ABC-08: A phase Ib, multi-centre, open-label study of a first-in-class nucleotide analogue NUC-1031 in combination with cisplatin in patients with locally advanced/metastatic biliary tract cancers.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS544-TPS544 ◽  
Author(s):  
Mairead Geraldine McNamara ◽  
John A. Bridgewater ◽  
Daniel H. Palmer ◽  
Harpreet Singh Wasan ◽  
David Ryder ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Standard Dose ◽  
Performance Status ◽  
Locally Advanced ◽  
Clinical Activity ◽  
Cancer Resistance ◽  
Open Label ◽  
Ecog Performance Status ◽  
Biliary Tract Cancers ◽  
Phase Ib

TPS544 Background: The UK ABC-02 study established cisplatin and gemcitabine as the reference regimen for first-line treatment of patients (pts) with advanced biliary tract cancers (BTCs) (median overall survival (OS): 11.7 months). No clinical studies since ABC-02 have reported an extension in OS, and therefore effective new agents/combinations are required. NUC-1031 was designed to improve on gemcitabine’s relatively poor efficacy by overcoming its associated key cancer resistance mechanisms, through cellular uptake independent of nucleoside transporters, activation independent of deoxycytidine kinase and protection from cytidine deaminase inactivation, resulting in over 200x the intracellular levels of the anti-cancer metabolite, dFdCTP, greater stability and reduction in the generation of toxic metabolites. NUC-1031 showed activity as monotherapy in a phase I/II study in 7 pts with BTC, refractory to all standard treatments (Blagden et al ASCO 2015; abstract 2514). Methods: ABC-08 is a multi-centre phase Ib study of NUC-1031 combined with cisplatin in pts with non-resectable or recurrent/metastatic cholangiocarcinoma, gallbladder or ampullary carcinoma, aged ≥18 years with an ECOG performance status of 0-1, who have received no prior systemic therapy. The starting dose for NUC-1031 is 625 mg/m2 administered IV on days 1 and 8 in combination with cisplatin (standard dose of 25 mg/m2) (21 day schedule). The dose will be escalated sequentially in cohorts of 3-6 pts using an accelerated titration procedure (725mg/m2, 825mg/m2, 925mg/m2). Treatment will continue until intolerable toxicity/progressive disease. The primary endpoints are safety and RP2D. Secondary endpoints are progression-free survival, OS, response rate and pharmacokinetic endpoints, including assessments of multiple plasma and intracellular analytes: NUC-1031, cisplatin, dFdC, dFdCMP, dFdCDP, dFdCTP and dFdU, and will be correlated with safety profile and clinical activity. Planned accrual is 15-24 pts over 2 years. Cohort 1 has been completed without dose-limiting toxicities. Enrolment to cohort 2 is on-going. Clinical trial information: NCT02351765.

Avelumab (MSB0010718C), an anti-PD-L1 antibody, as a third-line treatment in patients with advanced gastric or gastroesophageal junction cancer: A phase Ib JAVELIN Solid Tumor trial.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS188-TPS188 ◽  
Author(s):  
Do-Youn Oh ◽  
Albert C. Lockhart ◽  
Deborah Jean Lee Wong ◽  
Matthew Hiram Taylor ◽  
Marcis Bajars ◽  
...  
Keyword(s):  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Her2 Status ◽  
Open Label ◽  
Ecog Performance Status ◽  
Phase Ib ◽  
Prior Therapy ◽  
Recist 1.1

