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.

scholarly journals Cisplatin, Fluorouracil in Bolus Injection, and Leucovorin in First-Line Therapy for Advanced Gastric Cancer as an Alternative to Protocols With Infusional Fluorouracil

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Rafael C. Coelho ◽  
Pedro D.P. Abreu ◽  
Mariana R. Monteiro ◽  
Ana Paula Stramosk ◽  
Alvaro Henrique I. Garces ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Progression Free Survival ◽  
Median Number ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Line Setting ◽  
Platinum Agents

PURPOSE Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death worldwide. Platinum agents and fluoropyrimidines are the main compounds used in the first-line setting for advanced GC. Given the activity of fluorouracil (FU) bolus, the PFL protocol, a chemotherapy regimen combining cisplatin, FU bolus, and leucovorin, was incorporated at the Brazilian National Cancer Institute, because this schedule does not require hospitalization or infusion pumps. This study aims to evaluate the outcomes of PFL in the first-line setting for patients with advanced GC. MATERIALS AND METHODS This was a retrospective cohort study evaluating patients with advanced GC treated in the first-line setting with cisplatin 80 mg/m2 on day 1 and FU bolus 400 mg/m2 plus leucovorin 20 mg/m2 on days 1, 8, 15, and 22 every 4 weeks, from January 2008 to December 2014. RESULTS A total of 109 patients were enrolled. The median number of cycles received per patient was four (one to 11). Complete responses were achieved in 6.4% and partial responses in 14.7%. Median progression-free survival was 6.3 months (95% CI, 5.08 to 7.58 months) and median overall survival was 8.3 months (95% CI, 6.79 to 9.87 months). Thirty-four (31.2%) patients were alive in 1 year. Grade 3 and 4 adverse events were experienced by 26.6% and 3.7% of patients, respectively, with dose reduction necessary in 9.1%. CONCLUSION PFL is active in advanced GC and could be an alternative for FU continuous infusion protocols in institutions with limited resources and/or low budget, which is the reality in many nations all over the world.

A phase II study of oxaliplatin with biweekly, low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients with advanced or metastatic gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14052-14052
Author(s):  
H. Kim ◽  
H. Kwon ◽  
S. Y. Oh ◽  
B. G. Seo ◽  
S. G. Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Continuous Infusion ◽  
Low Dose ◽  
Overall Response Rate ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

14052 Background: To determine the activity and toxicities of low dose leucovorin (LV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin every two weeks (modified FOLFOX-4), as a first-line therapy for patients with advanced or recurrent gastric cancer. Methods: Between January 2003 and March 2005, forty-five patients were enrolled in this study. Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion at day 1 plus LV 20 mg/m2 over 10 minutes, followed by 5-FU a 400 mg/m2 bolus and 22 hour continuous infusion of 600 mg/m2 5-FU at day 1–2. This treatment was repeated in 2 week intervals. Results: There was one patient (2.2%) demonstrated a complete response. Twenty patients (44.4%) showed a partial response. Overall response rate was 46.6%. Ten patients (22.2%) showed a stable disease and fourteen patients (31.1%) progressed during the course of the treatment. The median time to progression and overall survival time were 7.73 months (95% CI: 3.6–11.86 months) and 11.17 months (95% CI: 9.06–13.28 months) from the start of the chemotherapy, respectively. A total of 247 cycles were analyzed for toxicity. Major hematologic toxicities included grade 1–2 anemia (39.7%), neutropenia (30.4%), grade 3–4 neutropnenia (10.9%) and thrombocytopenia (9.3%).There were 12 cycles of neutropenic fever. The most common non-hematological toxicities were grade 2 nausea/vomiting (20%), grade 1–2 neuropathy (13.4%) and grade 3 diarrhea (2.2%). There was no treatment related death. Conclusions: The modified FOLFOX-4 regimen is safe and effective regimen as a first line therapy in advanced or metastatic gastric cancer. No significant financial relationships to disclose.

