KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 228-228
Author(s):  
Hope Elizabeth Uronis ◽  
Christel Rushing ◽  
Gerard C. Blobe ◽  
Shiaowen David Hsu ◽  
Niharika B. Mettu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
First Line ◽  
Tumor Biopsy ◽  
Gastroesophageal Junction Adenocarcinoma

228 Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination cytotoxic chemotherapy. Single agent P is FDA approved for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GEJ) whose tumors have a combined positive score (CPS) ≥ 1 after disease progression on or after two lines of therapy including fluoropyrimidine and platinum and her2/neu-targeted therapy (if indicated). More effective therapy is needed earlier in the disease trajectory. We conducted a single-arm phase II trial to establish the safety and efficacy of first-line C and O + P. Methods: Pts with previously untreated metastatic GE adenocarcinoma regardless of PDL-1 status received intravenous (IV) P 200mg with IV O 130mg/m2 every three weeks and oral C 850mg/m2 twice daily for 14 days on/7 days off. After the 6 patient safety cohort, pts first completed a biomarker cycle that included fresh tumor biopsy before P and one week after P before chemotherapy started. Archived FFPE tumor samples were also obtained from all pts with available tissue. The primary endpoint was progression free survival (PFS); secondary endpoints included response rate (RR) and overall survival (OS). Results: 36 pts were enrolled and 34 pts were evaluable for efficacy (1 pt withdrew for personal reasons before end of cycle 1 and 1 pt had immune-related toxicity during cycle 1 and was taken off study before any efficacy assessment). 9 pts (26%) had an esophageal primary, 18 pts (53%) had a GEJ primary and 7 pts (21%) had a gastric primary. Median PFS was 7.6 months [95% CI: 5.8 to 12.2], RR was 72.7% [95% CI: 57% to 88%], and median OS was 15.8 months [95% CI: 11.6 to NE]. 27 patients (81.8%) had decrease in disease burden (ranging from -19% to -100%). After > 18 months of follow-up, 5 patients remained in durable complete response (CR). Immune-mediated treatment related adverse events (TRAEs) included thyroid disorders (n=5; 14%), colitis (n=4; 11%), adrenal insufficiency (n=2; 5%), and type 1 diabetes (n=1). Sixteen patients (44%) experienced grade 3 or 4 TRAEs. There were no grade 5 TRAEs. Conclusions: The combination of C and O + P had acceptable safety and significant clinical activity. These promising results indicate that C and O + P merits further study as a first line option for patients with unresectable locally advanced or metastatic GE adenocarcinoma. Updated survival and correlative data will be presented. Clinical trial information: NCT03342937.

EVERSUN: A phase II trial of everolimus alternating with sunitinib as first-line therapy for advanced renal cell carcinoma (RCC) (ANZUP trial 0901).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4681-TPS4681 ◽  
Author(s):  
Ian D. Davis ◽  
Val Gebski ◽  
Mark D. Chatfield ◽  
Peter S. Grimison ◽  
George Kannourakis ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Prognostic Score ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

TPS4681 Background: Treatment of RCC has improved due to better understanding of its biology. New targeted therapies have improved time to progression and overall survival but the optimal sequencing of agents is unknown. Currently drugs are given sequentially, usually starting with sunitinib and often followed by an mTOR inhibitor or another VEGFR-targeted therapy, but resistance to both drugs eventually occurs probably due to host adaptive responses. We hypothesize that resistance might be delayed by planned alternation of treatments. Methods: EVERSUN is a single-arm, two-stage, multicenter, phase II clinical trial aiming to determine the activity and safety of an alternating regimen of two therapies with different targets (sunitinib and everolimus) in patients with advanced RCC. Key eligibility criteria: RCC with a clear cell component; metastatic or locally advanced disease not suitable for resection; ECOG performance status 0-1; low or intermediate MSKCC prognostic score. The primary endpoint is the status of being alive and progression-free (RECIST 1.1) 6 months after registration. Target accrual of 55 subjects gives 95% power and 95% confidence to distinguish between 6-month progression free survival rates of 64% or lower vs 84% or higher using a Simon 2-stage minimax design. The criteria for further evaluation come from the pivotal trial of single agent sunitinib as first line therapy for RCC, in which the 6-month progression free survival rate was 74%. Trial treatment is administered in 12-week (wk) cycles consisting of 4 wks of sunitinib (50 mg daily) followed by 2 wks rest, followed by 5 wks of everolimus (10 mg daily) followed by 1 wk rest. Disease progression is interpreted as failure of the most recent drug taken. Participants who stop one drug because of toxicity or disease progression, on or before the 6 month assessment, will continue the other drug until subsequent progression or prohibitive toxicity on the second drug. EVERSUN is an ANZUP Cancer Trials Group Ltd. trial coordinated by the NHMRC Clinical Trials Centre. Accrual commenced in September 2010 with 38/55 participants recruited as of the 31-Jan-12 from 17 Australian sites (ACTRN12609000643279).

