Nivolumab (NIVO) + ipilimumab (IPI) + cabozantinib (CABO) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 478-478 ◽  
Author(s):  
Thomas Yau ◽  
Vittorina Zagonel ◽  
Armando Santoro ◽  
Mirelis Acosta-Rivera ◽  
Su Pin Choo ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
The United States ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Pivotal Phase ◽  
Primary Endpoints ◽  
Tolerability Data ◽  
Grade 3

478 Background: The programmed death-1 inhibitor NIVO had durable responses and a manageable safety profile in pts with aHCC in CheckMate 040 (NCT01658878; El-Khoueiry et al. Lancet 2017) and is approved in the United States, Canada, Australia, and elsewhere for sorafenib (SOR)-treated pts with aHCC. In another CheckMate 040 cohort, NIVO + IPI combination therapy had durable responses in SOR-treated pts with aHCC, with objective response rates (ORRs) > 30% in each dosing arm (Yau et al. J Clin Oncol 2019). CABO is also approved for SOR-treated pts with aHCC; a pivotal phase 3 trial reported median overall survival (OS) of 10.2 mo (Abou-Alfa et al. N Engl J Med 2018). This is the first report of efficacy and safety of NIVO + CABO +/- IPI (doublet and triplet) combinations in pts with aHCC. Methods: SOR-naive or -experienced pts with aHCC were randomized to 2 arms: [1] NIVO 240 mg Q2W + CABO 40 mg daily or [2] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W + CABO 40 mg daily. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included ORR (investigator assessed using RECIST v1.1) and safety/tolerability. Data cutoff was January 2019. Results: 71 pts were randomized to NIVO + CABO (n = 36) or NIVO + IPI + CABO (n = 35). Investigator-assessed ORR was 17% (6 pts with partial response [PR]) in the NIVO + CABO arm and 26% (9 pts with PR) in the NIVO + IPI + CABO arm. Disease control rate was 81% for the NIVO + CABO arm and 83% for the NIVO + IPI + CABO arm; median progression-free survival was 5.5 mo for the NIVO + CABO arm and 6.8 mo for the NIVO + IPI + CABO arm. Median OS was not reached in either arm. Grade 3-4 treatment-related adverse events (TRAEs) were reported in 15 pts (42%) in the NIVO + CABO arm and 25 pts (71%) in the NIVO + IPI + CABO arm and led to discontinuation in 1 (3%) and 7 (20%) pts, respectively. No new safety signals were observed in either arm. Updated data describing the efficacy and safety of the combinations will be shown. Conclusions: In pts with aHCC, NIVO + CABO +/- IPI combination therapy led to clinically meaningful responses. Although the triplet had a higher rate of TRAEs observed than the doublet regimen, the majority of AEs were manageable and reversible. Clinical trial information: NCT01658878.

Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Subgroup analyses from CheckMate 040.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
Aiwu Ruth He ◽  
Thomas Yau ◽  
Chiun Hsu ◽  
Yoon-Koo Kang ◽  
Tae-You Kim ◽  
...  
Keyword(s):  
Disease Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
The United States ◽  
Advanced Hepatocellular Carcinoma ◽  
Subgroup Analyses ◽  
Duration Of Response ◽  
Previously Treated ◽  
Grade 3

512 Background: NIVO monotherapy is approved in the United States and other countries for pts with HCC treated with sorafenib (SOR) based on CheckMate 040 (NCT01658878) results, which reported 14% objective response rate (ORR) and 16-month median overall survival (mOS; El-Khoueiry et al. Lancet 2017). Primary efficacy and safety of NIVO + IPI in pts with aHCC previously treated with SOR were presented recently (Yau et al. J Clin Oncol 2019). Here, we will present subgroup analyses from this study. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety/tolerability, ORR, and duration of response (DOR; investigator assessment per RECIST v1.1). Key secondary endpoints included disease control rate (DCR), OS, and progression-free survival (blinded independent central review [BICR] per RECIST v1.1); key exploratory endpoints included ORR (BICR per RECIST v1.1). Data cutoff was January 2019. Results: A total of 148 pts were randomized. Minimum OS follow-up from last pt randomization date to data cutoff was 28 months. At baseline, 34% of all pts had vascular invasion; 82% had extrahepatic spread; and 91% had Barcelona Clinic Liver Cancer stage C; 84% discontinued SOR because of disease progression and 14% because of toxicity. For all treated pts, ORR was 31% (7 had complete response), with median DOR of 17 months; DCR was 49%; the 30-month OS rate was 37%. NIVO + IPI was well tolerated; 38% of pts had grade 3–4 treatment-related adverse events (TRAEs; most common any grade: pruritus and rash; most common grade 3–4: aspartate aminotransferase increase and lipase increase); 5% had grade 3–4 TRAEs leading to discontinuation. Subgroup analyses based on duration of prior SOR therapy and other pt characteristics will be presented. Conclusions: NIVO + IPI led to clinically meaningful benefits, with a manageable safety profile in pts previously treated with SOR. NIVO + IPI may provide a new treatment option for these pts. Clinical trial information: NCT01658878.