S-1+oxaliplatin with pembrolizumab for advanced gastric cancer: The cohort 1 in a phase IIb KEYNOTE-659 study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 382-382
Author(s):  
Hisateru Yasui ◽  
Akihito Kawazoe ◽  
Kensei Yamaguchi ◽  
Yuji Negoro ◽  
Mizutomo Azuma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Median Number ◽  
First Line ◽  
Ecog Performance Status ◽  
Duration Of Response ◽  
Grade 3

382 Background: The KEYNOTE-059 study showed the preliminary antitumor activity and tolerability of chemotherapy with pembrolizumab (P) for advanced gastric cancer (AGC). In Japan, S-1 + platinum regimen is a standard chemotherapy for AGC. The KEYNOTE-659 study (NCT03382600) investigated the efficacy and safety of S-1 + oxaliplatin (SOX; cohort 1) or cisplatin (SP; cohort 2) with P as the first line treatment in patients (pts) with human epidermal growth factor receptor 2 (HER2)-negative, programmed death-ligand 1 (PD-L1)-positive AGC. Here, we report the results of cohort 1. Methods: The key inclusion criteria were as follows: age ≥18 to ≤75 years; an ECOG performance status of 0 or 1; and chemotherapy-naïve, HER2-negative and PD-L1-positive AGC. PD-L1 positivity was defined as a combined positive score of ≥1 using the IHC 22C3 PharmDx assay. An S-1 dose of 40-60 mg per dose was orally administered, twice daily, for the first 2 weeks of a 3-week cycle. P (200 mg) and oxaliplatin (OX; 130 mg/m2) were administered on day 1 of each cycle. The primary endpoint was overall response rate (ORR) that was assessed by a blinded independent central review (BICR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety. Results: From April to September 2018, 54 pts were enrolled at 25 sites in Japan. The median follow-up time was 10.1 months. The median number of P doses and cycles in SOX were 9 (range, 2-18) and 6 (range, 2-13), respectively. The relative dose intensities of S-1 and OX were 73% and 60%, respectively. The ORR and DCR assessed by BICR were 72.2% (95% CI 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. The median PFS was 9.4 months (95% CI 6.6-NR). Median DOR and OS were not reached. Grade ≥3 adverse events (AEs) were reported in 31 pts (57.4%). The most common treatment-related AEs of grade ≥3 were thrombocytopenia (14.8%), neutropenia (13.0%), colitis (7.4%), and adrenal insufficiency (5.6%). There were no treatment-related deaths. Conclusions: This study showed the encouraging efficacy and manageable safety of SOX with P therapy as a first line in pts with HER2-negative, PD-L1-positive AGC. Clinical trial information: NCT03382600.

scholarly journals Study of Gemcitabine Plus Nab-Paclitaxel-Based Chemotherapy Regimen as First-Line Treatment in Metastatic Pancreatic Carcinoma

2021 ◽  
Author(s):  
Kshitij Domadia ◽  
Varun Goel ◽  
Venkata Pradeep Babu Koyyala ◽  
Nivedita Patnaik ◽  
Krushna Chaudhari ◽  
...  
Keyword(s):  
Pancreatic Carcinoma ◽  
Chemotherapy Regimen ◽  
Objective Response ◽  
Safety Data ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
First Line ◽  
Significant Difference ◽  
Grade 3

Background The purpose of this study was to study the effectiveness of gemcitabine and nab-paclitaxel combination as first-line chemotherapy regimen for the treatment of metastatic pancreatic cancer. There is scarcity of data regarding efficacy and toxicity profile of this combination in Indian population. Aims and Objectives The primary aim of this study was to assess efficacy of this regimen, for which evaluation done in terms of the objective response rate, progression-free survival (PFS), and overall survival. Safety data were also evaluated. Materials and Methods In this prospective study, gemcitabine plus nab-paclitaxel combination chemotherapy was given as first line in metastatic pancreatic carcinoma patients till progression or appearance of grade 3/4 toxicities with treatment. Results The study was performed in 30 patients comprising 18 (60%) males and 12 (40%) females. The median age was 60 years. Median number of cycles administered were six cycles per patient. Seventeen patients (56.67%) had a partial response and 0% had complete response. A total of seven (23.3%) patients progressed on chemotherapy and six (20%) had stable disease (SD). The disease control rate (responses and SD) was 76.7%. The median PFS was 5.75 months. There was no statistically significant difference in terms of response rates and baseline CA 19-9 levels. Most common toxicities were hematological toxicities with rates of grade 3/4 anemia and neutropenia of 20%. Among nonhematological toxicities, nausea (46.67%) and fatigue (30%) were the commonest. Conclusion Combination of gemcitabine and nab-paclitaxel is active and well tolerated in advanced pancreatic carcinoma. To the best of our knowledge, this is the first such study conducted in India.

