scholarly journals Modified GRAS Score for Prognostic Classification of Adrenocortical Carcinoma: An ENSAT Multicentre Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A165-A166
Author(s):  
Yasir Elhassan ◽  
Barbara Altieri ◽  
Sarah Berhane ◽  
Deborah Cosentini ◽  
Anna Calabrese ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Progression Free Survival ◽  
Proliferation Index ◽  
Discriminative Performance ◽  
Resection Status ◽  
Secondary Endpoints ◽  
Risk Of Disease ◽  
Personalised Treatment ◽  
The Individual ◽  
Stage 1

Abstract Background: Adrenocortical carcinoma (ACC) has an aggressive but heterogeneous behaviour. ENSAT stage and Ki67 proliferation index are used to predict clinical outcome but are limited in distinguishing patients with different risk of disease progress. We aimed to validate the prognostic role of a previously proposed points-based score (mGRAS) in a large ACC cohort. Methods: We included ACC patients who underwent adrenalectomy between 2010 and 2019, had complete clinical and histopathological data, and did not participate in our previous studies (Libe et al. Ann Oncol 2015; Lippert et al. JCEM 2018). The mGRAS score was calculated as follows: age (<50yr=0; ≥50yr =1), symptoms (no=0; yes=1), ENSAT stage (1–2=0; 3=1; 4=2), resection status (R0=0; RX=1; R1=2; R2=3), and Ki67 (0–9%=0; 10–19%=1; ≥20%=2 points), generating scores from 0 to 9 and four mGRAS groups (scores 0–1, 2–3, 4–5, and 6–9). Progression-free survival (PFS) and disease-specific survival (DSS) were the primary and secondary endpoints, respectively. The discriminative performance of mGRAS was investigated using the Harrell’s C-index and Royston-Sauerbrei’s R2D statistic. Results: A total of 942 ACC patients from 14 ENSAT centres were included (38% men; median age 50yrs (interquartile range 38, 61)). The four mGRAS groups showed superior prognostic discrimination compared to the individual clinical and histological parameters for both PFS and DSS (C-index 0.71, R2D=0.30 and 0.77, R2D=0.46, respectively); ENSAT staging was the second best discriminator (C-index 0.67, R2D 0.21 and 0.72, R2D=0.35, respectively). An even better prognostic discrimination was observed using the ten mGRAS scores individually (C-index 0.73, R2D=0.30, and 0.79, R2D=0.45 for PFS and DSS, respectively). The superiority of mGRAS was confirmed when separately considering patients treated or untreated with adjuvant mitotane (n=481 vs 314). In mitotane-treated patients, the four mGRAS groups showed better performance in predicting PFS than Ki67 index (C-index 0.66, R2D 0.18 vs C-index 0.62, R2D 0.12). Conclusion: The prognostic performance of mGRAS is superior to that of ENSAT staging and Ki67. This simple score may guide personalised treatment decisions in patients with ACC, e.g. regarding the need for adjuvant therapy and frequency of monitoring.

scholarly journals S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study

2021 ◽  
Author(s):  
Yasir S Elhassan ◽  
Barbara Altieri ◽  
Sarah Berhane ◽  
Deborah Cosentini ◽  
Anna Calabrese ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Progression Free Survival ◽  
Ki67 Index ◽  
Tumour Stage ◽  
Discriminative Performance ◽  
Prognostic Performance ◽  
Prognostic Stratification ◽  
The Individual ◽  
Stage 1 ◽  
Individual Scores

Objective: Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on ENSAT tumour stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC. Design: Multicentre retrospective study on ACC patients who underwent adrenalectomy. Methods: The S-GRAS score was calculated as a sum of the following points: tumour Stage (1-2=0; 3=1; 4=2), Grade (Ki67 index 0-9%=0; 10-19%=1; ≥20%=2 points), Resection (R)-status (R0=0; RX=1; R1=2; R2=3), Age (<50yr=0; ≥50yr=1), Symptoms (no=0; yes=1), and categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell’s C-index and Royston-Sauerbrei’s R2D statistic. Results: We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index=0.73, R2D=0.30, and C-index=0.79, R2D=0.45, respectively, all P<0.01 vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n=481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5. Conclusion: The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).

Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11565-11565
Author(s):  
Scott Schuetze ◽  
Michael Rothe ◽  
Pam K. Mangat ◽  
Liz Garrett-Mayer ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Stage Design ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

11565 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of STS pts with CDK4 amplification treated with P are reported. Methods: Eligible pts had advanced STS, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDK4 amplification and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts (66% male) with STS with CDK4 amplification were enrolled from July 2016 to Nov 2019. 1 pt was not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One pt with partial response (PR) and 12 pts with SD16+ were observed for DC and objective response (OR) rates of 48% (95% CI: 31%, 62%) and 3.7% (95% CI: 0.1%, 19%), respectively, and the null DC rate of 15% was rejected (p<0.001). 9/13 pts with DC continued on treatment for >32 weeks. 14 pts had at least one grade 3-4 AE at least possibly related to P with the most common being low WBC/platelets. Other grade 3 AEs included increased alanine aminotransferase, anemia, and fatigue. Conclusions: Monotherapy P demonstrated anti-tumor activity in heavily pre-treated pts with STS with CDK4 amplification. Additional study is warranted to confirm the efficacy of P in pts with STS with CDK4 amplification. Clinical trial information: NCT02693535. [Table: see text]

scholarly journals SAT-180 Adrenocortical Carcinoma - A Tertiary Center’s Recent 5-Year Experience

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Michal Ehrenwald ◽  
Karen Michele Tordjman ◽  
Naftali Stern ◽  
Joseph Klausner ◽  
Ido Nachmany ◽  
...  
Keyword(s):  
Rare Disease ◽  
Adrenocortical Carcinoma ◽  
Poor Prognosis ◽  
Progression Free Survival ◽  
Second Primary ◽  
Study Cohort ◽  
Time To Death ◽  
Stage 4 ◽  
Stage 1

Abstract BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis. The aim of this study was to characterize patients diagnosed with ACC at a single center between 2014-2019. METHODS: We retrospectively reviewed data regarding demographics, tumor characteristics and functionality, treatment and survival. RESULTS: The study cohort included 27 subjects (56% females), followed for 27±10.6 months. The mean age at diagnosis was 49.4±9 years. Co-morbidities at presentation included hypertension (63%), diabetes mellitus (22%) and dyslipidemia (26%). 74.1% of tumors were functioning – of which 85% were cortisol-secreting and 15% androgen-secreting. Aldosterone was secreted additionally in 15%. ENSAT stage at diagnosis was stage 1 in 15%, stage 2 in 35%, stage 3 in 12% and stage 4 in 38%. Eighty-nine % of patients underwent surgery. Treatment with mitotane was initiated in 82% of patients, reaching a mean maximal dose of 3.3 ±0.4 grams/day. Chemotherapy and/or radiation were given in 37% and 22%, respectively. Several patients (14.8%) had a second primary cancer, diagnosed before ACC in 75%. Progression was observed in 48% of patients, with a progression-free survival of 8.3±6.6 months. Thirty-five % of patients died during follow up, time to death was 12.8±0.4 months. Twenty two % of patients survived over 30 months after diagnosis. KI67 above 20% or stage above 2 negatively affected survival. CONCLUSIONS: ACC remains a rare disease with a poor prognosis. However, it is a heterogeneous disease, with some patients achieving survival of over 30 months after diagnosis. Further characterization of this population may improve our understanding of the biology and treatment of this rare disease.

Cobimetinib plus vemurafenib (C+V) in patients (Pts) with colorectal cancer (CRC) with BRAF V600E mutations: Results from the TAPUR Study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 122-122 ◽  
Author(s):  
Kelsey Klute ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Pam K. Mangat ◽  
Reza Nazemzadeh ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Stage Design ◽  
Elevated Liver Enzymes ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

122 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with BRAF V600E mutation treated with C+V are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had BRAF V600E/D/K/R mutation and no MAP2K1/2, MEK1/2, NRAS mutations. Recommended dosing was C, 60 mg orally once daily for 21 days, 7 days off and V, 960 mg orally twice daily. Simon two-stage design was used to test the null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) according to RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Thirty pts enrolled from August 2016 to August 2018; 2 were not evaluable for efficacy. Demographics and outcomes are summarized in Table. All pts had BRAF V600E mutations. Eight PR and 8 SD16+ were observed for DC and OR rates of 57% (90% CI, 43% to 67%) and 29% (95% CI, 13% to 49%), respectively. Twelve pts had at least 1 grade 3 AE or SAE at least possibly related to C+V including elevated liver enzymes, decreased lymphocytes, dyspnea, diarrhea, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, upper GI hemorrhage, and vomiting. Conclusions: The combination of C+V showed anti-tumor activity in heavily pre-treated CRC pts with BRAF V600E mutations . Further study is warranted to confirm the efficacy of C+V in this population. Clinical trial information: NCT02693535. [Table: see text]