scholarly journals Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: A Subgroup Analysis of Asian Patients in the Phase 3 KEYNOTE-240 Trial

Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Masatoshi Kudo ◽  
Ho Yeong Lim ◽  
Ann-Lii Cheng ◽  
Yee Chao ◽  
Thomas Yau ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
The Philippines ◽  
Advanced Hepatocellular Carcinoma ◽  
Asian Patients ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Grade 3

<b><i>Introduction:</i></b> KEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described. <b><i>Methods:</i></b> Adults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety. <b><i>Results:</i></b> The Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6–4.1) versus 1.4 months (95% CI 1.4–2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32–0.70). The median OS was 13.8 months (95% CI 10.1–16.9) for pembrolizumab versus 8.3 months (95% CI 6.3–11.8) for placebo (HR 0.55; 95% CI 0.37–0.80). ORR was 20.6% (95% CI 13.4–29.5) for pembrolizumab versus 2.0% (95% CI 0.1–10.6) for placebo (difference: 18.5%; 95% CI 8.3–27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3–5 TRAEs, respectively. No treatment-related deaths occurred. <b><i>Conclusion:</i></b> Pembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Effective Treatment Option ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

Sorafenib versus cytotoxic chemotherapy for patients with advanced hepatocellular carcinoma: A retrospective, single-institution study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 339-339
Author(s):  
S. Lee ◽  
S. Yoon ◽  
S. Shin ◽  
H. Choi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cytotoxic Chemotherapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Chemotherapy Group ◽  
Sorafenib Group ◽  
The Difference ◽  
Grade 3 ◽  
Novel Target

339 Background: Prior to the sorafenib era, most of the advanced hepatocellular carcinoma (HCC) patients had to rely only on conventional cytotoxic chemotherapy. But the introduction of sorafenib in 2008 had given HCC patients additional option for their treatment. However, given that sorafenib has been a nonreimbursable drug under the Korea public health system, most of treatment strategy has largely been determined by patients' affordability of the drug rather than by difference in efficacy and toxicity of the two treatments. Therefore, we compared the efficacy and toxicity of the two treatments by observing HCC patients. Methods: From January 2002 to December 2009, 173 patients with unresectable HCC had been retrospectively analyzed. Among them, 44 (25.4%) had been treated with sorafenib and the remaining had received cytotoxic chemotherapy. We evaluated objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: The median OS of sorafenib group was 23.0 weeks (95% CI, 8.1-37.9) vs. 43.6 weeks (95% CI, 34.0-37.9) for cytotoxic chemotherapy group. The median PFS for sorafenib group was 11.1 weeks (95% CI, 6.5-15.8) versus 12.4 weeks (95% CI, 8.1-16.7) for cytotoxic chemotherapy group. However, the difference in both findings had not been statistically significant (p=0.105 and p=0.496, respectively). ORR and DCR for sorafenib group were 2.3% and 52.3% versus 6.2% and 43.4% for cytotoxic chemotherapy group, respectively. Patients treated with chemotherapy had shown higher frequencies of grade 3 or 4 neutropenia, 19.7%, (vs. 0% for sorafenib). However, the group with sorafenib had reported a higher rate of all grade dermatologic toxicities such as hand-foot skin reaction, rash and pruritus. Conclusions: Our analysis indicates that efficacy of conventional chemotherapy is not inferior to that of sorafenib. Further research including novel target agent and cytotoxic chemotherapy is needed to improve clinical outcomes for advanced HCC. No significant financial relationships to disclose.