scholarly journals Induction Chemotherapy Followed by Concurrent Chemo-Radiotherapy for Locally Advanced Gastro-Esophageal and Gastric Carcinoma

2021 ◽  
pp. 35-44
Author(s):  
Nora Shaband ◽  
Niveen Abo-Touk ◽  
Mohamed Elawadi ◽  
Saleh Ta-Ema
Keyword(s):  
Induction Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Esophageal Stenosis ◽  
University Hospital ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Gastroesophageal Adenocarcinoma

Aims: To assess the safety and efficacy of chemo-radiotherapy before radical surgery in locally advanced gastric and gastroesophageal adenocarcinoma. Study Design: This was a prospective phase Ⅱ single arm study. Place and Duration of Study: Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital, Mansoura, Egypt, between May 2017 and June 2019. Methodology: Patients with pathologically proven gastric or gastroesophageal junction adenocarcinoma are included. They received one cycle of induction chemotherapy paclitaxel-carboplatin, [paclitaxel dose of 175 mg/m2, carboplatin dose of (AUC: 5)], followed by CCRT [RT 45 Gy over 25 fractions over 5 weeks concurrent with weekly paclitaxel at a dose of 50 mg/m2, carboplatin at a dose of (AUC: 2)], followed by surgery and 2 cycles of paclitaxel-carboplatin for responders. Results: The study included 24 patients. Most of the patients were diagnosed at stage III (83.3%). There were no major side effects of the induction chemotherapy cycle. There were no reported grade 3 or 4 toxicities for the CCRT. Only two patients suffered from late radiation toxicities (distal esophageal stenosis). Pathological complete response was achieved in seven patients (31.8%). Twenty-two patients had surgical resection with a 95% resection margin zero. The median follow-up time was 22.5 months. The median progression-free survival (PFS) and overall survival (OS) were 23, 23.5 months, respectively. Conclusion: The preliminary data suggested good efficacy of the studied treatment design with acceptable adverse-event rates, however a larger multicentric phase 3 trial with a longer follow-up duration is recommended.

Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response observed in adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 41-41 ◽  
Author(s):  
D. Ilson ◽  
Y. Y. Janjigian ◽  
M. A. Shah ◽  
L. H. Tang ◽  
D. P. Kelsen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Node Disease ◽  
Grade 3

41 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial combining sorafenib with chemotherapy in GE cancer (J Clin Oncol 27:2947;2010). We are studying single agent sorafenib in a phase II trial with the primary endpoint to assess progression free survival (PFS). Secondary endpoints include response and therapy tolerance. Methods: Patients (pts) with measurable metastatic E and GEJ cancer with no more than 3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Sixteen of 35 pts have been accrued and 14 are currently evaluable. 13 male, 3 female, median KPS 80%, age 58, GEJ 7, E 9, squamous 2, adenocarcinoma (AC)14. An ongoing complete response (11+ months) was observed in a pt with biopsy proven metastatic neck lymphadenopathy (E primary AC, recurrence after prior chemoradiotherapy and surgery). A second pt (GEJ AC) had protracted stable disease in bulky celiac node disease (15+ months). Grade 3 toxicity was limited to skin rash (1 pt), hand foot reaction (1 pt), and fatigue (1 pt). Only 3 of 14 pts (21%) had early disease progression at 2 months or less. Median PFS 4 mos, 4 patients (29%) continue on therapy for more than 7 months. The majority of tumors tested positive for phospho-erk by immunohistochemistry (11/14, 79%). Conclusions: The observation of a durable complete response and protracted stable disease to sorafenib in E cancer is remarkable. Further accrual continues to define PFS. Supported by a grant from Bayer. [Table: see text]

Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response and prolonged stable disease observed in adenocarcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 91-91
Author(s):  
Geoffrey Y. Ku ◽  
Yelena Yuriy Janjigian ◽  
Manish A. Shah ◽  
Jessica Herrera ◽  
Laura H. Tang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Secondary Endpoints ◽  
Grade 3

91 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial of sorafenib with chemotherapy in GE cancer (J Clin Oncol 27:2947;2010). We performed a phase II trial of single-agent sorafenib with the primary endpoint of progression-free survival (PFS). Secondary endpoints include response and toxicity. Methods: Patients (Pts) with measurable metastatic E and GEJ cancer with ≤3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Thirty-five patients have been accrued, with 34 evaluable; median age 62, 31 male, 4 female, median KPS 80%, E 25, GEJ 10, adenocarcinoma (AC) 30 squamous 5, median no. of prior therapies 2. Of 31 response-evaluable Pts, 1 (3%) ongoing complete response was noted (34+ months) in a Pt with E AC with biopsy-proven lymph node recurrence after chemoradiation and surgery; 23 Pts (74%) had stable disease. Median PFS is 3.7 months (95% CI 1.9 to 4 months), with median overall survival 8.9 months (95% CI 6.9 to 11.6 months). Four patients remain on treatment. Significant grade 3 toxicities included hand foot reaction (3 Pts), rash (1 Pt), dehydration (3 Pts) and fatigue (2 Pts). Twenty-seven of 33 tumors (82%) tested positive for phospho-ERK by immunohistochemistry. Conclusions: Encouraging activity in terms of PFS has been noted in this heavily pre-treated population. Updated data will be presented. Supported by a grant from Bayer. Clinical trial information: NCT00917462.

Safety, PD-L1 expression, and clinical activity of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with advanced gastric or gastroesophageal junction cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 167-167 ◽  
Author(s):  
Hyun Cheol Chung ◽  
Hendrik-Tobias Arkenau ◽  
Lucjan Wyrwicz ◽  
Do-Youn Oh ◽  
Keun-Wook Lee ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Clinical Activity ◽  
Prior Therapy ◽  
Gastroesophageal Junction Cancer ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Disease Stabilization ◽  
Phase Iii Trials

167 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. We report safety and clinical activity of avelumab in patients (pts) with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) based on level of PD-L1 expression. This phase Ib JAVELIN study (NCT01772004) enrolled pts who had progressed on prior therapy ( ≥ 2L) and pts who had received 1L chemotherapy but had not yet progressed (switch-maintenance [Mn]) Methods: Pts received avelumab 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumours were assessed every 6 wks (RECIST 1.1). Best overall response and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry using various cutoff criteria Results: As of Feb 13, 2015, 75 pts with GC/GEJ were treated with avelumab (20 pts, 2L; 55 pts, Mn). Treatment-related treatment-emergent AEs (TR-TEAEs) of any grade occurred in 47 pts (62.7%); the most common ( > 10%) was infusion-related reaction (12 [16.0%], all grade 1/2). Nine pts (12.0%) reported a grade ≥ 3 TR-TEAE, including fatigue (2), thrombocytopenia (2), and anemia (2; each 2.7%). There was 1 treatment-related death (hepatic failure/autoimmune hepatitis). Responses were observed in 7 pts (3/20 2L, all PRs; 4/55 Mn, 1 CR, 3 PRs). PD-L1 expression was evaluable in 55 pts (12/20 2L, 43/55 Mn), including in 3 pts with a response. Median PFS in 2L group was 36.0 wks (95% CI: 6.0, 36.0) for PD-L1+ and 11.6 wks (2.1, 21.9) for PD-L1− ( ≥ 1% cutoff). In Mn group, median PFS for PD-L1+ and PD-L1− status was 17.6 wks (5.9, 18.0) and 11.6 wks (5.7, 17.7), respectively ( ≥ 1% cutoff). Conclusions: Single agent avelumab showed an acceptable safety profile and clinical activity in GC/GEJ pts. Objective responses and disease stabilization were observed in both groups. Median PFS was longer in PD-L1+ pts. Phase III trials in 1L and 3L GC/GEJ are underway.*Proposed INN Clinical trial information: NCT01772004.