IMmotion151: A Randomized Phase III Study of Atezolizumab Plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma (mRCC)

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 578-578 ◽  
Author(s):  
Robert J. Motzer ◽  
Thomas Powles ◽  
Michael B. Atkins ◽  
Bernard Escudier ◽  
David F. McDermott ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Anti Vegf ◽  
Treatment Naïve ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Intent To Treat ◽  
The Individual ◽  
To Receive

578 Background: Atezolizumab (atezo; anti–PD-L1) + bevacizumab (bev; anti-VEGF) showed first-line (1L) anti-tumor activity with a manageable safety profile in PD-L1+ mRCC pts in a Phase II study (McDermott ASCO-GU 2017). Here we describe the first randomized Phase III trial of a PD-L1/PD-1 pathway inhibitor combined with an anti-VEGF agent in 1L mRCC. Methods: IMmotion151 (NCT02420821) enrolled treatment-naïve pts regardless of prognostic risk group randomized 1:1 to receive atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sunitinib (sun) 50 mg PO QD 4 wk on/2 wk off. Pts were stratified by PD-L1 status (< 1% vs ≥ 1% PD-L1 expression on tumor-infiltrating immune cells [IC]; SP142 IHC assay). Coprimary endpoints: progression-free survival (PFS; by investigator per RECIST v1.1) in PD-L1+ pts (≥ 1% IC) and overall survival (OS) in intent-to-treat (ITT) pts. Secondary endpoints included PFS in ITT pts, ORR and DOR. Results: Baseline characteristics were comparable between arms within PD-L1+ (40% of ITT) and ITT pts. Median survival follow-up was 15 mo. PFS HR for atezo + bev vs sun was 0.74 (95% CI 0.57, 0.96) in PD-L1+ pts and 0.83 (95% CI 0.70, 0.97) in ITT pts. OS was immature at first interim analysis. PFS benefit was consistent across analyzed subgroups, including MSKCC risk, liver metastases and sarcomatoid histology. In PD-L1+ pts, ORR was 43% and DOR was not reached for atezo + bev vs 35% and 12.9 mo for sun. 40% of atezo + bev–treated pts and 54% of sun-treated pts had treatment-related Gr 3-4 AEs; 12% and 8% of treatment-related all-Gr AEs led to discontinuation, respectively. Conclusions: The study showed longer PFS for atezo + bev vs sun in PD-L1+ pts. Improved PFS was also observed in ITT pts. Safety was consistent with that of the individual agents. These results support the use of atezo + bev as a 1L treatment option in mRCC. Clinical trial information: NCT02420821. [Table: see text]

Palbociclib (P) in patients (pts) with non-small cell lung cancer (NSCLC) with CDKN2A alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9041-9041 ◽  
Author(s):  
Eugene R Ahn ◽  
Pam K. Mangat ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Elie G. Dib ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Stage Design ◽  
Secondary Endpoints ◽  
Targeted Agent ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

9041 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of NSCLC pts with CDKN2A loss or mutation treated with P are reported. Methods: Eligible pts had advanced NSCLC, no standard treatment options, measurable disease, ECOG PS 0-2 and adequate organ function. Genomic testing was performed using commercially available tests. Pts matched to P had NSCLC with CDKN2A loss or mutation and no RB mutations. A Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) (SD16+)), an additional 18 pts are enrolled. If ≥7 of 28 pts have DC, the drug is considered worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-nine pts were enrolled from January 2017 to June 2018; 1 pt was unevaluable for response but is included in safety analyses. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off. Demographics and outcomes are summarized in Table (N = 28). One PR and 6 SD16+ were observed for a DC rate of 29% (90% CI, 15% to 37%). 10 pts had at least one grade 3 or 4 AE or SAE at least possibly related to P with the most common being cytopenias. Other grade 3-4 AEs or SAEs at least possibly related to P included fatigue, anorexia, febrile neutropenia, myocardial infarction, sepsis, vomiting, and hypophosphatemia. Conclusions: Monotherapy with P demonstrated evidence of anti-tumor activity in heavily pre-treated NSCLC pts with CDKN2A loss or mutation . Additional study is warranted to confirm the efficacy of P in pts with NSCLC with CDKN2A loss or mutation. Clinical trial information: NCT02693535. [Table: see text]