Efficacy and safety of sunitinib (SU) in patients (pts) with metastatic renal cell carcinoma (mRCC) and lung metastases (mets) only at baseline.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15098-e15098
Author(s):  
Nobuo Shinohara ◽  
Hideyuki Akaza ◽  
Yoshihiko Tomita ◽  
Takeshi Yuasa ◽  
Hiroyuki Fujimoto ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Objective Response ◽  
White Blood Cells ◽  
Progression Free Survival ◽  
Rank Test ◽  
Efficacy And Safety ◽  
Kaplan Meier ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Grade 3

e15098 Background: The lungs may be the sole site of mets in RCC.In this retrospective analysis, we analyzed the efficacy and safety of SU in mRCC pts from a global phase (ph) III study and a Japanese ph II study who had lung mets only at baseline. Methods: In the ph III study, treatment (Tx)-naïve mRCC pts were randomized 1:1 to SU 50 mg/d on a 4-weeks-on-2-weeks-off schedule (n=375) or interferon-a (IFN) 9 MU subcutaneously TIW (n=360). In the single-arm ph II study, Tx-naïve (n=25) and cytokine refractory (n=26) mRCC pts received the same SU Tx. In the ph III study, progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method, with median values compared by log-rank test. In both studies, objective response rate (ORR) was calculated with a two-sided 95% CI. PFS, OS, ORR, and safety were analyzed at final data cutoff. Results: In the ph III study, 31 (8%) and 42 (11%) pts in the SU and IFN groups, respectively, had lung mets only, compared with 12 (24%) in the ph II study. Baseline characteristics in lung mets pts were similar to all pts. In lung mets pts from the ph III study, ORR was higher with SU than with IFN (58.1% [95% CI: 39.1–75.5] vs. 19.0% [95% CI: 8.6–34.1]; P<0.001); there was a trend for longer median PFS with SU (14.1 vs. 7.8 months; HR: 0.531 [95% CI: 0.278–1.015]; P=0.0513); and median OS was comparable in both Tx subgroups (HR: 0.739 [95% CI: 0.335–1.628]; P=0.4507), although, at 25% of events, median OS was 22.9 months with SU vs. 15.8 months with IFN. In lung mets pts from the ph II study, ORR was 75.0% (95% CI: 42.8–94.5); at the time of analysis, median PFS and OS had not been reached; 4 pts (33%) had died due to any cause and 8 (67%) were alive without disease progression. The most common grade ≥3 SU-related AEs were fatigue, hand-foot syndrome, and diarrhea (all 19%) in the ph III study, and decreased platelets (100%), white blood cells (92%), and neutrophils (92%) in the ph II study. Conclusions: In the ph III study, Tx-naïve mRCC pts with lung mets only had significantly higher ORR and a trend for improved PFS and OS with SU compared with IFN. In the Japanese ph II study, ORR with SU was 75% in lung mets pts. Thus, 1st-line use of SU in mRCC pts with lung mets should be encouraged.

A phase 2 trial of lenvatinib 18 mg versus 14 mg once daily (QD) in combination with everolimus (5 mg QD) in renal cell carcinoma (RCC) after 1 prior VEGF-targeted treatment.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS707-TPS707
Author(s):  
Hilary Glen ◽  
Javier Puente ◽  
Daniel Yick Chin Heng ◽  
Sun Young Rha ◽  
Di Li ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
The United States ◽  
Similar Efficacy ◽  
P Value ◽  
Phase 2 ◽  
Double Blind ◽  
Phase 2 Study ◽  
Grade 3

TPS707 Background: Based on findings from a randomized phase 2 study (Study 205), lenvatinib (LEN) + everolimus (EVE) was approved in the United States and European Union for patients (pts) with advanced RCC following 1 prior anti-angiogenic therapy. In that study, LEN 18 mg QD + EVE 5 mg QD significantly prolonged progression-free survival (PFS) compared with either monotherapy. In the LEN+EVE cohort, grades 3 and 4 treatment-emergent adverse events (TEAEs) occurred in 71% of pts. We report the design of an ongoing, multicenter, randomized, double-blind, phase 2 study (Study 218) to evaluate if a lower LEN starting dosage regimen provides similar efficacy with a better safety profile than LEN 18 mg + EVE 5 mg (NCT03173560). Methods: Eligible pts are aged ≥ 18 years with advanced clear cell RCC, 1 prior anti-VEGF therapy, ≥ 1 measurable target lesion per RECIST 1.1, a KPS score of ≥ 70, and prior nivolumab is allowed. Pts will receive LEN 18 mg or 14 mg QD + EVE 5 mg QD in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The LEN 14-mg dose will be escalated to 18 mg if no intolerable grade 2, or any grade ≥ 3 TEAEs requiring dose reduction occur in cycle 1. The primary endpoints are objective response rate (ORR) at week 24 (ORR24W) and the proportion of pts with intolerable grade 2 and any grade ≥ 3 TEAEs within 24 wks after randomization. Secondary endpoints include PFS and ORR. An estimated 306 pts will be randomized. Sample size is based on detecting noninferiority (NI) of ORR24W and superiority of the primary safety endpoint. Two interim analyses (IA) will be performed when 150 and 200 pts have completed 24 wks of follow-up or discontinue earlier. Each analysis will test NI and futility of the LEN 14-mg arm ORR24W vs the 18-mg arm ORR24W. An O’Brien-Fleming boundary will be used for NI. If the 1-sided P-value is ≤ 0.005 at the first IA, ≤ 0.014 at the second IA, or ≤ 0.045 at the final analysis, then NI in ORR24W will be claimed. If the futility boundary is crossed (ie, 1-sided P-value is ≥ 0.776 at the first IA or ≥ 0.207 at the second IA), then futility will be claimed. Clinical trial information: NCT03173560.