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 .

Randomized phase II study of PEP02, irinotecan, or docetaxel as a second-line therapy in gastric or gastroesophageal junction adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 6-6 ◽  
Author(s):  
D. Cunningham ◽  
S. Park ◽  
Y. Kang ◽  
Y. Chao ◽  
L. Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Tumor Response ◽  
Phase Ii Study ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Randomized Phase Ii ◽  
Grade 3

6 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan (CPT-11). In phase I studies, PEP02 has improved pharmacokinetics (PK) of CPT-11 and its active metabolite-SN38 with encouraging safety and tumor response in several cancer types including gastric cancer. This study evaluated the efficacy and safety of PEP02 (P), irinotecan (I) or docetaxel (D) as a single agent in gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods: A randomized, 3 arms (1:1:1), Simon's 2-stage (2/21, 5/41 based on tumor response) study was conducted in Europe and Asia. Patients (pts) with locally advanced or metastatic disease, failed to one prior chemotherapy, ECOG PS ≤ 2, at least 1 measurable lesion, no prior CPT-11 or taxane, were treated with P - 120 mg/m2, I - 300 mg/m2, or D - 75 mg/m2 every 3 weeks. PK and pharmacogenetics (PGx) samples were collected for pts in P and I arms. Results: A total of 135 pts were randomized with 132 (44 per arm) treated between Jan 2008 and Jun 2010. Pts demographics (P/I/D): median age: 56/62/58, male (%): 79.5/77.3/77.3, Pts from Europe (%): 54.6/52.3/56.8, metastatic (%): 97.7/90.9/97.7, gastric adenocarcinoma (%): 84.1/79.6/68.2, and ECOG 0 + 1 (%): 93.2/93.2/90.9. The confirmed responders of P/I/D were 6 (13.6%)/3 (6.8%)/7 (15.9%) and disease control were 27 (61.4%)/27 (61.4%)/24 (54.6%). These three arms have similar progression free survival and overall survival. If stratified by region, Asian pts had longer survival than European pts. Toxicities of P/I/D were: grade 3/4 neutropenia (%): 9.1/13.6/15.9. grade 3/4 diarrhea (%): 27.3/18.2/2.3, hand-foot syndromes (%): 0.0/6.8/18.2. It was notable that symptoms related to acute cholinergic syndrome were less reported in P arm than in I arm. The PK data showed the mean T1/2, Cmax and AUC0→∞ of SN-38 in P/I arms were 88.8/22.8 hr, 8.79/44.1 ng/mL and 879/440 hr x ng/mL. Conclusions: This randomized phase II study suggests that PEP02 improves the PK profile and tumor response over irinotecan, and it is as efficacious as docetaxel in the 2nd-line treatment for gastric or GEJ adenocarcinoma. PEP02 is worthy of further evaluation as either 1st- or 2nd-line setting in future gastric cancer studies. [Table: see text]

Comparison of efficacy and tolerance of first-line palliative chemotherapy EOX and mDCF regimens in patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 135-135 ◽  
Author(s):  
Sebastian Ochenduszko ◽  
Kamil Konopka ◽  
Miroslawa Puskulluoglu ◽  
Katarzyna Urbanczyk ◽  
Andrzej Budzynski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Palliative Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Grade 3