KRT-232, a first-in-class, murine double minute 2 inhibitor (MDM2i), for TP53 wild-type (p53WT) Merkel cell carcinoma (MCC) after anti–PD-1/L1 immunotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10072-10072 ◽  
Author(s):  
Michael K.K. Wong ◽  
Ciara Marie Kelly ◽  
Melissa Amber Burgess ◽  
Karl Lewis ◽  
Jaspreet Singh Grewal ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Response Assessment ◽  
Merkel Cell ◽  
Open Label ◽  
First Response ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Stage 1

10072 Background: MCC is an aggressive neuroendocrine skin cancer with very poor prognosis. Immune checkpoint inhibition was recently shown to benefit some patients (pts). There are few effective treatments (tx) and no standard of care for those who relapse on or are refractory to anti-PD-1/L1 agents (R/R). In p53WT MCC, oncoproteins from the Merkel cell polyomavirus can inhibit p53 tumor suppressor functions via L-MYC/EP400-dependent activation of MDM2. KRT-232, a potent, selective, orally available MDM2i, is being evaluated in pts with p53WTMCC who are R/R to anti-PD-1/L1 tx. Methods: In stage 1 of this open-label, multicenter, phase 2 study (NCT03787602) pts initially received KRT-232 240mg QD days 1-7 of a 21 day (d) cycle (cy). This cohort was closed due to Grade (Gr) 3/4 cytopenias and pts were moved to 240mg QD days 1-5 of a 28d cy to allow for hematologic recovery. Two new arms were opened: 240mg and 180mg QD days 1-5 of a 28d cy. The primary endpoint is objective response rate (ORR) by RECIST 1.1. Secondary endpoints include duration of response, progression-free survival, overall survival, and safety and tolerability of KRT-232. Results: At the time of this analysis, 11 pts were treated with KRT-232: 6 on the 240mg 7/21d, 3 on the 240mg 5/28d and 2 on the 180mg 5/28d schedules. Median age was 66; 46% of pts had ECOG 1 (range 0-1), the median prior lines of systemic therapy was 3 (range 1-4) and 82% had prior radiation tx. Treatment-emergent adverse events (AEs), regardless of grade or causality, were reported in all pts: 55% had Gr 3-4 AEs and 36% had serious AEs (SAEs). The most common AEs included neutropenia (55%), anemia, leukopenia and thrombocytopenia (each 45%), diarrhea, nausea and fatigue (each 36%), and lymphopenia, hypomagnesaemia, lipase increase and sinus tachycardia (each 27%). SAEs were mainly due to cytopenias. One Gr 5 AE of respiratory failure/ascites was attributed to progression. Median time on study was 11.3 wks (range 1.3-20.9). Two of 11 pts on active tx have not yet reached the first response assessment (wk 6). Of the 9 pts who have reached wk 6, 2 PRs and 1 SD (converted to PR at wk 12) were reported. At the second response assessment (wk 12), 2 PRs were reported; one of the PRs at wk 6 has not yet reached wk 12. The ORR was 33% (3/9 pts) . Conclusions: KRT-232 demonstrates promising monotherapy activity in MCC p53WT pts who failed anti-PD-1/L1 tx. This is the first clinical proof-of-concept for inhibiting the MDM2 pathway in MCC. Safety and efficacy continue to inform KRT-232 dose and schedule optimization. Clinical trial information: NCT03787602.

Pembrolizumab (P) in patients (Pts) with colorectal cancer (CRC) with high tumor mutational burden (HTMB): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 133-133 ◽  
Author(s):  
Eyal Meiri ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Pam K. Mangat ◽  
Sagun Shrestha ◽  
...  
Keyword(s):  
Objective Response ◽  
Kidney Injury ◽  
Progression Free Survival ◽  
Tumor Board ◽  
Tumor Mutational Burden ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

133 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with HTMB treated with P are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-1, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had HTMB, defined as ≥9 mutations/megabase (Muts/Mb) by a FoundationOne test (n=26) or other tests (n=2) approved by the Molecular Tumor Board. Pts with MSI-H tumors were ineligible. Dosing of P was 2 mg/kg (n=8) or 200 mg (n=20) IV over 30 mins, every 3 wks. Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16+ wks according to RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight pts enrolled from June 2017 to November 2018; 1 pt was ineligible and excluded. HTMB ranged from 9 to 54 Muts/Mb. Table (N=27) summarizes demographics and outcomes. Tumor MS status was reported stable for 25 pts, ambiguous for 1 pt, and not available for 1 pt. One PR (MS stable and 10 Muts/Mb) and 7 SD16+ were observed for DC and OR rates of 28% (90% CI, 16% to 45%) and 4% (95% CI, 0% to 19%), respectively. 2 pts each had grade 3 AEs at least possibly related to P including abdominal infection, anorexia, colitis, diarrhea, fatigue, nausea, and vomiting; 1 also had SAE of acute kidney injury. Conclusions: Monotherapy with P showed anti-tumor activity in heavily pre-treated CRC pts with HTMB . Additional study is warranted to confirm the efficacy of P in this population. Clinical trial information: NCT02693535. [Table: see text]