Oxaliplatin, 5-fluorouracil, and folinic acid as first-line chemotherapy for elderly patients with advanced gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14155-14155 ◽  
Author(s):  
I. Choi ◽  
K. Lee ◽  
D. Oh ◽  
J. Kim ◽  
S. Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Elderly Patients ◽  
Folinic Acid ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
First Line ◽  
Line Chemotherapy

14155 Background: We investigated the efficacy and safety of an oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) as first-line chemotherapy for elderly patients with advanced gastric cancer. Methods: Chemotherapy-naïve patients (≥65 yr of age) with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Chemotherapy consisted of oxaliplatin 100 mg/m2 and FA 100 mg/m2 (2-hour intravenous infusion), then 5-FU 2400 mg/m2 (46-hour continuous infusion) every 14 days. Results: A total of 24 patients were enrolled between September 2003 and July 2005. Of 22 evaluable patients, none achieved complete response (CR) and 11 achieved partial response (PR), resulting in an overall response rate of 50%. Median progression-free survival (PFS) was 5.4 months (95% CI: 5.1–5.8 months) and median overall survival (OS) was 7.4 months (95% CI: 4.4–10.4 months). The main toxicities were anemia and leucopenia, which were observed in 39.8% and 19.0%, respectively, of the total cycles administered. There were 2 cycles of grade 4 leucopenia and febrile neutropenia was not observed. Conclusions: This oxaliplatin/5-FU/FA regimen shows good efficacy and an acceptable toxicity profile in elderly patients with advanced gastric cancer. No significant financial relationships to disclose.

Phase II study of oxaliplatin-based chemotherapy in patients with advanced gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14119-14119
Author(s):  
E. Vattemi ◽  
R. Pedersini ◽  
B. Kildani ◽  
J. Stocker ◽  
S. Baier ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Progression ◽  
Advanced Gastric Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
Median Number ◽  
Clinical Activity ◽  
Who Grade ◽  
Number Of Cycles

14119 Background: The aim of the study was to assess the toxicity and the clinical activity of oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks in patients with advanced gastric cancer. Methods: 26 patients with recurrent and/or metastatic gastric cancer were enrolled. They received oxaliplatin 85 mg/mq on day 1, FA 200 mg/mq as a 2 h infusion followed by bolus 5-FU 400 mg/mq repeated for 2 consecutive days (FOLFOX-4). Treatment was repeated every two weeks until disease progression or limiting toxicity. Results: Patients had a median age of 62 years (range, 74–40); 19 patients had a PS of 0–1. Twenty patients had a newly diagnosed metastatic disease and 6 patients had recurrent disease. The median number of sites involved was 2. Four patients had prior adjuvant chemotherapy with cisplatin, 5-FU and epirubicin. So far, 22 of 26 patients are evaluable. The mean number of cycles was 8.6 (range, 2–15). One complete response (4.5%) and 9 partial responses (41%) were observed for an overall response rate of 45%. Stable disease was seen in 8 patients (36%) and disease progression occurred in 4 patients (18%) Median progression free survival was 4.7 months and median overall survival was 9.8 months. No WHO grade IV toxicity occurred and the only grade III toxicity was peripheral neuropaty (10%). The most commonly reported hematologic event was grade II neutropenia (20%) and trombocytopenia (15%). Conclusions: FOLFOX-4 regimen shows good efficacy and accetable safety profile in advanced gastric patients. No significant financial relationships to disclose.

scholarly journals Second-Line Irinotecan, Leucovorin, and 5-Fluorouracil for Gastric Cancer Patients after Failed Docetaxel and S-1

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Joo Young Jung ◽  
Min-Hee Ryu ◽  
Baek-Yeol Ryoo ◽  
Boram Han ◽  
Ji Woong Cho ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Antitumour Activity ◽  
Metastatic Gastric Cancer ◽  
Second Line ◽  
First Line ◽  
Previously Treated ◽  
Grade 3 ◽  
Gastric Cancer Patients

Background.This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS).Patients and Methods.We reviewed the data of patients who had previously been treated with first-line DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011.Results.A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1–22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82–5.80) months and 6.24 (95% CI, 1.44–11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%).Conclusion.FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients.

