Outcomes based on age in the phase 3 METEOR trial of cabozantinib (cabo) versus everolimus (eve) in patients with advanced renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 517-517 ◽  
Author(s):  
Frede Donskov ◽  
Robert J. Motzer ◽  
Eric Voog ◽  
Elizabeth J. Hovey ◽  
Carsten Grüllich ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Target Lesion ◽  
Free Survival ◽  
Mri Scans ◽  
Lesion Regression ◽  
The Impact ◽  
To Receive

517 Background: In the METEOR study (NCT01865747), cabo demonstrated improved progression-free survival (median 7.4 vs. 3.8 mo; HR 0.58, 95% CI 0.45–0.74; p<0.0001), OS (median 21.4 vs. 16.5 mo; HR 0.66, 95% CI 0.53-0.83, p=0.0003), and objective response rate (17% vs. 3%; p<0.0001) compared with eve in patients (pts) with advanced RCC who had received prior VEGFR TKI therapy (Choueiri NEJM 2015, Lancet Oncol 2016). Here we evaluate the impact of changes in target lesion size from baseline on OS. Methods: 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd). Stratification factors were MSKCC risk group and number of prior VEGFR TKIs. Target lesion size was assessed per independent radiology review by CT/MRI scans at baseline, every 8 weeks for the first 12 months, and every 12 weeks thereafter. Three subgroups were defined by best change in target lesion size from baseline: decrease ≥30%, decrease <30%, and any increase. Results: The rate of target lesion regression was higher in the cabo arm (75%) compared with the eve arm (48%). A higher fraction of pts had a decrease ≥30% in target lesion size in the cabo arm, while a higher fraction of pts had an increase in target lesion size in the eve arm (Table). Medians for OS with cabo were not estimable (NE) (95% CI, NE‒NE), 20.8 mo (95% CI, 18.1‒NE), and 11.1 mo (95% CI, 7.6‒15.2) for the ≥30% decrease, <30% decrease, and any increase subgroups, respectively. Medians for OS with eve were NE (95% CI, 19.3‒NE), 18.0 mo (95% CI, 15.9‒20.4), and 14.0 mo (95% CI, 10.5‒16.3) for the ≥30% decrease, <30% decrease, and any increase subgroups, respectively. Median duration of follow-up for OS was 18.7 mo (IQR 16.1–21.1) for cabo and 18.8 mo (16.0–21.2) for eve. A higher proportion of pts received subsequent anticancer therapy in the any increase subgroup compared with the other subgroups. Conclusions: Cabo demonstrated a higher rate of tumor target lesion regression than eve, and greater target lesion regression was associated with improved OS in pts with advanced RCC. Clinical trial information: NCT01865747.

Analysis of overall survival (OS) based on tumor target lesion change in the phase 3 METEOR trial of cabozantinib (cabo) versus everolimus (eve) in advanced renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 522-522
Author(s):  
Sumanta K. Pal ◽  
Robert J. Motzer ◽  
Mayer N. Fishman ◽  
Raymond S. McDermott ◽  
Jose Passos-Coelho ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Target Lesion ◽  
Tumor Target ◽  
Mri Scans ◽  
Lesion Regression ◽  
The Impact ◽  
To Receive

522 Background: In the METEOR study (NCT01865747), cabo demonstrated improved progression-free survival (median 7.4 vs. 3.8 mo; HR 0.58, 95% CI 0.45–0.74; p<0.0001), OS (median 21.4 vs. 16.5 mo; HR 0.66, 95% CI 0.53-0.83, p=0.0003), and objective response rate (17% vs. 3%; p<0.0001) compared with eve in patients (pts) with advanced RCC who had received prior VEGFR TKI therapy (Choueiri NEJM 2015, Lancet Oncol 2016). Here we evaluate the impact of changes in target lesion size from baseline on OS. Methods: 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd). Stratification factors were MSKCC risk group and number of prior VEGFR TKIs. Target lesion size was assessed per independent radiology review by CT/MRI scans at baseline, every 8 weeks for the first 12 months, and every 12 weeks thereafter. Three subgroups were defined by best change in target lesion size from baseline: decrease ≥30%, decrease <30%, and any increase. Results: The rate of target lesion regression was higher in the cabo arm (75%) compared with the eve arm (48%). A higher fraction of pts had a decrease ≥30% in target lesion size in the cabo arm, while a higher fraction of pts had an increase in target lesion size in the eve arm (Table). Medians for OS with cabo were not estimable (NE) (95% CI, NE‒NE), 20.8 mo (95% CI, 18.1‒NE), and 11.1 mo (95% CI, 7.6‒15.2) for the ≥30% decrease, <30% decrease, and any increase subgroups, respectively. Medians for OS with eve were NE (95% CI, 19.3‒NE), 18.0 mo (95% CI, 15.9‒20.4), and 14.0 mo (95% CI, 10.5‒16.3) for the ≥30% decrease, <30% decrease, and any increase subgroups, respectively. Median duration of follow-up for OS was 18.7 mo (IQR 16.1–21.1) for cabo and 18.8 mo (16.0–21.2) for eve. A higher proportion of pts received subsequent anticancer therapy in the any increase subgroup compared with the other subgroups. Conclusions: Cabo demonstrated a higher rate of tumor target lesion regression than eve, and greater target lesion regression was associated with improved OS in pts with advanced RCC. Clinical trial information: NCT01865747. [Table: see text]