TPS188 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. The phase Ib study (NCT01772004) is an open-label, parallel-group expansion trial in patients (pts) with locally advanced or metastatic (LA/M) solid tumors that includes a heavily pretreated cohort of pts with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) to evaluate safety and efficacy of avelumab in the 3rd-line setting. Prior to adding this 3rd-line cohort, this trial had enrolled a separate cohort with advanced GC/GEJ who had received prior 1st-line chemotherapy (Chung et al, ECC 2015). Methods: This trial cohort is enrolling pts with histologically confirmed unresectable LA/M GC/GEJ who have been previously treated with 1st-line combination chemotherapy and 2nd-line ramucirumab, alone or in combination, and whose disease has progressed during or after ramucirumab treatment. Pts who have received prior treatment with trastuzumab and pts with HER2+ status are allowed. Eligible pts also must have tumor archival material or fresh biopsy, an ECOG performance status of 0 or 1 at the time of trial entry, and disease with ≥ 1 measurable lesion according to RECIST 1.1. Exclusions include prior therapy with immune checkpoint drugs or history of autoimmune disease. Up to 150 eligible pts will receive avelumab at 10 mg/kg as an IV infusion Q2W. Treatment will continue until disease progression, unacceptable toxicity, or any criterion for withdrawal occurs. Primary endpoint is confirmed best overall response (RECIST 1.1) as adjudicated by an IERC. Secondary objectives include assessment of progression-free survival, overall survival, and immune-related efficacy assessments. Association between tumor PD-L1 expression and efficacy will be evaluated. Adverse events will be assessed and graded according to NCI-CTCAE v4.0. Tumor evaluation will be performed every 6 wks until progression. Enrollment in this cohort began in June 2015. *Proposed INN Clinical trial information: NCT01772004.

Phase IB study of induction chemotherapy with XELOX, followed by radiation therapy, carboplatin, and everolimus in patients with locally advanced esophageal cancer (EC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15607-e15607
Author(s):  
Nabil F. Saba ◽  
Seth D Force ◽  
Charles A. Staley ◽  
Felix G Fernandez ◽  
Field F. Willingham ◽  
...  
Keyword(s):  
Disease Progression ◽  
Dose Level ◽  
Performance Status ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
R0 Resection ◽  
Ecog Performance Status ◽  
Phase Ib ◽  
Poor Tolerance

e15607 Background: Preclinical studies have shown synergy between everolimus, an mTOR inhibitor, radiation and platinum agents in EC. We conducted a multi-institutional phase IB trial to determine the recommended phase II dose (RP2D) of concurrent everolimus with carboplatin and radiation in non-metastatic EC pts. Methods: Patients with untreated, localized EC and ECOG performance status 0-1 were eligible. Following two cycles of induction Capecitabine/Oxaliplatin (XELOX), pts without evidence of disease progression, received concurrent chemoradiation (total dose: 50.4Gy in 28 fractions), weekly carboplatin (AUC = 2), and escalating doses of everolimus. A standard 3+3 dose escalation design was used. Results: Nineteen patients were enrolled. There were two screen failures (thrombocytopenia, metastases) and 4 pts were removed due to poor tolerance of XELOX (2 pts) or disease progression (2 pts). A total of 13 pts with stage II/III (6/7) EC completed concurrent therapy. Median age 58 (44-71yrs), 85% males; all had adenocarcinoma deemed resectable. One pt at dose level 1 (2.5 mg/QOD), was replaced due to ongoing anxiety. One of 6 pts had a DLT (bowel ischemia). At dose level 2 (2.5mg/QD), 2 out of 6 patients had a DLT (fever with neutropenia and nausea). The RP2D of everolimus was 2.5 mg QOD. Clinically relevant ≥ grade 3 toxicities included lymphopenia (25%), dehydration (12%), fatigue, leukopenia, hyponatremia, abdominal pain, vomiting (each 6%). R0 resection was achieved in 100%; a pathologic response rate (RR) of 40% and a pathologic complete response (pCR) rate of 23% were observed. The 2-year PFS and OS were 50% and 49.6% respectively. Conclusions: The RP2D of everolimus with concurrent weekly carboplatin and radiation is 2.5 mg QOD. Despite the 100% R0 resection rate, the pCR and OS rates were within the expected historical controls. (The study was funded by Novartis Pharmaceuticals) Clinical trial information: NCT01490749.

Safety and efficacy of modified FOLFIRINOX in pancreatic cancer: A retrospective experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14614-e14614 ◽  
Author(s):  
Hemchandra Mahaseth ◽  
John S. Kauh ◽  
Edith Brutcher ◽  
Natalyn Nicole Hawk ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Emory University ◽  
Grade 3

