First-line pembrolizumab, trastuzumab, and chemotherapy in advanced HER2-positive gastric cancer with sequential genomic profiling

2021 ◽  
Author(s):  
Hyun Cheol Chung ◽  
Choong-kun Lee ◽  
Sun Young Rha ◽  
Hyo Song Kim ◽  
Minkyu Jung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tumor Burden ◽  
First Line ◽  
Her2 Positive ◽  
Genomic Changes ◽  
Barr Virus ◽  
First Line Therapy

Abstract Combining programmed cell death 1 (PD-1) and human epidermal receptor 2 (HER2) targeting agents has shown synergy in HER2-positive preclinical cancer models. Here, we describe a single-arm multi-institutional phase Ib/II trial combining pembrolizumab, trastuzumab, and chemotherapy (capecitabine plus cisplatin) as first-line therapy for HER2-positive advanced gastric cancer (AGC). With a median follow-up of 18.2 months, 3 out of 43 enrolled patients remained in the treatment and 7 finished 2-year treatment without progression. Objective response rate was 76.7% (complete response 16.3%, partial response 60.5%, conversion surgery 4.6%), with 26 patients (56.6%) showing tumor reduction of more than 50%. Median progression-free survival was 8.6 months (95% confidence interval [CI] 7.2–16.4) and median overall survival was 19.3 months (95% CI 16.5–not reached). There was no patient with microsatellite instability-high or Epstein–Barr virus-positive tumor. No patient discontinued pembrolizumab because of immune-related adverse events. Programmed death ligand-1 (PD-L1) status, metastatic organ, or baseline tumor burden were not related to survival. Molecular analyses of pre-treatment tumor samples using next-generation panel sequencing (NGS) showed that HER2 amplification, RTK/RAS pathway alteration, and neoantigen load corrected by HLA-B were related to survival. Comparison analyses of sequentially biopsied samples identified sensitive and resistant sub-clones with spatial and longitudinal tumor heterogeneity. This study provided insight into potentially relevant NGS-based genomic changes to identify patients who may benefit from quadruplet regimen (pembrolizumab, trastuzumab, capecitabine, and cisplatin), which was active and safe for HER2-positive AGC.

scholarly journals The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Hye Ryeon Kim ◽  
Soomin Ahn ◽  
Hyunji Jo ◽  
Hongsik Kim ◽  
Joohyun Hong ◽  
...  
Keyword(s):  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Complete Response ◽  
First Line ◽  
Her2 Positive ◽  
First Line Therapy ◽  
The Status ◽  
Tumor Mutational Burden ◽  
The Impact

BackgroundTrastuzumab is a HER2-trargeted humanized monoclonal antibody that has been studied as a first-line treatment for patients with HER2-positive advanced gastric cancer (AGC). The effect of anti-HER2 therapy according to tumor mutational burden (TMB) in HER2-positive AGC remains unclear.MethodsWe performed next-generation sequencing (NGS), including TMB analysis, in 31 HER2-positive AGC patients with trastuzumab plus chemotherapy as first-line therapy for recurrent (n=8) or metastatic (n=23) tumors. The TruSight Oncology 500 Assay from Illumina (San Diego, CA, USA) was used to evaluate TMB.ResultsAmong 31 patients, 30 had tumors with immunohistochemistry (IHC) 3+, and one was IHC 2+ and silver in situ hybridization (SISH) positive. The median age was 57.0 years old (range, 35-76), and the majority had tumors with low TMB (87.1%, n=27/31). Only four (12.9%) had tumors with high TMB. Of these four, three achieved complete response (CR) or partial response (PR) to treatment, and the remaining patient was not evaluable for tumor response. Objective response rate (ORR) to trastuzumab plus chemotherapy showed a favorable trend in patients with high TMB (75.0%, n=3/4) compared to patients with low TMB (59.3%, n=16/27) (P=0.546). The median progression-free survival (PFS) was not reached in the TMB-high group but was 8.0 months (95% CI, 7.6-8.5) in the TMB-low group (P=0.019)ConclusionThe status of TMB could be a novel biomarker in predicting the efficacy of trastuzumab plus chemotherapy in HER2-positive AGCs.

