3-5 adverse events was consistent with the primary analysis. Updated OS and BRAF results will be presented. Conclusions: In this 1st-line estimation study in WT RAS mCRC, PFS and OS HR favored pmab + FOLFOX6 relative to bev + FOLFOX6, suggesting that activating RAS mutations appear to be predictive for pmab tx effect. The safety profile for both arms was consistent with previously reported studies. Clinical trial information: NCT00819780. [Table: see text]

Efficacy of panitumumab (pmab) vs. cetuximab (cmab) in patients (pts) with wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) treated with prior bevacizumab (bev): Results from ASPECCT.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 519-519 ◽  
Author(s):  
Marc Peeters ◽  
Tae Won Kim ◽  
Jin Li ◽  
Stefano Cascinu ◽  
Paul Ruff ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Ecog Performance Status ◽  
Exon 2 ◽  
Hazard Ratios ◽  
Metastatic Sites ◽  
To Receive ◽  
Kras Exon

519 Background: The phase 3 ASPECCT trial of pts with chemorefractory WT KRAS exon 2 mCRC demonstrated that pmab was noninferior to cmab for overall survival (OS). A previous subgroup analysis of hazard ratios (HRs) suggested that pts who had received prior bev (any line, at any point before study start) in the pmab arm may have had better outcomes vs pts in the cmab arm (Price, 2014). Methods: Pts were randomized 1:1 to receive pmab or cmab. The subset of pts who had received prior bev were analyzed based on the final analysis of ASPECCT. Results: 999 pts were randomized and treated: 499 pmab and 500 cmab. The prior bev subset included 126 pts in the pmab arm (25%) and 132 pts in the cmab arm (26%). Pts in the pmab arm had longer median OS and progression-free survival (PFS) and higher objective response rates (ORR) compared with pts in the cmab arm. Results are shown (table). After adjustment for baseline covariates including ECOG performance status, number of metastatic sites, and baseline LDH, OS HR was 0.65 (95%CI=0.49-0.85) with pmab vs cmab in pts who had received prior bev. Pts in the pmab and cmab arms who did not receive prior bev had similar OS, PFS, and ORR. Post-progression antitumor therapy was similar between the pmab (47%) and cmab arms (52%) in pts who received prior bev. Conclusions: In ASPECCT, pts with WT KRASexon 2 mCRC who received prior bev-containing regimens may have derived greater benefit with pmab versus cmab monotherapy. Clinical trial information: NCT01001377. [Table: see text]

Randomized Comparison of Standard Induction with Daunorubicin (DNR) for 3 Days vs Idarubicin (IDA) for 3 or 4 Days in AML pts Aged 50 to 70 and of Maintenance with Interleukin 2. Final Analysis of the ALFA 9801 Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 162-162 ◽  
Author(s):  
Cecile Pautas ◽  
Xavier Thomas ◽  
Fatiha Merabet ◽  
Emmanuel Raffoux ◽  
Jean Henri Bourhis ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Final Analysis ◽  
Risk Groups ◽  
Salvage Chemotherapy ◽  
Phase Iii ◽  
High Dose ◽  
Duration Of Hospitalization ◽  
High Doses ◽  
Grade 3 ◽  
To Receive