Evaluation of patupilone as monotherapy in patients with advanced hepatocellular carcinoma (HCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15055-15055 ◽  
Author(s):  
A. P. Venook ◽  
R. Poon ◽  
Y. K. Kang ◽  
T. S. Mok ◽  
Y. Chao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Objective Response ◽  
Study Drug ◽  
Progression Free Survival ◽  
Hepatic Function ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Vein Thrombosis ◽  
Grade 3 ◽  
Stage 1

15055 Background: Currently, there is no strong evidence that systemic therapies provide a survival benefit for patients (pts) with hCC. However, preclinical data have shown that the novel epothilone patupilone has potent anti-proliferative activity against 8 HCC cell lines with intrinsic multidrug resistance. This exploratory study tested whether patupilone monotherapy has antitumor activity in HCC patients with intact liver function. Methods: This open-label, single-arm, multicenter, 2-stage phase II study was to enroll 24 pts in the first stage and 41 pts in the second stage, if = 3 complete or partial responses were observed in the first stage. Patients with unresectable and/or metastatic HCC (histologically confirmed) with = 1 measurable lesion were eligible if they had well-preserved hepatic function (Child-Pugh Class A) and life expectancy = 3 months. Patupilone was administered as a single IV infusion at 10 mg/m2 over 20 minutes every 3 weeks. Primary endpoint was objective response. Results: Twenty-five patients were enrolled, 24 were evaluable, and 1 violated protocol. The most common adverse events (AEs) suspected to be study-drug related were NCI CTC grade 1/2 diarrhea, fatigue, and vomiting. Grade 4 serious AEs included hyponatremia (2 pts [8%]), cardiac arrest (1 pt [4%]), diarrhea (1 pt [4%]), and gastrointestinal hemorrhage (1 pt [4%]). Grade 3 serious AEs included diarrhea (3 pts [12%]), hyponatremia (2 pts [8%]), deep vein thrombosis (1 pt [4%]), abdominal pain (1 pt [4%]), and hyperkalemia (1 pt [4%]). Most pts had dose adjustments or delays; 3 discontinued treatment. During the first stage, 1 pt had a confirmed partial response through 4 cycles, and 11 pts (44%) had stable disease for = 2 cycles with a median of 4 cycles (range, 2 to 8 cycles). Median progression-free survival was 3 months (range, 1 to 6 months), and 10 pts (40%) progressed within the first 2 cycles. The study did not progress to stage 2. Conclusions: Patupilone demonstrated an acceptable safety profile. Serious AEs were observed in a minority of patients, and most did not require treatment discontinuation. Patupilone demonstrated only modest antitumor activity in pts with HCC in this study. No significant financial relationships to disclose.

The efficacy and safety of CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy in patients with metastatic colorectal cancer: A multi-center, single-arm, phase II study (CCOG-0902 study).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 795-795
Author(s):  
Yuuki Sunakawa ◽  
Goro Nakayama ◽  
Kiyoshi Ishigure ◽  
Hiroyuki Yokoyama ◽  
Keisuke Uehara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Stop And Go ◽  
Grade 3