Efficacy and toxicities of gemcitabine and cisplatin combination chemotherapy in advanced thymoma and thymic carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20007-e20007
Author(s):  
Jian Fang ◽  
Yang Wang
Keyword(s):  
Partial Response ◽  
Combination Chemotherapy ◽  
Thymic Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Gemcitabine And Cisplatin

e20007 Background: Thymoma and thymic carcinoma are rare thymic epithelial tumours. This study investigated the efficacy of first-line gemcitabine and cisplatin combination chemotherapy in advanced thymoma and thymic carcinoma Methods: Retrospective review of patients with histologically-confirmed invasive, metastatic thymoma or thymic carcinoma treated with gemcitabine plus cisplatin as a first-line therapy between August 2008 and February 2016 at the Department of Respiratory Medicine II Peking University Cancer Hospital and Institute. The objective response rate was the primary end point. Results: Forty patients, 13 with thymoma and 27 with thymic carcinoma, were identified. Nine received gemcitabine and cisplatin combined with Endostar (injectable recombinant human Endostatin); 31 received gemcitabine and cisplatin only. Of the 13 patients with thymoma, four (30.8%) achieved a partial response (PR) and nine (69.2%) had stable disease (SD); no patients had a complete response (CR) or progressive disease (PD). Among the 27 patients with thymic carcinoma, 13 (48.1%) achieved a PR, 12 (44.4%) had SD and two (7.4%) had PD; no patients had a CR. In thymic carcinoma, progression free survival (PFS) was 25 months and median survival (OS) was 41 months; in thymoma, median PFS was 29 months and median OS was 77 months. As no patients achieved a complete response, objective response was defined as partial response in this study. Conclusions: This retrospective analysis indicates gemcitabine plus cisplatin has moderate efficacy and could represent a suitable first-line therapy for thymic carcinoma and thymoma, especially for patents who cannot tolerate anthracyclines. [Table: see text]

Final results of a phase II trial of first-line FOLFIRINOX for advanced gastroesophageal cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4532-4532
Author(s):  
Ramon Jin ◽  
Haeseong Park ◽  
Andrea Wang-Gillam ◽  
Rama Suresh ◽  
Caron E. Rigden ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
First Line ◽  
Her2 Positive ◽  
Open Label

4532 Background: Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have moderate clinical benefit with objective response rates (ORR) of approximately 40-50%. FOLFIRINOX has been shown to be an effective and well-tolerated first line therapy in other GI cancers. In this open-label, single-arm phase II study of patients with advanced gastroesophageal adenocarcinomas, we sought to evaluate the safety and clinical activity of FOLFIRINOX. Methods: The primary endpoint was ORR, and secondary endpoints included safety profile, progression free survival (PFS), overall survival (OS), time to progression (TTP), clinical benefit rate (CBR), and duration of response. Estimated sample size included 41 patients with HER2 negative disease with 90% power to detect an ORR≥60% with alpha of 0.10. No enrollment goal was planned for HER2 positive patients, but they were allowed participation to receive study treatment in combination with trastuzumab. Treatment consisted of 400mg/m2 5-FU bolus, 400 mg/m2 leucovorin, 2400 mg/m2 5-FU infusion over 46 hours, 180 mg/m2 irinotecan, and 85 mg/m2 oxaliplatin. Trastuzumab was administered intravenously as a 6 mg/kg loading dose then given 4 mg/kg every 14 days for HER2 positive patients. This trial is registered with ClinicalTrials.gov, NCT01928290. Results: From November 2013 to May 2019, 67 patients were enrolled, of which 26 (39%) had HER2 positive disease. Median follow-up was 16.1 months. ORR was 61% (25/41) for HER2 negative and 85% (22/26) for HER2 positive groups. Overall, one patient (2%) had a complete response, 36 patients (69%) had partial responses, and 13 patients (19%) had stable disease for >6 months; therefore, CBR was 96%. Median PFS was 11.9 months, median OS was 17.4 months. 41 patients (83.7%) had dose modification or treatment delay with the most common toxicities being neutropenia, diarrhea, peripheral sensory neuropathy, and nausea with no unexpected toxicities. Conclusions: FOLFIRINOX is a highly effective three-drug regimen for first-line treatment of advanced gastroesophageal cancer with expected, tolerable toxicities. Clinical trial information: NCT01928290 .