e14614 Background: Conroy et al reported a significant improvement in overall survival of patients with metastatic pancreatic cancer treated with FOLFIRINOX compared to single agent gemcitabine. The regimen was associated with significant grade 3/ 4 toxicities, such as myelosuppression(46%), fatigue(24%), vomiting(15%) and diarrhea (13%). In order to improve the toxicity profile, we have modified FOLFIRINOX (mFOLFIRINOX) regimen by removing the bolus 5-FU and adding the routine use of growth factor prophylaxis. We present our experience with mFOLFIRINOX in patients with locally advanced or metastatic pancreatic cancer. Methods: After obtaining IRB approval, patients with a diagnosis of pancreatic cancer were identified from the Emory University tumor registry. Twenty eight patients who received at least one dose of mFOLFIRINOX (5-FU 2400 mg/m2 CIVI over 46 hours, leucovorin 400 mg/m2, oxaliplatin 85 mg/m2, irinotecan 180 mg/m2 and pegfilgrastim 6 mg every two weeks ) were selected and their charts were retrospectively reviewed for safety, response, and survival. Results: Of 28 patients, 14 (50%) were male, 18 (64%) white, 8 (29%) black and other 2(7%). Median age was 63 (50-75) and ECOG performance status 0-1. Nineteen (68%) patients had primary tumor located in head of pancreas. Eight patients (29%) experienced grade 3/4 toxicities, i.e., nausea/vomiting (11%), diarrhea (11%), fatigue (11%), neuropathy (4%), neutropenia (4%), thrombocytopenia(4%), and sepsis not-related to neutropenia (4%). No grade 3/4 anemia or febrile neutropenia was noted. mFOLFIRINOX controlled the disease in 20 patients (71%) with 2 CR, 4 PR and 14 SD. With a median follow up of 5.5 months, median overall or progression free survival is not reached. Two patients have died and six patients have progressed. Conclusions: Modified FOLFIRINOX is well tolerated in this US population. The clinical activity appears very promising with majority of patients being free of progression.

Targeting HER2 (ERBB2) mutation-positive advanced biliary tract cancers with neratinib: Results from the phase II SUMMIT ‘basket’ trial.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 320-320
Author(s):  
James J. Harding ◽  
James M. Cleary ◽  
David I. Quinn ◽  
Irene Braña ◽  
Victor Moreno ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Study Drug ◽  
Standards Of Care ◽  
Clinical Activity ◽  
Genomic Profiling ◽  
Open Label ◽  
Biliary Tract Cancers

320 Background: Genomic profiling studies have reported somatic HER2 mutations in ~2–5% of biliary tract cancers (BTC). Clinical data from the SUMMIT study demonstrate that neratinib, a pan-HER irreversible tyrosine kinase inhibitor, has encouraging clinical activity in multiple types of HER2-mutant solid tumor malignancies. Methods: SUMMIT is a multi-histology, open-label, phase II ‘basket’ study of neratinib in patients with somatic HER2 mutations (ClinicalTrials.gov NCT01953926). Patients with activating somatic HER2 mutations with different histologies, including BTC, received neratinib monotherapy (240 mg oral daily). Loperamide prophylaxis was mandatory during cycle 1. Efficacy endpoints: objective response rate (ORR, RECIST v1.1); clinical benefit rate (CBR); duration of response; progression-free survival (PFS). Adverse events (AEs) were assessed by CTCAE v4.0. Genomic profiling from fresh/archival tumor tissues and/or plasma cfDNA was performed retrospectively by next-generation sequencing (MSK-IMPACT). Results: As of 3-Sep-2020, 25 patients with HER2-mutant BTC were enrolled: gallbladder (40%); intrahepatic (24%); extrahepatic (20%); ampulla of Vater (16%). 68% of patients received ≥2 systemic regimens (96% received prior gemcitabine-based regimens). The S310F/Y variant accounted for nearly half of HER2 mutations (n=11). Other HER2 mutations: V777L (n=5); L755S (n=2); V842I (n=2); R678Q (n=2). Confirmed ORR in 25 evaluable patients was 12% (95% CI 3–31%) and CBR was 20% (95% CI 7–41%), including 3 confirmed PRs and 2 patients with SD for ≥16 weeks. Tumor shrinkage was observed in multiple HER2-activating mutations and enriched in gallbladder and extrahepatic subtypes of BTC. Median PFS was 2.8 (95% CI 1.1–3.7) months; median overall survival (OS) was 5.4 (95% CI 3.7–11.7) months. Nine (36%) patients (3 of whom with ECOG PS 2) came off study within 28 (range 6–47) days of treatment due to clinical deterioration (unrelated to study drug) followed by death. The most common treatment-related AEs (any grade) were diarrhea (56%) and vomiting (48%). Diarrhea was the most common Grade 3 event (24%); 4 patients (16%) required a neratinib dose reduction; no patients discontinued treatment due to diarrhea. Conclusions: Neratinib is safe and tolerable in patients with advanced BTC patients and somatic HER2 mutations. The antitumor activity of neratinib appears comparable to current standards of care, with similar PFS and OS in heavily pretreated patients. Analysis of co-occurring oncogenic mutations and response is ongoing, and consideration is being given to neratinib-based combination regimens to further improve outcomes in this setting. Clinical trial information: NCT01953926.