795 Background: The aim of this study was to evaluate the efficacy and safety of CapeOX plus bevacizumab with a planned oxaliplatin stop-and-go strategy in Japanese patients with metastatic colorectal cancer (mCRC). Methods: Patients with untreated mCRC were treated with 4 cycles of CapeOX plus bevacizumab therapy, followed by capecitabine plus bevacizumab maintenance therapy. Reintroduction of oxaliplatin was scheduled after 8 cycles of maintenance therapy or upon tumor progression. The primary endpoint was progression-free survival (PFS), and secondary end points included overall survival (OS), objective response rate to each treatment, reintroduction rate of oxaliplatin, frequency of peripheral sensory neuropathy (PSN), and safety. Results: The 52 patients who received the protocol treatment were included in the evaluation of efficacy and safety. Median PFS and OS were 12.4 months (95% confidence interval [CI], 10.0–14.8) and 30.6 months (95% CI, 27.6–33.5), respectively. The objective response rates were 55.8% for the initial CapeOX plus bevacizumab therapy, 17.8% for capecitabine plus bevacizumab maintenance therapy, and 31.0% for reintroduced CapeOX plus bevacizumab therapy. The frequency of PSN was 63.5%, including 3.8% of patients with grade 3 PSN. No patients required treatment discontinuation because of PSN during the induction or maintenance therapy. Conclusions: CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy is a feasible first-line treatment for Japanese patients with mCRC. Clinical trial information: UMIN000006478.

A phase ib trial of assessing the safety and preliminary efficacy of a combination therapy of geptanolimab (GB 226) plus fruquintinib in patients with metastatic colorectal cancer (mCRC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15551-e15551
Author(s):  
Yuxian Bai ◽  
Nong Xu ◽  
Shan An ◽  
Wenhui Chen ◽  
Chao Gao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Combination Therapy ◽  
Metastatic Colorectal Cancer ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Once Daily ◽  
Phase Ib ◽  
Grade 3

e15551 Background: A combination of anti-vascular endothelial growth factor receptor(anti-VEGFR) and anti-programmed cell death-1/ligand 1 (PD-1/L1) may synergize with each other and lead to better anti-tumor efficacy. We aimed to assess the safety and preliminary efficacy of combination therapy with geptanolimab (GB226, a highly selective, fully human monoclonal antibody PD-1 mAb) plus fruquintinib (a VEGFR inhibitor) in previously treated metastatic colorectal cancer (mCRC) patients. Methods: In this phase Ib trial, we enrolled mCRC patients who had failed one or two standard therapies. Patients were given geptanolimab (3mg/kg every 2 weeks) and fruquintinib (once daily for 21 days on/7 days off with planned dose cohorts of 3mg, 4mg, and 5mg) on a 28-day cycle. A standard 3+3 design was employed to determine the primary endpoints of the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) based on dose-limiting toxicities (DLT). Secondary endpoints included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Results: By December 15, 2020, 15 patients were enrolled: 1 with MSI-H, 12 with MSS, and 2 with MS unknown. Ten out of 15 patients (66.7%) had received ≥2 previous lines of treatment including chemotherapy in combination with anti-EGFR (33.3%) or anti-VEGF (53.3%). Seven patients (46.7%) were found to have the PD-L1 combined positive score (CPS)≥1. Two DLTs (one patient with grade 3 ALT and AST elevation and one patient with grade 3 proteinuria) were identified in fruqintinib 5mg cohort (6 patients enrolled). No DLT was observed in either 3mg (3 patients enrolled) or 4mg (6 patients enrolled) cohorts. RP2D of this combination was identified as geptanolimab (3mg/kg, every 2 weeks) and fruquintinib (4mg, once daily for 21 days on/7 days off). In all evaluable patients, the overall ORR was 26.7% (4/15, 3 confirmed PR, 1 unconfirmed PR), and the ORR was 33.3% (2/6) in the RP2D group. The DCR for all evaluable patients was 80%, and the median PFS (mPFS) was 7.33 months (95% CI: 1.91 – NE). The median DOR and median OS was not reached at the data cut-off date. Among 12 patients with MSS, the ORR was 25.0% (3/12, 2 confirmed PR, 1 unconfirmed PR), DCR was 75% and mPFS was 5.45 months (95% CI: 1.84-9.66). All patients had at least 1 treatment related AE (TRAE). The common TRAE were proteinuria (46.7%), hypertension (46.7%), and elevated aspartate aminotransferase (40.0%). Grade 3 AEs were observed in 46.7% of patients and the most common grade 3 AE was hypertension (20.0%). No grade 4 and 5 TRAE was observed. Conclusions: The combination of geptanolimab and fruquintinib had manageable safety profiles and encouraging anti-tumor activity in mCRC patients. Clinical trial information: NCT03977090.

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