135 Background: The aim of the study was to compare efficacy and tolerance of first-line palliative chemotherapy EOX (epirubicin/oxaliplatin/capecitabine) and mDCF (docetaxel/cisplatin/5FU/leucovorin) regimens in patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors. Methods: Each chemotherapy regimen was assigned with 21 patients. Planned treatment consisted of 12 every-two-weeks mDCF cycles (docetaxel 40 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1, 5FU 1000 mg/m2/d days 1 and 2, cisplatin 40 mg/m2 day 3) or 8 every-three-weeks EOX cycles (epirubicin 50mg/m2 day 1, oxaliplatin 130mg/m2 day 1, capecitabine 1250mg/m2/d days 1 to 21). The primary endpoint was overall survival in all patients who commenced at least one chemotherapy cycle. Results: Median progression-free survival was 5.8 months in EOX group and 7.5 months in mDCF group (p=0.11), and median overall survival was 8.5 months and 12.0 months respectively (p=0.219). Due to toxicity, patients in the EOX arm had more frequent reductions of cytostatics doses (42.9% vs 5.0%; p=0.009) as well as delays in the administration of subsequent chemotherapy cycles (81.0% vs 65.0%; p=0.424). Rates of all grade 3 or 4 adverse events were comparable between both arms (76.19% in the EOX vs 70.0% in the mDCF; p=1.000). Toxicities that occurred more frequently in the EOX group compared to mDCF group were: nausea (28.6% vs 5.0%; p=0.093), thromboembolic events (19.0% vs 10%; p=0.663) and grade 3 or 4 neutropenia (71.4% vs 55.0%; p=0.443). Conclusions: In this patients population with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors treatment with mDCF regimen was associated with a statistically non-significant 3.5 month longer median overall survival without increase in toxicity. Updated data will be presented.

A phase II trial of first-line FOLFIRINOX for patients with advanced gastroesophageal adenocarcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 89-89 ◽  
Author(s):  
Haeseong Park ◽  
Andrea Wang-Gillam ◽  
Rama Suresh ◽  
Caron E. Rigden ◽  
Manik A. Amin ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Therapeutic Option ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
First Line ◽  
Gastroesophageal Adenocarcinoma

89 Background: Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have an approximate 40% objective response rate (ORR). FOLFIRINOX has been used in first line therapy in other GI cancers (i.e pancreatic and CRC) with impressive efficacy signals. Methods: This is a phase II study of first line combination chemotherapy with fluorouracil (5-FU), irinotecan, and oxaliplatin in patients with advanced gastric, esophageal, or gastroesophageal junction adenocarcinoma (NCT01928290). Starting doses were 5-FU 400mg/m2 bolus followed by 2400 mg/m2 over 46 hours with leucovorin 400 mg/m2, irinotecan 180 mg/m2, and oxaliplatin 85 mg/m2. Trastuzumab was administered as 6 mg/kg loading dose then 4 mg/kg every 14 days if patients had HER2+ cancer. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS), overall survival (OS), time to progression (TTP), clinical benefit rate (CBR), and duration of response. Enrollment of 41 patients with HER2- disease was planned to reach one-sided = 0.10 and power 0.90 with goal of detecting true ORR60%. No enrollment goal was planned for HER2+. Results: From Nov 2013 to July 2017, 58 patients were enrolled, 25 out of 58 (43%) had HER2+ disease. Forty-nine patients were evaluable for response as they completed at least one restaging scan. ORR was 78% (38/49) in all patients, 67% (18/27) in HER2-, 91% (20/22) in HER2+. One patient (2%) had complete response, 37 (76%) had partial response, 7 (14%) had stable disease > 6 months; therefore, CBR was 92%. Median PFS is 11.9 months, median OS is 17.4 months and median follow up time 16.1 months. 41 (83.7%) had dose modification or delay during treatment. There were no unexpected toxicities. Conclusions: FOLFIRINOX with or without trastuzumab showed remarkable ORR and PFS in patients with advanced gastroesophageal adenocarcinoma in the first-line setting. This regimen may be a reasonable therapeutic option for patients with preserved performance status. Further investigation in larger population is warranted. Clinical trial information: NCT01928290.

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