Health-related quality of life (HRQoL) in patients (pts) with locally advanced basal cell carcinoma (laBCC) treated with cemiplimab: Analysis of a phase II, open-label clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9566-9566
Author(s):  
Alexander J. Stratigos ◽  
Chieh-I Chen ◽  
Cristina Ivanescu ◽  
Karl D. Lewis ◽  
Ketty Peris ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Repeated Measures ◽  
Performance Status ◽  
Locally Advanced ◽  
Symptom Burden ◽  
Open Label ◽  
Ecog Performance Status ◽  
Meaningful Improvement ◽  
Responder Analysis ◽  
Eortc Qlq

9566 Background: Cemiplimab-rwlc is the first immunotherapy to receive approval in the US, fully for pts with laBCC and accelerated for metastatic BCC, post hedgehog inhibitors or for whom hedgehog inhibitors are not appropriate. Cemiplimab resulted in clinically meaningful anti-tumor activity in pts with laBCC who progressed on or were intolerant to hedgehog inhibitor therapy (NCT03132636). This analysis evaluated HRQoL in these pts. Methods: Adults with laBCC and ECOG performance status ≤1 (n=84) received IV cemiplimab 350 mg Q3W for up to 9 treatment cycles. At baseline (BL) and day 1 of each cycle (C), pts completed EORTC QLQ-C30 and SKINDEX-16 questionnaires that assess Global Health Status (GHS)/QoL, functioning, and BCC-related symptoms. Mixed-effects repeated measures (MMRM) models were used to estimate least squares (LS) mean (standard error [SE]) change from BL during treatment (i.e., across C2 to C9); changes ≥|10| points were considered clinically meaningful. Responder analyses were conducted in pts with non-missing data from BL to determine the proportions with clinically meaningful improvement or deterioration, or stability on QLQ-C30 and SKINDEX-16 at C2 and C9; a 10-point threshold was considered meaningful for both instruments. Results: BL scores showed moderate to high levels of functioning and low symptom burden. In MMRM models, overall changes from BL on QLQ-C30 indicated stability for GHS/QoL and all scales except for clinically meaningful worsening of fatigue (LS mean [SE] change 12.5 [3.9]; P<.05). In responder analysis, the majority of pts reported clinically meaningful improvement or stability at C2 and C9 on all QLQ-C30 functioning scales and the key symptom of pain but not fatigue (Table). On SKINDEX-16, MMRM models showed clinically meaningful improvement on the emotional subscale (LS mean [SE] change –13.2 [3.9]; P<.05) and stability on the symptom and functional subscales. Responder analysis showed clinically meaningful improvements or stability across the SKINDEX-16 subscales in approximately 80% of pts at C2, and 70–80% of pts at C9. Conclusions: In laBCC pts treated with cemiplimab, the majority reported clinically meaningful improvement or stability in GHS/QoL and functional status while maintaining a low symptom burden except for fatigue. Clinical trial information: NCT03132636. [Table: see text]

Efficacy and safety of oral MEK162 in patients with locally advanced and unresectable or metastatic cutaneous melanoma harboring BRAFV600 or NRAS mutations.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8511-8511 ◽  
Author(s):  
Paolo Antonio Ascierto ◽  
Carola Berking ◽  
Sanjiv S Agarwala ◽  
Dirk Schadendorf ◽  
Carla Van Herpen ◽  
...  
Keyword(s):  
Median Time ◽  
Cutaneous Melanoma ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Clinical Activity ◽  
Open Label ◽  
Good Tolerability ◽  
Prior Therapy ◽  
Open Label Phase