Abstract Background: For many years the ALFA Group has used high dose DNR, i.e 80 mg/m2/day for 3d as part of the induction regimen for untreated adult AML pts. As the equivalence of DNR and Ida is not known we conducted a phase III study to compare high dose DNR to Ida. We also tested the effect of IL2 for maintenance. Methods: Newly diagnosed AML, aged 50 to 70 years, were randomized to receive AraC 200 mg/m2/day IV x 7 d with either DNR: 80 mg/m2/d x 3 d (arm 1) or Ida: 12 mg/m2/d x 3 d (arm 2) or x 4 d (arm 3). Pts who failed could receive a salvage course with Mitoxantrone x 2 d and AraC1g/m2 12 hrs x 4d. Response was assessed after induction+/− salvage chemotherapy. CR pts received 2 consolidation courses according to the induction arm with DNR: 80 mg/m2 or Ida:12 mg/m2 for 1 day (first course) or 2 days (2nd course) and AraC:1g/m2/12 hrs x 4 days. Pts in CCR after the two consolidation courses were randomized to receive or not a maintenance immunotherapy with IL2: 5.106/m2 for 5 days monthly for12 months. Results: From 2001 to 2006, 468 pts were included (median age: 60 years). The 3 treatment arms were well matched for pretreatment characteristics. CR was achieved in 360/468 pts (77%): 109 (70%) pts arm 1, 129 (83%) arm 2, 122 (78%) arm 3 (p=0.02).70 pts, (45%) pts in the DNR arm reached CR after 1 course vs 97 (62%) and 90 (57%) in Ida arms (p= 0.006). Pts in Ida arms experienced more grade 3 or 4 mucositis (p=0.004) but no differences were observed between the 3 arms for duration of hospitalization, time to PMN or plts recovery, incidence of grade 3 or 4 infectious episodes and treatment related mortality. 3 year cumulative incidence of relapse was 69%, 63%, 62% resp in arms 1,2,3 (p=NS). 3 year EFS was 19%, 30%, 26% resp (p=0.06 for arm 1 vs arms 2 and 3). 3 year OS was 31%, 40% 41% resp in arms 1,2,3 (p=NS). Age (&lt; or &gt;60 years), sex, initial WBC counts, initial LDH (nl or &gt;nl), DNR or Ida arms, need for a salvage course were not predictive for relapse, while 2yCIR was 43%, 64%, 77% among respectively fav, intermediate and unfav cytogenetic risk groups resp (p=0.0046). Of the 219 pts alive in CR after consolidations, 161 (73%) were randomized for maintenance. Only 22 of the 77 pts randomized for IL2 completed the 1 year treatment. 32 and 23 pts stopped IL2 resp because of relapse or intolerance. There were no differences in relapse or OS in both maintenance arms. Conclusion: Ida treatment even when compared to high doses of DNR yields higher CR rate and more CR after one course. This effect translated in slightly better EFS but not better CIR or OS. IL2 maintenance treatment at least as scheduled in this trial was difficult to apply and showed no impact on disease course.

Overall survival (OS) analysis from PRIME: Randomized phase III study of panitumumab (pmab) with FOLFOX4 for first-line metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3620-3620 ◽  
Author(s):  
Jean-Yves Douillard ◽  
Salvatore Siena ◽  
Josep Tabernero ◽  
Ronald L. Burkes ◽  
Mario Edmundo Barugel ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
First Line ◽  
Primary Analysis ◽  
Ecog Performance Status ◽  
Exon 2 ◽  
Kras Exon

3620 Background: The primary and final analyses of PRIME demonstrated that pmab + FOLFOX4 significantly improved progression-free survival (PFS) vs FOLFOX4 alone for first-line treatment of patients (pts) with wild-type (WT) KRAS exon 2 mCRC. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg every 2 weeks + FOLFOX4 or FOLFOX4 alone and had no prior chemotherapy for mCRC, ECOG performance status ≤ 2, and tumor tissue for biomarker testing. The primary endpoint was PFS by central assessment. Secondary endpoints included OS, objective response rate, and safety. KRAS exon 2 tumor status was determined by a blinded central lab prior to the primary analysis. This exploratory analysis of updated survival (>80% OS events) estimated the treatment effect of pmab + FOLFOX4 compared with FOLFOX4 alone on OS by KRAS exon 2 status. Previous analyses in pts with WT KRAS exon 2 tumor status reported OS with an event rate of 54% of pts in the primary analysis and 68% of pts in the final analysis. Results: 1183 pts were randomized and received treatment: 593 pts in the pmab + FOLFOX4 arm and 590 pts in the FOLFOX4 alone arm. The KRAS exon 2 ascertainment rate was 93%, consistent with the primary analysis. 535/656 pts (82%) with WT KRAS exon 2 mCRC had an OS event at the time of this analysis. Results are shown (Table). Conclusions: In this updated analysis, an improvement in OS was observed in pts with WT KRAS exon 2 mCRC treated with pmab + FOLFOX4 vs FOLFOX4 alone (p = 0.03). Median OS was reduced in pts with mutant (MT) KRAS mCRC (p = 0.16) and is consistent with previous analyses. Updated efficacy and safety results will be presented. KRAS testing is critical to select appropriate pts with mCRC for treatment with pmab. Clinical trial information: NCT00364013. [Table: see text]

Early tumor shrinkage (ETS) and depth of response (DpR) in wild-type (WT) RAS tumors from the phase III trial of panitumumab (pmab) plus best supportive care (BSC) versus BSC in chemorefractory metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3561-3561 ◽  
Author(s):  
Tae Won Kim ◽  
Anneli Elme ◽  
Joon Ho Park ◽  
Anghel Adrian Udrea ◽  
Nebojsa S. Manojlovic ◽  
...  
Keyword(s):  
Final Analysis ◽  
Best Supportive Care ◽  
Tumor Burden ◽  
Phase Iii ◽  
Tumor Shrinkage ◽  
Exon 2 ◽  
Depth Of Response ◽  
Early Tumor ◽  
A Prospective Study ◽  
Kras Exon