Topotecan (T) and carboplatin (C) in the treatment of platinum sensitive relapsed ovarian cancer (ROC): Results of a multicenter phase I/II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5089-5089
Author(s):  
D. Koensgen ◽  
A. Belau ◽  
P. Klare ◽  
T. Steck ◽  
O. Camara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Remission Rate ◽  
Primary Standard ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Median Number ◽  
Hematological Toxicity ◽  
Platinum Sensitive ◽  
Grade 3

5089 Background: Despite of the effectiveness of radical surgery and first-line chemotherapy, most patients (pts) with advanced ovarian cancer will relapse. Paclitaxel (P) in combination with C as second-line treatment improves the outcome of pts with platinum-sensitive ROC in comparison to C monotherapy. Due to polyneuropathy and alopecia this regimen can not be offered to all pts. Therefore, other platinum-combinations are required. We conducted a phase I/II study to define the dose limiting toxicities (DLT) and the tolerability of combination therapy with T and C. Methods: Pts with platinum-sensitive ROC and primary standard therapy were stratified according to treatment-free interval (TFI): 6–12 months (A) and ≥12 months (B). Following dose regimens were analysed: T 1mg/m2/d1–3 + C AUC5/d3 and T 0.75 mg/m2/d1–3 + C AUC5/d3, q21d. DLT was based on the first 4 courses and defined as: CTC grade 3/4 hematological and grade 2 non-hematological toxicity (excepted alopecia, vomiting), treatment delay >7d. Primary endpoints were DLT and tolerability. Secondary endpoints were remission rate (RR) and progression-free survival (PFS). Results: From 06/04 to 08/05, 28 pts were enrolled, 26 pts (A:13 pts, B:13 pts) were eligible. Median age was 61.5 years. A total of 141 cycles were analysed, median number of cycles was 6 (range A:2–8, B:1–10). DLTs were: leucopenia (n = 5) and thrombocytopenia (n = 1). MTD was reached at dose: T: 0.75mg/m2 and C: AUC5. Overall, grade 3/4 hematologic toxicities (in% of all cycles), for (A) and (B) respectively, were: anemia 4% vs. 4%, leucopenia 34% vs. 13%, neutropenia 30% vs. 31%, thrombocytopenia 7% vs. 6%. Febrile neutropenia 4.3% vs. 0%. Darbepoetin alfa was given in 13.5% of all cycles. Overall, grade 3/4 non-hematologic toxicities were infrequent (< 5%). Overall RR (95% CI) was 50% (29.7–70.1) [A: 30.8% (0.1–61.1), B: 69.3% (38.7–90.9)]. Median follow-up was 5.8 mo, median PFS (95% CI) was 7.7 mo (1.3–9.4) [A: 6.2 (1.3–7.2), B: 8.0 (7.3–9.4)]. Median overall survival was not reached. Conclusions: TC is a feasible and effective chemotherapy regimen for platinum sensitive ROC. Tolerability is not associated to TFI. The recommended dose for subsequent studies is T:0.75 and C:AUC5. No significant financial relationships to disclose.