A phase II study of capecitabine plus oxaliplatin (XELOX) as first-line therapy for patients with advanced gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4079-4079 ◽  
Author(s):  
Y. Park ◽  
J. Lee ◽  
B. Ryoo ◽  
M. Ryu ◽  
S. Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Advanced Gastric Cancer ◽  
Combination Chemotherapy ◽  
Progression Free Survival ◽  
Complete Response ◽  
First Line ◽  
First Line Therapy ◽  
Advanced Gastric Carcinoma ◽  
Line Therapy

4079 Background: The combination chemotherapy of capecitabine and cisplatin showed considerable activity and good feasibility in patients with advanced gastric cancer. Oxaliplatin has a more favorable toxicity profile compared to cisplatin. The purpose of the study is to evaluate the efficacy and toxicity of capecitabine plus oxaliplatin combination chemotherapy in previously untreated patients with advanced gastric carcinoma. Methods: Patients received intravenous oxaliplatin 130 mg/m2 over 2 hours on day 1 plus oral capecitabine 1000 mg/m2 twice daily on days 1–14, every 3 weeks. Treatment was continued until progression of disease or intolerable toxicities with a maximum of 8 cycles. All the measurability and response evaluations were reviewed and confirmed by one investigator. Results: Total 54 patients were enrolled (37 men, 17 women). The median age was 57 years (range 29–70). Among these 54 patients, fifty-two patients were evaluable. A total 311 cycles of chemotherapy were delivered. The overall response rate was 63% (95% CI, 50–76%), with complete response in 2 patient and partial responses in 32 patients. After a median follow-up of 13 months, median progression-free survival was 5.8 months (95% CI, 4.4–7.2 months); median overall survival was 11.9 months (95% CI, 8.8–15.1 months). The treatment was generally well tolerated. The most common haematological adverse event was anaemia (70% of patients). Grade 3- 4 neutropenia was observed in 4 patients and neutropenic fever was experienced in only 1 patient. Four patients had G3 thrombocytopenia, which was accompanied by G3 gastrointestinal bleeding. The most common non-haematological toxicities were neuropathy (70%), vomiting (50%), diarrohea (33%), and hand-foot syndrome (39%). But, G3–4 toxicities were rare. There was one treatment related death which was associated with grade IV neutropenic sepsis. Conclusion: XELOX was active and well tolerated as a first-line therapy for advanced gastric carcinoma. No significant financial relationships to disclose.

Combination of mitotane and locoregional treatments in low-volume metastatic adrenocortical carcinoma

2021 ◽  
Author(s):  
Alice Boileve ◽  
Elise Mathy ◽  
Charles Roux ◽  
Matthieu Faron ◽  
Julien Hadoux ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Stage Iv ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tumor Burden ◽  
Interquartile Range ◽  
First Line ◽  
Chemotherapy Administration ◽  
Metastatic Sites

Abstract Purpose European and French guidelines for ENSAT stage IV low tumor burden or indolent adrenocortical carcinoma (ACC) recommend combination of mitotane and locoregional treatments (LRT) in first-line. Nevertheless, the benefit of LRT combination with mitotane has never been evaluated in this selected group of patients. Methods A retrospective chart review was performed from 2003-2018 of patients with stage IV ACC with ≤2 tumoral organs who received mitotane in our center. Primary endpoint was the delay between mitotane initiation and first systemic chemotherapy. Secondary endpoints were progression-free survival (PFS) and overall survival (OS) from mitotane initiation. Adjusted analyses were performed on the main prognostic factors. Results Out of 79 included patients, 48 (61%) patients were female and median age at stage IVA diagnosis was 49.8 years (interquartile-range:38.8-60.0). Metastatic sites were mainly lungs (76%) and liver (48%). Fifty-eight (73%) patients received LRT including adrenal bed radiotherapy (14 patients, 18%), surgery (37 patients, 47%) and/or interventional radiology n(35,44%). Median time between mitotane initiation and first chemotherapy administration was 9 months (Interquartile-range:4-18). Median PFS1 (first tumor-progression) was 6.0 months (CI95%:4.5-8.6). Median OS was 46 months (CI95%:41-68). PFS1, PFS2 and OS were statistically longer in the mitotane plus LRT group compared to the mitotane-only group (Hazard ratio (HR)=0.39 (CI95%:0.22-0.68), HR=0.35 (CI95%:0.20-0.63) and HR=0.27 (CI95%:0.14-0.50) respectively). Ten (13%) patients achieved complete response, all from mitotane plus LRT group. Conclusion Our results endorse European and French guidelines for stage IV ACC with ≤2 tumor-organs and favor the combination of mitotane and LRT as first-line treatment. For the first time, a significant number of complete responses were observed. Prospective studies are expected to confirm these findings.