Efficacy of avelumab plus axitinib (A + Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 302-302
Author(s):  
Yoshihiko Tomita ◽  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Risk Factors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Risk Groups ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
To Receive

302 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated progression-free survival (PFS) and objective response rate (ORR) benefit across IMDC risk groups (favorable, intermediate, and poor) vs S in patients with previously untreated aRCC. Here we report efficacy of A + Ax vs S by number of IMDC risk factors (0, 1, 2, 3, and 4-6) and target tumor sites (1, 2, 3, and ≥4) at baseline from the second interim analysis of overall survival (OS). Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1) and OS were assessed. Results: At data cut-off (Jan 2019), median (m) follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by number of IMDC risk factors and target tumor sites at baseline. A + Ax generally demonstrated efficacy benefit vs S across subgroups. Conclusions: With extended follow-up, A + Ax generally demonstrated efficacy benefit vs S across the number of IMDC risk factors and tumor sites at baseline in aRCC. OS was still immature; follow-up for the final analysis is ongoing. Clinical trial information: NCT02684006 . [Table: see text]

Post-cross-over activity of regorafenib (RE) in soft tissue sarcoma: Analysis from the REGOSARC trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11052-11052
Author(s):  
Nuria Kotecki ◽  
Thomas Brodowicz ◽  
Axel Le Cesne ◽  
Marie-Cecile Le Deley ◽  
Jennifer Wallet ◽  
...  
Keyword(s):  
Active Drug ◽  
Progression Free Survival ◽  
Growth Modulation ◽  
Cox Models ◽  
Free Survival ◽  
Phase 2 Trial ◽  
The Impact ◽  
To Receive ◽  
Clinical Trial Information

11052 Background: Based on the placebo (PBO) controlled phase 2 trial (Mir, Lancet Oncol 2016), RE has shown to be an active drug in patients (pts) with leiomyosarcoma (LMS), synovial sarcoma (SS) and other non-adipocytic sarcoma (OTH), but not in liposarcoma. Pts initially allocated to PBO were allowed to cross-over to RE after progression. We here report the activity of RE after cross-over. Methods: From July 2013 to Dec 2014, 138 pts were enrolled in the non-adipocytic sarcoma cohorts (LMS, SS & OTH). After update in Dec 2016, median follow-up was 32 mo (vs 17 mo in the initial publication). Benefit of RE vs PBO in terms of progression-free survival (PFS) and overall survival (OS) from randomization was estimated by hazard ratio (HR) in Cox models. In the PBO arm, intra-patient benefit of RE after cross-over was evaluated by the growth modulation index (GMI), where PFS1=PFS with PBO before cross-over, and PFS2=PFS with RE after cross-over. The impact of timing of RE allocation (delayed after cross-over, vs early at study entry) was evaluated by comparing PFS after cross-over in PBO arm to PFS after randomization in RE arm. Results: As detailed in the table, major PFS benefit of RE vs PBO allocated by randomization was confirmed with long follow-up (HR=0.50 [95%CI 0.35-0.71] p<.0001). However, this translates into a smaller and non-significant OS benefit (HR=0.78 [0.54-1.12] p=.18). This finding may partially be explained by the fact that 55 of the 68 pts who progressed in the PBO arm (81%) could receive RE after progression and benefit from RE: 56% of them had a GMI greater than 1.3. Delayed start of RE was associated with a non-significantly shorter PFS compared to earlier treatment (HR=1.21, [0.84-1.73] p=.30). Conclusions: Efficacy of RE vs PBO is confirmed with longer follow-up in non-adipocytic sarcoma. PFS of pts receiving RE after cross-over is not significantly shorter than that of pts initially randomized to receive RE. Clinical trial information: NCT01900743. [Table: see text]