3561 Background: Activating RAS mutation is a negative predictor of anti-EGFR therapy. In the final analysis of 20100007, the first phase 3 study to prospectively evaluate efficacy and safety of WT RAS ( KRAS and NRAS exons 2, 3, 4 ) mCRC, pmab + BSC continued to show improved survival (OS and PFS) and ORR. Recent data suggest that tumor burden reduction and ETS may contribute to improved OS. Previous studies have shown that pmab plus chemotherapy results in ETS, which correlates with OS benefit (Douillard et al, EJC, 2015; Rivera et al, JCO, 2015; Mansmann et al, JCO 2013). Here we report analyses of ETS and DpR and the effect on OS in patients (pts) with WT RAS mCRC treated with pmab monotherapy in the ‘0007 trial. Methods: Anti-EGFR naïve pts with WT KRAS exon 2 mCRC were randomized 1:1 to pmab + BSC or BSC. Pt tumors were further evaluated for RAS status, and DpR (percent tumor shrinkage at nadir or progression) and ETS (≥/< 0% or ≥/< 20% by week 8) were analyzed in WT RAS pts. OS and PFS were compared for each ETS group. Results: Of 377 pts with WT KRAS exon 2 mCRC, 270 were WT RAS (142 pmab + BSC, 128 BSC alone). In the pmab + BSC arm, 69.5% and 38.2% of pts had ≥0% and ≥20% ETS, respectively, and median (Q1, Q3) DpR was 16.9% (0%, 37.5%). OS was improved in pts with higher ETS (≥0% or ≥20%) compared with lower ETS (<0% or <20%; Table). Conclusions: In this post-hoc analysis, pmab monotherapy provided any ETS benefit (≥0%) in 69.5% of WT RAS mCRC pts, and ETS was associated with improved PFS and OS. Pmab should be considered both in combination and as monotherapy for its significant impact on OS and also for its ability for substantial ETS in pts with WT RAS mCRC. Validation is necessary to investigate the value and cutoff of ETS in a prospective study. Clinical trial information: NCT01412957. [Table: see text]

TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5062-5062
Author(s):  
Sumanta K. Pal ◽  
Bernard Escudier ◽  
Michael B. Atkins ◽  
Thomas E. Hutson ◽  
Camillo Porta ◽  
...  
Keyword(s):  
Final Analysis ◽  
Phase Iii ◽  
Risk Category ◽  
Open Label ◽  
Cancer History ◽  
Open Label Study ◽  
Prior Therapy ◽  
Grade 3 ◽  
Vegfr Inhibitor ◽  
Clinical Trial Information

5062 Background: Tivozanib (T) is a potent and highly selective VEGFR inhibitor. TIVO-3 is a phase 3 study designed to compare the efficacy and safety of T with those of sorafenib (S) as 3rd and 4th line therapy in patients with metastatic RCC. Methods: Subjects with RCC who failed 2 or 3 prior systemic regimens, one of which included a VEGFR TKI other than S or T, were stratified by IMDC risk category and type of prior therapy (two TKIs; TKI plus checkpoint inhibitor (CPI); TKI plus other) then randomized in a 1:1 ratio to T or S. Results: The 2 arms were well balanced for demographics and prior cancer history. 60% of subjects had 2 prior lines of therapy and 40% had 3 prior lines. 26% had prior treatment with a CPI. Patients treated with T demonstrated PFS superiority compared to S, 5.6 (95% CI 7.3 - 5.3) v. 3.9 mos (95% CI 5.6 – 3.7; HR 0.73; p=0.02). ORR was 18% for T compared to 8% for S (p=0.02). 44% of T treated subjects experienced a grade 3 treatment-related adverse event compared to 55% for S. The predefined, interim analysis for OS performed two years after enrollment was closed had a HR of 0.99 based on 227 events. The final analysis will be presented based on an estimate of 263 events. Conclusions: T is superior to S as measured by PFS; 2-year PFS, and ORR in this heavily-treated/relapsed or refractory RCC population and is better tolerated than S. Final OS data will be updated prior to presentation. Clinical trial information: 02627963 .

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