8511 Background: BRAF and NRAS mutations occur in 50-60% and 15-20% of cutaneous melanomas, respectively. MEK162, a selective inhibitor of the kinases MEK1 and MEK2, has shown pre-clinical activity in BRAF and NRAS mutant (mt) melanoma models. This open label, phase II study assessed the antitumor activity of MEK162 in patients (pts) with BRAFV600 and NRAS mt advanced cutaneous melanoma. Methods: MEK162 was administered orally at a starting dose of 45 mg twice daily. Treatment was until unacceptable toxicity, disease progression (PD) or investigator or patient refusal. Tumor response was assessed by CT imaging every 8 weeks (RECIST 1.0) until PD. Results: As of 16 Sept 2011, the full analysis and safety populations comprised 66 pts: 42 BRAF mt and 24 NRAS mt. Median age 58.0 years; 57.6% male; 72.7% WHO performance status 0. All NRAS pts and all but 2 BRAF (1 each stage IIIB and IIIC) pts had stage IV disease, and 87.5% of NRAS pts and 66.7% of BRAF pts had received prior therapy at study entry. Median time from 1st diagnosis to 1st dose of drug was 40.4 months. Median time on study was 10.4 and 8.5 weeks for the BRAF and NRAS arms. Relative dose intensities of 80–<100% were received by 71.4% and 70.8% of pts, respectively. Among 29 BRAF mt and 13 NRAS mt pts evaluable for efficacy, 1 confirmed and 6 unconfirmed partial responses (PRs) and 9 pts with stable disease (SD) were recorded in the BRAF arm and 2 confirmed PRs, 1 unconfirmed PR and 4 pts with SD recorded in the NRAS arm. Common treatment–related adverse events (AEs), all grades (Gs) and all pts, were rash (40.9%), diarrhea (33.3%), acneiform dermatitis (27.3%), creatine phosphokinase (CK) elevation (25.8%), fatigue (18.2%) and peripheral edema (21.2%). Central serous retinopathy-like retinal events (G 1/2 only) were reported in 8 (12.1%) pts (6 G1, 2 G2). All retinal events were reversible. G3/4 AEs in >1pt were diarrhea (4.5%) and CK elevation (15.2%). 5 pts discontinued due to toxicity. 34 pts are ongoing with more responses under current review. Conclusions: MEK162 showed clinical activity and good tolerability in pts with BRAF and NRAS mt advanced melanoma. This is the 1st targeted therapy to show activity in pts with NRAS mt melanoma.

Phase Ib/II study of eribulin mesylate administered in combination with gemcitabine/cisplatin as first-line therapy for locally advanced or metastatic bladder cancer: Phase Ib results.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 273-273 ◽  
Author(s):  
Nicholas J. Vogelzang ◽  
Paul Conkling ◽  
Ignacio Duran ◽  
José Pablo Maroto ◽  
Manuel Modiano ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Standard Dose ◽  
Locally Advanced ◽  
Clinical Activity ◽  
Limiting Factor ◽  
Hematologic Toxicity ◽  
Synthetic Analog ◽  
Eribulin Mesylate ◽  
Phase Ib ◽  
Overall Response

273 Background: Eribulin mesylate (E) is a synthetic analog of the natural, marine-sponge product halichondrin B. A phase (Ph) II study of E monotherapy in urothelial carcinoma with no prior cytotoxic therapy for advanced disease reported an overall response rate of 38% (95% CI: 23%, 54%; Quinn et al ASCO 2010, abstract 4539). Therefore, we combined E with gemcitabine (G) and cisplatin (C) to assess the feasibility, safety, and preliminary activity of the combination, in patients (pts) with advanced bladder cancer. This is an open-label, multicenter study consisting of a Ph Ib and Ph II portion. Methods: In the Ph Ib portion, three ascending doses of E were to be administered IV on days 1 and 8 q21d to determine the MTD with standard doses of G (1000 mg/m2, days 1 and 8 q21d) and C (70 mg/m2, day 1). In Ph II, pts are randomized 1:1 to E plus G/C, or G/C alone. Results: Nine pts (median age: 59 years; 7 male/2 female) entered Ph Ib. Pts received E 0.7 mg/m2 (n=3) or 1.0 mg/m2 (n=6), with standard dose G/C. Thirty-four cycles were given (2 pts are ongoing). One dose-limiting toxicity (DLT) was observed at 1.0 mg/m2 (Gr 4 thrombocytopenia). The 1.4 mg/m2 dose of E was not explored due to an investigator consensus that, with that dose, the probability of DLTs (severe hematologic toxicity) developing was high. Thus, the MTD was not achieved or defined. The recommended Ph II dose (RP2D) of E in combination with G/C was established as 1.0 mg/m2. Most common adverse events at the RP2D were nausea (83%), neutropenia (83%), fatigue (83%), thrombocytopenia (83%), anemia (83%), and anorexia (50%). Best responses at 1.0 mg/m2 were 1 complete response (CR) (unconfirmed) and 4 partial responses (PR) (all confirmed). Overall response for both cohorts was 89% – 2 CRs (1 confirmed, 1 unconfirmed) and 6 PRs (4 confirmed, 2 unconfirmed). Six pts have been randomized into the Ph II portion of the study to date. Conclusions: E combined with standard G/C chemotherapy is feasible and has encouraging clinical activity. Hematologic toxicity is the main limiting factor.