scholarly journals CTIM-03. PHASE II STUDY OF REGORAFENIB IN BEVACIZUMAB REFRACTORY RECURRENT GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii33-ii33
Author(s):  
Yasmeen Rauf ◽  
Cathy Schilero ◽  
David Peereboom ◽  
Manmeet Ahluwalia
Keyword(s):  
Dose Escalation ◽  
Therapeutic Option ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Weekly Dose ◽  
Cellular Functions ◽  
Molecule Inhibitor ◽  
Secondary Endpoints ◽  
Magnetic Resonance Imaging Mri

Abstract BACKGROUND Most patients with glioblastoma (GBM) receive bevacizumab as part of their treatment. There is no good therapeutic option after bevacizumab failure. Regorafenib has potent preclinical antitumor activity and long-lasting anti-angiogenic activity as measured by dynamic contrast enhanced (DCE) – magnetic resonance imaging (MRI). Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment. METHODS Patients with progression of GBM after treatment with Bevacizumab will be eligible for the study. Oral administration of Regorafenib at 160 mg once daily will be administered for 3 weeks on /1 week off. Weekly dose escalation of regorafenib from 80 mg to 160 mg/day will be employed as per the Redos strategy. Patients start the treatment 80 mg/day in week 1, with weekly dose escalation to 120 mg in week 2, then 160 mg week in 3 if no significant drug-related toxicities are observed. They will be continued on treatment with Regorafenib 160 md /day till tumor progression or toxicity. They will get MRI brain every 4 weeks during the study. RESULTS Primary endpoint is median Overall survival. Secondary endpoints include progression free survival at 6 months and the median time to progression and objective response rate using the modified RANO criteria. The overall safety and tolerability of regorafenib by CTCAE version 5.0. will also be reported. CONCLUSION This is an ongoing clinical trial.

scholarly journals Phase II study of an oxaliplatin-based regimen for relapsed colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (INSPIRE study)

2021 ◽  
Author(s):  
Keiichiro Ishibashi ◽  
Toru Aoyama ◽  
Masahito Kotaka ◽  
Hironaga Satake ◽  
Yasushi Tsuji ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
First Line ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Peripheral Sensory ◽  
Line Chemotherapy

Abstract Background The aim of this study was to evaluate the efficacy and safety of first-line chemotherapy with re-introduction of oxaliplatin (OX) more than 6 months after adjuvant chemotherapy including OX. Methods Stage II/III colon cancer patients with neuropathies of grade ≤ 1 who relapsed more than 6 months after adjuvant chemotherapy including OX were considered eligible. Eligible patients were treated with 5-fluorouracil, l-leucovorin and OX plus molecularly targeted agents or capecitabine and OX plus bevacizumab (BV) or S-1 and OX plus BV. The primary endpoint was the progression-free survival (PFS), and the secondary endpoints were the overall survival (OS), response rate (RR) and toxicity. Results A total of 50 patients were enrolled between September 2013 and May 2019. Twelve patients received 5-fluorouracil, l-leucovorin and OX (FOLFOX) plus BV, 21 patients received capecitabine and OX plus BV, 10 patients received S-1 and OX plus BV and 7 patients received FOLFOX plus cetuximab or panitumumab. The median PFS was 11.5 months (95% confidence interval [CI] 8.3–16.0), the median OS was 45.4 months (95% CI 37.4–NA), and the RR was 56.0% (95% CI 42.3–68.8). Adverse events of grade ≥ 3 that occurred in ≥ 5% of cases were neutropenia in 6 patients (12%), peripheral sensory neuropathy in 5 patients (10%), diarrhea in 4 patients (8%), hypertension in 4 patients (8%), anorexia in 3 patients (6%) and allergic reactions in 3 patients (6%). Conclusions First-line chemotherapy with re-introduction of OX more than 6 months after adjuvant chemotherapy including OX can be used safely with expected efficacy for relapsed colon cancer patients.

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