Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP) following first-line sorafenib: Pooled efficacy and safety in Japanese patients across two global randomized phase III studies (REACH-2 and REACH).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 320-320 ◽  
Author(s):  
Masatoshi Kudo ◽  
Takuji Okusaka ◽  
Kenta Motomura ◽  
Izumi Ohno ◽  
Manabu Morimoto ◽  
...  
Keyword(s):  
Japanese Patients ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
Double Blind ◽  
Study Results ◽  
Phase Iii Studies

320 Background: Ramucirumab (RAM), a human IgG1 monoclonal antibody, inhibits ligand activation of VEGFR2. REACH and REACH-2 were two global, randomized, double-blind, placebo (PBO)-controlled multicenter, phase III studies of RAM versus PBO in patients with HCC after prior sorafenib. REACH-2 confirmed RAM treatment benefit for patients with baseline AFP ≥ 400 ng/mL, consistent with results in a prespecified subgroup of patients in REACH with AFP ≥ 400 ng/mL. Methods: Other than AFP levels, study designs and eligibility for both studies were similar. All patients received RAM (8 mg/kg) I.V. or PBO every 14 days. Pooled analyses were performed to further support the assessments of efficacy and safety in Japanese patients with baseline AFP ≥ 400 ng/mL. Results: In total, 101 Japanese patients were pooled from REACH and REACH-2 (n = 61 RAM; n = 40 PBO). Pooled baseline patient characteristics were balanced between arms including baseline AFP and etiology. As in the individual studies, improvement in OS (median OS 10.78 vs 4.47 mo; HR 0.555; 95% CI 0.348, 0.885; p = .0124) was observed. Improvements in PFS (median PFS 3.88 vs 1.41 mo; HR 0.341; 95% CI 0.212, 0.550; p < .0001), ORR (9.8% vs 2.5%, p = .1285), and disease control rate (67.2% vs 35.0%, p = .0035) were also observed. Consistent with individual study results, hypertension was the only grade 3 or higher adverse events of special interest among ≥ 5% patients that was more frequently observed in the RAM arm (13.1%) compared with the PBO arm (5.0%). Conclusions: Pooled analysis of two phase III trials of RAM as second-line treatment in patients with HCC following first-line sorafenib demonstrated a clinically meaningful benefit with a manageable safety profile in Japanese HCC patients with baseline AFP ≥ 400 ng/mL. Treatment benefits in OS observed in the Japanese subpopulation were consistent with the entire population (median OS 8.1 vs 5.0 mo; HR 0.694; p = .0002. Zhu AX et al., World GI 2018). Further analysis to characterize the Japanese patients compared to the non-Japanese population is planned. Clinical trial information: NCT01140347 (REACH), NCT02435433 (REACH-2).

Nonstandard first-line therapy and survival in patients (pts) with recurrent/metastatic head and neck cancer (RMHNSCC): Experience of 194 pts in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16036-e16036
Author(s):  
Jerome Fayette ◽  
Valentine Polivka ◽  
Sylvie Chabaud ◽  
Bertrand Favier ◽  
Severine Racadot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Alternative Therapy ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Phase Iii Studies ◽  
Line Chemotherapy

e16036 Background: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Methods: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Results: At initiation of palliative chemotherapy, median age was 62 [29-87]; PS was 0, 1, 2, 3 in 13%, 59%, 16% and 11% of pts, respectively. First line chemotherapy consists in combination cisplatin+taxanes (CIST) 24%, caboplatin+taxanes (CART) 33%, cisplatin or carboplatin without taxanes (NOT) 15% or others (OTH) 28%. Median OS was estimated to 9.6 months CI95%=[8.1-11.4], with 39% of pts; CI95%=[32-47] still alive at 1-year. Second line of treatment has been initiated in 61% of pts. Some of them have even been able to have up to 3, 4 or more than 4 lines of treatment in 19%, 11% and 4% of pts, respectively. In the subgroup analysis, which represents a population similar to those included in [ref1], first line chemotherapy was CIST, CART, NOT or OTH in 30%, 30%, 18% and 22%, respectively. Median OS was 13.0 months, CI95%=[11.2-17.7] reaching up to 15.3 months for CIST subgroup. Second line of treatment was initiated in 73% of pts, with 20%, 15% and 5% of pts having a third, a fourth, and a fifth line, respectively. Conclusions: We can reach for unselected pts the best OS published in phase III studies. The use in first line of combination of platinum and taxanes, followed by monotherapies with cetuximab, capecitabine and methotrexate allows reaching OS of 13 months.