Phase III trial of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 249-249 ◽  
Author(s):  
Calin Cainap ◽  
Shukui Qin ◽  
Wen-Tsung Huang ◽  
Ik-Joo Chung ◽  
Hongming Pan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Vascular Invasion ◽  
Performance Status ◽  
Objective Response ◽  
Phase Iii ◽  
Clinical Activity ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Ecog Performance Status ◽  
Advanced Hcc

249 Background: Linifanib (ABT-869; Lin) is a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinase families. In a phase II trial in patients (pts) with advanced HCC, Lin showed clinical activity (objective response rate [ORR] 10.5% in Child-Pugh A [CPA] pts). This open-label, global phase 3 trial evaluated Lin versus sorafenib (Sor) as first-line therapy in pts with advanced CPA HCC (NCT01009593). Methods: Pts were randomized 1:1 to Lin 17.5 mg QD or Sor 400 mg BID and stratified by region (non-Asia/Japan/rest of Asia), ECOG performance status (0/1), vascular invasion or extrahepatic spread (yes/no) and HBV infection (yes/no). The primary efficacy endpoint was overall survival (OS); both non-inferiority (margin 1.0491) and superiority hypotheses were to be tested. Secondary efficacy endpoints included time to progression (TTP) and ORR, using RECIST v1.1. AE severity was graded using NCI-CTCAE v4.0. Results: 1035 pts (median age 60 y, 68% Asian, 65% ECOG 0, 49% HBV, 70% vascular invasion or extrahepatic spread) were randomized at 149 sites in 26 countries. Hazard ratio (HR) for OS was 1.046 (95% CI: 0.896, 1.221). Median OS (95% CI) was 9.1 months (m) (8.1, 10.2) on Lin and 9.8 m (8.3, 11.0) on Sor. For all pre-specifed subgroup analyses, OS HRs ranged from 0.793-1.119, and the 95% CI contained 1.0. TTP HR was 0.759 (95% CI: 0.643, 0.895; p=0.001) favoring Lin. Median TTP (95% CI) was 5.4 m (4.2, 5.6) on Lin and 4.0 m (2.8. 4.2) on Sor. ORR was 13.0% on Lin and 6.9% on Sor. Grade 3/4 AEs, serious AEs and AEs leading to discontinuations, dose interruptions and reductions were more frequent on Lin versus Sor (all p<0.001). Conclusions: Lin and Sor resulted in similar OS in advanced HCC. Predefined superiority and non-inferiority OS boundaries were not met for Lin. Secondary endpoints (TTP and ORR) favored Lin while safety results favored Sor. Clinical trial information: NCT01009593.

Characteristics and treatment patterns of elderly patients with biliary tract cancers.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 459-459
Author(s):  
Ji Hyun Yang ◽  
In-Ho Kim ◽  
Joon Won Jeong ◽  
Sang Mi Ro ◽  
Myung Ah Lee
Keyword(s):  
Elderly Patients ◽  
Supportive Care ◽  
Biliary Tract ◽  
Early Stage ◽  
Performance Status ◽  
Locally Advanced ◽  
Best Supportive Care ◽  
Poor Performance Status ◽  
Biliary Tract Cancers ◽  
The Mean