Analysis of overall survival (OS) based on early tumor shrinkage in the phase III METEOR study of cabozantinib (cabo) versus everolimus (eve) in advanced renal cell carcinoma (RCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 550-550 ◽  
Author(s):  
Ignacio Duran ◽  
Pablo Maroto ◽  
Cristina Suárez ◽  
Daniel E. Castellano ◽  
Xavier Garcia del Muro ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Target Lesion ◽  
Phase Iii ◽  
Early Tumor Shrinkage ◽  
Tumour Shrinkage ◽  
Mri Scans ◽  
Previously Treated ◽  
Early Tumor

550 Background: In the phase 3 METEOR study (NCT01865747), cabo improved OS (median 21.4 vs 16.5 mo; HR, 0.66; 95% CI, 0.53–0.83), progression-free survival and objective response rate compared with eve in patients (pts) with previously treated advanced RCC (Choueiri 2016). Retrospective studies have shown that early tumour shrinkage (eTS), based on target lesion reduction from baseline to first post-baseline scan, has predictive value for targeted therapies in RCC (Grunwald 2015; Grunwald 2016); here we evaluate its impact on OS in METEOR. Methods: In total, 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd), stratified by MSKCC risk group and number of prior VEGFR TKIs. Target lesion size was assessed by independent radiology review using CT/MRI scans at baseline, every 8 wk for the first 12 mo and every 12 wk thereafter. Median OS was estimated for pts with ≥30% eTS, any eTS or no eTS at first post-baseline scan (week 8); data cutoff, 2 October 2016 (Motzer 2018). Results: Median follow-up was 28 mo (IQR 25, 30). Median (range) time to objective response was 1.91 (1.6, 11.0) mo with cabo and 2.14 (1.9, 9.2) mo with eve, and corresponded to the time to the first post-baseline scan. A greater proportion of pts had ≥30% eTS with cabo (20%) than with eve (5%) and the rate of any eTS was higher in the cabo arm (73%) than with eve (47%; Table). Median OS with cabo vs eve for pts with ≥30% eTS was not reached (NR; 95% CI, 23.7–NR) vs 10.2 mo (95% CI, 3.9–NE), respectively (stratified HR, 0.45; 95% CI, 0.21–0.95; p<0.05). Median OS with cabo vs eve for pts with any eTS was 23.7 (95% CI, 21.7–27.7) vs 17.3 mo (95% CI, 15.4–20.8), respectively; (stratified HR, 0.62; 95% CI, 0.48–0.80; p<0.05). OS was similar for cabo and eve for pts with no eTS. Conclusions: Cabo demonstrated a higher rate and greater magnitude of eTS at first post-baseline scan compared with eve, and eTS was associated with prolonged OS in pts treated with cabo. Clinical trial information: NCT01865747. [Table: see text]

Prevalence and outcomes of patients (pts) with EGFR S492R ectodomain mutations in ASPECCT: Panitumumab (pmab) vs. cetuximab (cmab) in pts with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 740-740 ◽  
Author(s):  
Timothy Jay Price ◽  
Kathryn Newhall ◽  
Marc Peeters ◽  
Tae Won Kim ◽  
Jin Li ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Wild Type ◽  
Exon 2 ◽  
Free Survival ◽  
Droplet Pcr ◽  
Secondary Endpoints ◽  
To Receive ◽  
Clinical Trial Information

740 Background: Mutations resistant to anti-EGFR treatment (tx), beyond those in RAS, have been reported and include EGFR S492R. We report results for pts with EGFR S492R mutations in the phase 3 ASPECCT trial. Methods: Pts were randomized 1:1 to receive pmab or cmab. Crossover was not allowed. The primary endpoint was non-inferiority of overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. EGFR S492R was evaluated by digital droplet PCR in plasma samples collected pre-tx and post-tx (safety follow-up 4 wks after the last dose). Outcomes were analyzed by EGFR S492 status. Results: Of 999 pts randomized and treated, post-tx samples were available for EGFR S492 assessment from 53% of pts (261/496) in the pmab arm and 57% of pts (285/503) in the cmab arm. EGFR S492R was detected in 1% of pts in the pmab arm and 16% of pts in the cmab arm in post-tx samples. EGFR S492R was not detected in pre-tx samples. Results are shown (table). Conclusions: In a retrospective analysis of pts with available samples from ASPECCT, 16% of pts in the cmab arm and 1% of pts in the pmab developed EGFR S492R mutations. Pts with EGFR S492R in the cmab arm had longer tx duration before progressive disease (PD) and appeared to have worse OS vs pts with wild-type S492 in the cmab arm. Clinical trial information: NCT01001377. [Table: see text]