Efficacy and safety of lenvatinib in the real-world treatment of hepatocellular carcinoma: Results from a Canadian multicenter database (HCC CHORD).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 275-275
Author(s):  
Carla Pires Amaro ◽  
Michael J Allen ◽  
Jennifer J. Knox ◽  
Erica S Tsang ◽  
Howard John Lim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Drug Discontinuation ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
The Real ◽  
First Line Therapy

275 Background: The REFLECT trial establishedlenvatinib (LEN) as a first-line treatment option for hepatocellular carcinoma (HCC). Compared to sorafenib (S), LEN has a higher objective response rate (ORR) and progression-free survival (PFS) with a slightly different toxicity profile. The aim of this study was to gather data regarding the efficacy and safety of LEN when used in the real-world treatment of HCC. To our knowledge, this is the first study to examine LEN use in HCC patients treated outside of Asia. Methods: HCC patients treated with LEN from 10 cancer centers in the Canadian provinces of British Columbia, Alberta, Ontario and Nova Scotia between July 2018 to July 2020 were included. Overall survival (OS), PFS, disease control rate (DCR) and ORR were retrospectively analyzed and compared across first- and second-to-fourth line use of LEN. ORR was determined radiographically according to the treating physician´s opinion in clinical notes and not RECIST 1.1 or mRECIST. Toxicities were also examined. Results: A total of 220 patients were included in this analysis. Median age was 67 years, 80% were men and 25.5% East Asian. The most frequent causes of liver disease were hepatitis C (37%) and B (26%). 62% of patients received any localized treatment before LEN, of those 26% had TACE, 15% TARE and 7.7% had liver transplant. Before starting LEN 29% of patients were ECOG 0 and 59% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (75.5%). Main portal vein invasion was present in 14% of the patients. Median follow-up was 4.5 months. A total of 173 patients (79%) received LEN as first line therapy and 47 patients (21%) were treated in second-to-fourth line. Of patients receiving LEN in first line, 22 (13%) started treatment with S, but switched to LEN before progression due to poor tolerance of S. ORR, DCR, PFS and OS are shown in the table. Toxicities occurred in 86% of patients and led to dose reductions in 76 (35%) patients and drug discontinuation in 53 (24%) patients. The most common side effects were fatigue (59%), hypertension (41%), decreased appetite (25%) and diarrhea (22%). Conclusions: Outcomes of HCC patients treated in Canada with LEN in the first line are comparable to those demonstrated in the REFLECT trial, despite the inclusion of Child-Pugh B and ECOG >1 patients. LEN use in second or later lines also showed similar outcomes, although more conclusions are difficult to draw due to the small numbers. LEN appears to be effective and safe in real world practice outside of Asia in first- and second-to-fourth line treatment of HCC. [Table: see text]

Efficacy of oral vinorelbine (NVBo), capecitabine (X) and trastuzumab (H) triple combination (NVBoXH) in HER2-positive metastatic breast cancer (MBC): First results of an international phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1052-1052 ◽  
Author(s):  
A. Chan ◽  
V. Ganju ◽  
D. Becquart ◽  
P. Conte ◽  
L. Petruzelka ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
First Line ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Oral Vinorelbine