459 Background: Biliary tract cancers do not respond well to multipmodal treatment and generally show poor prognosis, and this may be a reason to make elderly patient consider best supportive care only. Methods: We reviewed 108 elderly patients of 80 years of age or older who diagnosed as biliary tract cancers from 2008 to 2014 at Seoul St. Mary's Hospital, Korea. Results: The mean age was 83.76 years ranging from 80 to 100. The patients included 24 intrahepatic(22.2%), 17 common bile duct(15.7%), 21 perihilar(19.4%), 37 gall bladder(34.3%), and 9 Ampulla of Vater(8.3%) cancers. 47 patients (43.5%) was initially resectable and 19(40.4%) of them underwent curative surgery, 17(36.2%) had percutaneous or endoscopic biliay drainage, and 11(23.4%) had best supportive care only. Mean survival was 29.8 months, 15.1 months, and 12 months, following the above treatment, respectively(p = 0.004). The mean hospitalized time for the curatively resected patients was 9.8 days. One died of traumatic SAH after surgery, 2 underwent adjuvant chemotherapy, and 10 experienced recurrence. Unresectable patients included 13 (12%) with locally advanced disease and 48 (44.4%) with distant metastasis. Among them, 4(6.6%) received palliative radiotherapy or chemotherapy, 30(49.2%) had biliary drainage, and 27(44.3%) had just best supportive care. Mean survival was 10.2 months, 7.3 months, and 3.6 months, respectively(p = 0.109). One with radiotherapy did not completed his treatment course due to intolerance. Three received chemotherapy with dose reduction from 75% to 70% considering their old age and poor performance status. Among those patients, 1 patient with stage IV intrahepatic cholangiocarcinoma showed partial response at 1st line of chemotherapy and had received totally 3 lines of chemotherapy. He survived 16.4 months. Conclusions: Elderly patients with early stage cancers who undewent curative resection and some selected advanced stage patients with palliative chemotherapy showed good response and survival improvement. There should be careful decision making for the management for geriatric biliary tract cancer patients and further investigations are needed to find more predictive factors.

A phase Ib/II study of cetuximab and pembrolizumab in RAS-wt mCRC.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 834-834 ◽  
Author(s):  
Patrick McKay Boland ◽  
Alan Hutson ◽  
Orla Maguire ◽  
Hans Minderman ◽  
Christos Fountzilas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Data ◽  
Performance Status ◽  
Hepatic Metastases ◽  
Fixed Dose ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Phase Ib ◽  
Grade 3

834 Background: Cetuximab is a chimeric IgG1 anti-EGFR monoclonal antibody approved in RAS-wt metastatic colorectal cancer (mCRC). Pre-clinical data have suggested that cetuximab triggers immunogenic cell death and support an immunologic basis of activity. Small clinical data sets demonstrate that EGFR-based therapy preferentially increases TILs in colorectal hepatic metastases. This Phase Ib/II study was designed to assess the safety and clinical activity of cetuximab and pembrolizumab in metastatic colorectal cancer. Methods: Eligible pts were those with RAS-wt mCRC, ECOG performance status (PS) 0-2, with at least 1 prior line of therapy for advanced stage disease, and no prior treatment with an anti-EGFR antibody. The phase Ib study was designed as a safety lead-in with a de-escalation design. Pembrolizumab was administered at a fixed dose of 200 mg q3week with standard cetuximab dosing (400 mg/m2 loading dose, followed by 250 mg/m2 weekly). DLTs were defined as any ≥ grade 3 clinically significant toxicity which is possibly related and occurs within the first 6 weeks of therapy. For rash and hypomagnesemia only ≥ grade 4 toxicities were considered DLTs. Correlative serial biopsies were performed at baseline and at 9 weeks. Results: 9 patients, ages 33-73, were enrolled onto the Phase Ib study between 8/10/16 and 11/2/16. No DLTs were observed. The most common AEs of any cause observed were xerosis, dermatitis acneiform rash, hypomagnesemia, vomiting, and fatigue. ≥ Grade 3 toxicities were uncommon, but included hypomagnesemia (3), rash (1), urticaria (1), hypocalcemia (1), alk phos elevation (1), and ascites (1). 6/9 patients achieved stable disease lasting ≥ 16 weeks. Conclusions: The combination of cetuximab and pembrolizumab is well-tolerated in this study and can be administered at full dosages. Though hypomagnesemia appears prominent, no additional emergent AEs have been observed during or following the DLT period. The associated ongoing phase II study will enroll an additional 33 patients to assess the true efficacy of this regimen with dual primary endpoints of ORR and 6 month PFS. Clinical trial information: NCT02713373.

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