Clinical outcomes of sunitinib (Su) for patients (pts) with desmoid tumors (DT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11052-11052
Author(s):  
Salvatora tindara Miano ◽  
Guido Francini ◽  
Serenella Civitelli ◽  
Roberto Petrioli ◽  
Edoardo Francini
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Radiological Progression ◽  
Once Daily ◽  
Free Survival ◽  
First Line Therapy ◽  
Secondary Endpoints ◽  
To Receive

11052 Background: The incidence of DT is steadily increasing in pts affected by familial adenomatous polyposis (FAP) and represents the first cause of death for pts who underwent preventive proctocolectomy. Currently, there is no standard therapy for DT and Tamoxifen (20 mg once daily) + Meloxicam (15 mg once daily) (TM) is the most commonly used regimen in clinical routine. We sought to evaluate the efficacy of Su, the most active PDGFR TKI, as first-line therapy for pts with DT. Methods: In this phase II IRB approved prospective study, pts with progressive, symptomatic, or recurrent DT were randomized to receive either Su (52 mg once daily) or TM. The primary end point was progression-free survival, defined as time from treatment start to clinical or radiological progression, whichever came first, at 2 years (2yr-PFS). Secondary endpoints were rates of objective response (OR), evaluated per RECIST criteria version 1.1, time to OR (ttOR), and toxicity. Adverse events (AE) were assessed per NCI-CTCAE version 4.02. Results: Of the 32 pts enrolled, 22 received Su and 10 TM. In both groups, median age at diagnosis was 43.5 years No OR was observed in the TM group. In the Su group, 17 pts had a partial response and 5 stable disease and the ORR was 75% (95% CI, 50 to 100). At a median follow-up of 27 months, the 2yr-PFS was 81% (95% CI, 69-96) and 36% (95% CI, 22-57) in the Su cohort and TM cohort, respectively (HR = 0.13; 95% CI, 0.05- 0.31; P<0.001). The median ttOR among pts who had an OR was 24 months. In the TM group, no toxicity was observed. The most frequently reported AE in the Su group were grade 1 or 2 hypothyroidism (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). (HR: 0.260; p = 0.0035). All AE responded to dose reduction (37.5 mg). Conclusions: In a cohort of pts with progressive, recurrent, or symptomatic DT, Su seems to be well tolerated and improve 2yr-PFS and OR rate compared with TM therapy. Further prospective studies with larger samples are needed to verify these results.

Subgroup analysis from JAVELIN Renal 101: Outcomes for avelumab plus axitinib (A + Ax) versus sunitinib (S) in advanced renal cell carcinoma (aRCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 544-544 ◽  
Author(s):  
Toni K. Choueiri ◽  
Robert J. Motzer ◽  
Matthew T. Campbell ◽  
Boris Y. Alekseev ◽  
Motohide Uemura ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Outcome Data ◽  
Once Daily ◽  
Free Survival ◽  
Independent Review ◽  
Secondary Endpoints ◽  
To Receive

544 Background: In the ongoing phase 3 JAVELIN Renal 101 trial, progression-free survival (PFS) was longer (median, 13.8 vs 8.4 mo; hazard ratio, 0.69; p=0.0001) and the objective response rate (ORR) was higher (51% vs 26%) with A + Ax vs S in patients with previously untreated aRCC. Here we report outcomes from an analysis of several prespecified subgroups. Methods: Patients were randomized 1:1 to receive A (10 mg/kg) IV every 2 weeks + Ax (5 mg) PO twice daily or S (50 mg) PO once daily for 4 wk (6-wk cycle). Primary and key secondary endpoints were PFS per independent review committee (IRC; RECIST v1.1) and OS in patients with PD-L1+ tumors (≥1% of immune cells) and in patients irrespective of PD-L1 expression; other secondary endpoints included OR per IRC (RECIST v1.1). Results: A total of 886 patients were randomized; 560 (63%) had PD-L1+ tumors. At data cut-off (Jun 2018), median follow-up was 12.0 vs 11.5 mo for A + Ax vs S groups. The table shows PFS and ORR by MSKCC and IMDC risk groups (F, favorable; I, intermediate; P, poor) and PD-L1 subgroup. Similar results for prognostic risk were seen in patients with PD-L1+ tumors. Outcome data (including PFS2) for additional clinical subgroups by baseline demographics and features will be presented. Clinical trial information: NCT02684006. Conclusions: A + Ax demonstrated PFS and OR benefit across all prognostic risk groups and PD-L1 subgroups vs S in aRCC.[Table: see text]