1052 Background: Chemotherapy (CT) plus H is the standard first-line treatment for HER2-positive MBC. H plus vinorelbine is an active and well-tolerated regimen in this setting. The all-oral combination of NVBo and X also appears active and well-tolerated in MBC. We report efficacy and safety results from the first 34 patients (pts) included in an international trial evaluating NVBoXH in HER2-positive MBC. Methods: In this multicenter trial, main eligibility criteria included: HER2-positive disease (IHC 3+ or FISH+), documented measurable MBC previously untreated by CT, relapse 6 months after completing neoadjuvant or adjuvant CT, Karnofsky PS = 70, age =18 years. Pts received 3-weekly cycles of NVBo 60 mg/m2 (cycle 1) escalating to 80 mg/m2 (from cycle 2) days 1 and 8; × 1,000 mg/m2 bid (750 if = 65 years) days 1–14; H 4 mg/kg day 1 as a loading dose then 2 mg/kg i.v. weekly starting on day 8. Treatment was continued until progression or unacceptable toxicity. Primary endpoint is overall response rate. Results: Baseline characteristics: median age 54 years (20% = 65); prior (neo)adjuvant CT 21 pts (62%); type of CT: anthracycline 52%, anthracycline + taxane 29%, CMF 14%, taxane 5%; visceral involvement 29 pts (85%), >2 metastatic sites 13 pts (38%). Treatment administered: median 8 cycles, median relative dose intensity: NVBo 77%, X 81%, H 95%; NVBo dose escalation to 80 mg/m2 in 91% of pts. Safety (n=34, G3/4 NCI CTC v2 adverse events): neutropenia 22 pts (65%), diarrhea 4 pts (12%), febrile neutropenia 3 pts (9%), vomiting 3 pts (9%), hand-foot syndrome 3 pts (9%), asthenia 3 pts (9%), infection without neutropenia 2 pts (6%), LVEF decline 2 pts (6%), stomatitis 1 pt (3%), nausea 1 pt (3%), constipation 1 pt (3%). Efficacy (n=31 evaluable pts): objective response rate (RECIST) 71% (95% CI [52–86]), CR 13%, PR 58%, SD 23%, PD 6%, disease control (CR+PR+ SD for =6 months) 84%. Progression-free survival, overall survival and duration of response data are not yet mature. Conclusions: This is the first trial, in pts with HER2-positive MBC, to show high efficacy with first-line NVBoXH therapy. This regimen can be safely administered in this pt population. No significant financial relationships to disclose.

Retrospective review of modified dose docetaxel, cisplatin, and 5-flourouracil (DCF) for the treatment of first-line metastatic gastric carcinomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15175-e15175
Author(s):  
Nuriye Özdemir ◽  
Sercan Aksoy ◽  
Tulay Eren ◽  
Huseyin Abali ◽  
Omur Berna Oksuzoglu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Retrospective Review ◽  
Progression Free Survival ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
Median Number ◽  
Hematological Toxicity ◽  
First Line ◽  
Gastric Carcinomas ◽  
Grade 3

e15175 Background: Docetaxel, cisplatin, and 5FU (DCF) has been shown to be an effective regimen for metastatic gastric carcinomas. However, treatment-related adverse events is quite high with original dose DCF. We evaluated the outcomes of the metastatic gastric carcinomas who treated with modified dose DCF (mDCF) in our institution. Methods: A single institution retrospective review of patients with metastatic gastric cancer treated with three weekly mDCF from 1/2006 to 1/2013 was evaluated. Over this time period a standard order-set was in place in which cisplatin 60 mg/m2, 5FU 600 mg/m2 and docetaxel 60 mg/m2 was given three weekly. Tumor response was calculated retrospectively using RECIST criteria. Results: One hundred and ninety-one patients were included the study. The median age was 55 years (23 to 76), 74% were male, and 82% were chemo-naive. Eighty percent of the patients were metastatic at the time of diagnosis. The median number of cycles administered was 6 (2-10). Hematological toxicity was mild with grade 3/4 granulocytopenia in 25% of the patients, grade 3/4 thrombocytopenia in 4% of the patients, and grade 3/4 anemia in 9% of the patients. Neutropenic infection occurred in 9 (%5) patients. Grade 3/4 nausea/vomiting was reported by 10% of the patients, and diarrhea by 7%. A total of 19 (10%) patients had dose delays or dose reductions related to toxicity. Six (3%) patients had complete response and 43 (23%) patients had partial response. Stable disease were occurred in 83 (45%) patients and 56 (23%) progressive disease. Ninety percent of the patients have died with median follow-up of 8 months. Progression-free survival was 7 months (95% CI 6 to 7.8 m) and overall survival was 10 months (95% CI 8.7 to 11.2 m). Conclusions: mDCF has mild hematological toxicity and overall excellent tolerance in first line metastatic gastric cancer patients. Response rate and the survival of these patients with a minimal toxicity are comparable with the original dose DCF.