Efficacy and safety of paclitaxel/ramucirumab as the second-line chemotherapy in Japanese patients with advanced gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15540-e15540
Author(s):  
Tetsuya Kusumoto ◽  
Akinori Egashira ◽  
Hideto Sonoda ◽  
Kenkichi Hashimoto ◽  
Hideo Uehara ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Japanese Patients ◽  
Phase Iii ◽  
Weekly Dose ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

e15540 Background: Second-line chemotherapy can now be considered as a proven treatment option for metastatic or locally advanced gastric cancer (AGC). Two global randomized phase III trials (REGARD and RAINBOW) showed that survival benefit was significantly observed in patients treated with ramucirumab (RAM) alone and in combination with weekly doses of PTX, compared with placebo, respectively. The purpose of the study is to evaluate the efficacy and safety of weekly dose of PTX combined with RAM practically as the second-line treatment in Japanese patients with AGC refractory to an S-1-containing chemotherapy regimen. Methods: We conducted a retrospective review of the data of 18 patients with AGC who received more than 2 cycles of PTX/RAM combined chemotherapy as the second-line regimen following S-1-based treatment. The objective response rate (ORR), adverse events, progression-free survival (PFS) and overall survival (OS) were analyzed and compared with PTX monotherapy group. Results: Median number of courses were 5 for the PTX/RAM group and the discontinuation of treatment except for disease progression was found in 2 cases (33.3%). The rates of hematological toxicities of higher than grade 3 were 33.3% in the PTX/RAM group, which were higher than those found in the PTX groups. The tumor responses of the PTX/RAM group were 22% for the ORR and 78% for the DCR, compared with 21% and 48% in the PTX group, respectively. The dose intensities of PTX were 72.4% in the former group. The survival data showed that the MST after second-line exposure was 290 days and the median PFS was 131 days in the PTX/RAM group, compared with 159 days and 90 days in the PTX group, which were not significantly different. Conclusions: PTX/RAM might be one of the best regimens for Japanese patients with AGC as the second-line treatment following S-1-containing chemotherapy.

scholarly journals Role of immunotherapy in the management of hepatocellular carcinoma: current standards and future directions

2020 ◽  
Vol 27 (S3) ◽  
Author(s):  
A. Weinmann ◽  
P.R. Galle
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Clinical Trials ◽  
Statistical Significance ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Promising Therapeutic Approach

 The multikinase inhibitor sorafenib was the only approved systemic therapy in advanced hepatocellular carcinoma (hcc) for about a decade. In recent years, the number of approved agents has increased significantly as a result of a number of positive phase iii clinical trials. Lenvatinib as a first-line treatment, and regorafenib, cabozantinib, and ramucirumab in the second-line setting are now approved by the U.S. Food and Drug Administration (fda) and the European Medicines Agency. In phase ii studies, immunotherapy with nivolumab and monotherapy using pembrolizumab yielded impressive results for overall survival in therapy-naïve and pretreated patients, leading to the accelerated approval by the fda of nivolumab and pembrolizumab for second-line treatment. However, phase iii trials of nivolumab in the first line and pembrolizumab in the second line as single agents failed to reach statistical significance, although clinical benefit for a subset of patients with long durations of response could be demonstrated. Despite that setback, immunotherapy for hcc is a promising therapeutic approach, and the combination of immunotherapy with other treatment modal­ities such as monoclonal antibodies, tyrosine kinase inhibitors, or local therapies has the potential to increase the overall response rate and survival. Recently, the results of a phase iii trial of combination atezolizumab–bevacizumab compared with sorafenib showed a highly significant survival benefit and median overall survival that was not reached in the immunotherapy arm, making the combination the preferred standard of care in first-line therapy. Despite the impressive results and generally good toxicity profile of immunotherapy, patients who respond to therapy constitute only a subset of the overall population, and response rates are still limited. This review focuses on the currently reported results and ongoing clinical trials of checkpoint inhibitor–based immunotherapy in hcc.

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