Anemia before and during concurrent chemoradiotherapy in patients with cervical carcinoma: Effect on progression-free survival

2003 ◽  
Vol 13 (5) ◽  
pp. 633-639 ◽  
Author(s):  
A. Obermair ◽  
R. Cheuk ◽  
K. Horwood ◽  
M. Neudorfer ◽  
M. Janda ◽  
...  
Keyword(s):  
Cervical Carcinoma ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Figo Stage ◽  
Tumor Stage ◽  
Free Survival ◽  
Parametrial Involvement ◽  
The Impact ◽  
Relevant Factors

To determine the impact of anemia before and during chemoradiation in patients with cervical cancer, we collected data on hemoglobin (Hb) levels before and during treatment from 60 unselected patients with cervical carcinoma. All patients had FIGO stage IB to IVA disease and were treated with concurrent chemoradiation for the aim of cure. Patients with an Hb value below or equal to the lower 25th quartile were considered anemic. Progression-free survival (PFS) was evaluated by univariate and multivariate analyses. After a median follow-up of 26.3 months, 20 patients developed disease progression. The lowest Hb during chemoradiation (nadir Hb), the stage of disease, and parametrial involvement were correlated significantly with PFS. On multivariate analysis, the nadir Hb (relative risk [RR] 0.29) and tumor stage (RR 3.4) remained the only prognostically relevant factors predicting PFS. At 60 months the PFS was 39.1% for anemic patients and 48.0% for nonanemic patients (P < 0.0002). In patients undergoing chemoradiation for cervical carcinoma, a low nadir Hb is highly predictive of shortened PFS, whereas the Hb before treatment is prognostically not significant.

scholarly journals Safety and Efficacy of Everolimus in Adult Patients with Neuroendocrine Tumors

2012 ◽  
Vol 6 ◽  
pp. CMO.S7319 ◽  
Author(s):  
Paul E. Oberstein ◽  
M. Wasif Saif
Keyword(s):  
Neuroendocrine Tumors ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Significant Advance ◽  
Low Grade ◽  
Mtor Inhibition ◽  
Free Survival ◽  
Disease Stabilization ◽  
To Receive

Neuroendocrine tumors (NETs) consist of a diverse family of tumors which are derived from the neuroendocrine system. Most NETs are well or moderately differentiated tumors with a relatively indolent growth pattern. However, these tumors can cause significant clinical disease due to release of functional products that mediate the carcinoid syndrome and other diverse sequela. They also can grow progressively and cause symptoms from local invasion or distant metastasis. NETs are optimally treated with surgery and somatosatin analogs (SSAs) to control symptoms but are relatively insensitive to systemic chemotherapy. As a result, patients with advanced unresectable NETs have a poor prognosis. In 2011, two targeted therapies, sunitinib and everolimus were approved in the subset of progressive pancreatic NETs (pNETs). Everolimus is an oral inhibitor of the growth stimulatory mTOR pathway. In Phase 2 trials in NETs and pNETs, everolimus was well tolerated and associated with some response and widespread disease stabilization. In follow-up, randomized Phase 3 trials, everolimus was compared to placebo. In the RADIANT-2 trial, everolimus and a somatostatin analog were used in patients with functional NETs and treatment was associated with an an improvement in progression-free survival (PFS). In the RADIANT-3 trial, patients with pNET were randomized to receive everolimus or placebo along with best supportive care. Everolimus was again associated with improvement in PFS compared to placebo and it has been approved by the FDA for patients with progressive pNET. Everolimus is associated with frequent low grade toxicity but is also notable for increased rates of infection as well as non-infectious pneumonitis. mTOR inhibition with everolimus represents a significant advance in the treatment of advanced neuroendocrine tumors.

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