Capecitabine plus bevacizumab (Cape-Bev) as a maintenance treatment after induction treatment with FOLFIRI plus bevacizumab (FOLFIRI-Bev) in metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14683-e14683
Author(s):  
Ali Murat Tatli ◽  
Hasan Senol Coskun ◽  
Mukremin Uysal ◽  
Sema Sezgin Goksu ◽  
Deniz Arslan ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Disease Progression ◽  
Maintenance Treatment ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Induction Treatment ◽  
Severe Toxicity ◽  
First Line

e14683 Background: Bevacizumab is human monoclonal antibody that inhibits vascular endothelial growth factor and has been shown improvement progression-free survival and overall survival when combined with chemotherapy for treatment of mCRC in the first and second-line settings. The purpose of this study is to show the effectiveness of maintenance therapy with Cape-Bev in patients with mCRC who benefit of first-line (induction) chemotherapy with FOLFIRI-Bev. Methods: The study included patients with mCRC who received FOLFIRI-Bev as first-line chemotherapy. Maintenance therapy with Cape-Bev (Cape 1000 mg/m2 bid d1-14, Bev 7,5 mg/kg d1 q3w) was given until disease progression to patients who had achieved an objective response after 6-months FOLFIRI-Bev regimen. The time to disease progression, survival and toxic effects were analyzed from the beginning of bevacizumab-based chemotherapy. Results: We enrolled 30 patients, 16 men and 14 women. The mean age of the patients was 62 years. The patients who administered maintenance treatment received a median number of 11 cycles. The median progression-free and overall survivals were 22±4 months and 39±4 months, respectively. Significantly higher PFS and OS were seen among patients who complete or near-complete response to induction therapy with FOLFIRI-Bev (Table). Acceptable hand-foot syndrome was observed 14 patients (%51) treated with the Cape-Bev. No patient experienced severe toxicity. Conclusions: Cape-Bev regimen may be an effective maintenance treatment after response to first-line (induction) FOLFIRI plus bevacizumab treatment in selected mCRC with favorable safety profile. Further studies will be needed to demonstrate conclusively that. [Table: see text]

Final analysis of the phase 2 APEC study: Overall survival (OS) data and biomarker subanalyses for first-line FOLFOX or FOLFIRI with cetuximab (cet) once every 2 weeks in patients (pts) with KRAS or RAS (KRAS and NRAS, exons 2-4) wild-type (wt) metastatic colorectal cancer (mCRC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 566-566
Author(s):  
Ann-Lii Cheng ◽  
Gerardo H. Cornelio ◽  
Lin Shen ◽  
Timothy Jay Price ◽  
Tsai-Sheng Yang ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Asia Pacific ◽  
First Line ◽  
Ras Mutation ◽  
Mutation Status ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Status

566 Background: The Asia-Pacific, multicenter, nonrandomized, phase II APEC study previously reported that first-line therapy for pts with KRAS ex 2 wt mCRC consisting of C once every 2 weeks combined with FOLFOX or FOLFIRI achieved efficacy and safety profiles comparable to those reported in analogous pivotal studies involving weekly C. This final analysis presents OS data from the KRAS wt intent-to-treat (ITT) population, as well as subgroup efficacy analyses stratified by BRAF, PIKC3A, and all RAS mutation status. Methods: Eligible pts received C once every 2 weeks (day 1 of each cycle, 500 mg/m2) with FOLFOX or FOLFIRI (investigator’s choice). Study treatment continued until disease progression, dose-limiting toxicity or consent withdrawal. The primary endpoint was best confirmed overall response as assessed by RECIST 1.0; progression-free survival (PFS) and OS were secondary endpoints. In the evaluable populations, the status of BRAF, PIK3CA, and all RAS mutations was assessed retrospectively by pyrosequencing. Results: 42 months after the last patient was enrolled, median OS in the KRAS wt population was 26.8 months (Table). There were no unexpected safety findings. Additional biomarker results—including objective response rate (ORR), PFS, and OS subgroup analyses stratified on BRAF, PIKC3A, and all RAS mutation status—will be presented. Conclusions: The observed median OS of 26.8 months in the KRAS wt population is comparable to that reported in prior pivotal studies involving weekly C plus FOLFOX or FOLFIRI in the first line. These results suggest that C plus FOLFOX or FOLFIRI in a once-every-2-weeks regimen is active and tolerable as first-line therapy in this Asia-Pacific study population and a convenient alternative to weekly administration. Clinical trial information: NCT00778830. [Table: see text]

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