Docetaxel, oxaliplatin, and capecitabine (TEX regimen) for patients with metastatic gastric cancer: Interim results from a phase II trial by the German AIO Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4554-4554 ◽  
Author(s):  
M. H. Moehler ◽  
P. Thuss-Patience ◽  
D. Arnold ◽  
W. Grothe ◽  
A. Stein ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Response Assessment ◽  
Metastatic Gastric Cancer ◽  
Phase Ii Trials ◽  
Grade 3 ◽  
Ecog Ps

4554 Background: Combination regimens of 3 drugs have shown promising activity as treatment for patients (pts) with metastatic gastric cancer (GC). Docetaxel combined with cisplatin and 5-FU (CF) improved overall survival and response rates when compared to standard CF. However, the identification of less toxic and more convenient variants of this regimen is still important. We have previously established a regimen with docetaxel (T) combined with oxaliplatin (E) and capecitabine (X) in a phase I trial [Grothe et al., Proc. ASCO 2006]. Results of a preplanned interim analysis of subsequent multicenter phase II trials of the TEX regimen are presented here. Methods: Pts with metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, and no prior chemotherapy for advanced disease (adjuvant allowed) were enrolled. TEX regimen was administered as defined: T 35 mg/m2 and E 70 mg/m2 on days (d) 1 and 8, with X 800 mg/m2 bid on d1–14 every 22 days Toxicity assessment was done 3-weekly while CT scans were repeated 9-weekly. Results: 35 of 48 pts were enrolled until 06/08: 28 male / 7 female, median age 59 (36–81) years, ECOG PS 0/1/2 69%/31%/0%, gastric / gastroesophageal cancer 60%/40%, distant metastases 96%, tumor in situ 37%. The most common toxicities reported were (CTC grade [gr] 3/4): diarrhea 20%/3%, vomiting 11%/3%, asthenia and neurotoxicity each 9%/0%. Mucositis and hand-foot-syndrome were observed in (grade 1+2 / grade 3) 29%/0% and 26%/3%, respectively. Hematoxicity was mild with grade 3 anemia in 10% and no other grade 3/4 toxicity except one episode of febrile neutropenia . Of 25 pts evaluable so far, first tumor response assessment revealed (RECIST criteria) partial response in 36% and stable disease in 40% of patients. Conclusions: TEX is a safe and tolerable regimen for patients with metastatic gastric cancer. Preliminary efficacy results indicate promising activity. Mature data including progression free survival will be presented at the meeting. [Table: see text]

Olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer: A randomized, double-blind phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4013-4013 ◽  
Author(s):  
Yung-Jue Bang ◽  
Seock-Ah Im ◽  
Keun-Wook Lee ◽  
Jae Yong Cho ◽  
Eun-Kee Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Double Blind ◽  
Protein Levels ◽  
Common Grade ◽  
Atm Protein ◽  
Grade 3

4013 Background: Our multicenter study compared the efficacy of the oral PARP inhibitor olaparib plus paclitaxel (O/P) vs paclitaxel alone (P) as second-line therapy in pts with recurrent/metastatic gastric cancer (GC) (NCT01063517). As initial preclinical data suggested that responsiveness of GC cell lines to olaparib was associated with low ATM protein levels, our study was enriched for pts with low ATM tumors (ATM–) by IHC (50% randomized vs 14% screening prevalence). Methods: Eligible pts were randomized 1:1 (stratified by ATM status) to receiveolaparib 100 mg bid (tablet form) plus paclitaxel (80 mg/m2 iv on days 1, 8, 15 per 28-day cycle) or placebo plus paclitaxel until progression or investigator decision. After combination therapy, pts could take olaparib 200 mg bid monotherapy or placebo until progression. Co-primary endpoints: progression-free survival (PFS; RECIST v1.1) in all pts and ATM– pts. Secondary endpoints: overall survival (OS), objective response rate (ORR), safety. Results: 123/124 randomized pts were treated (O/P=61; P=62). Baseline characteristics were generally well balanced. Use of post-progression therapy was similar in both arms (O/P=48.4%; P=43.5%) as was median paclitaxel duration (O/P=17 wks; P=16 wks); 18 pts received monotherapy (O/P=11; P=7). More pts in the O/P than P arm had delays (79 vs 63%) and reductions (41 vs 27%) in paclitaxel dosing. The most common grade ≥3 AEs in the O/P and P arms were neutropenia (56 vs 39%) and anemia (11 vs 11%). Conclusions: Olaparib plus paclitaxel was well tolerated and led to a statistically significant improvement in OS, but not PFS, vs paclitaxel alone in both all pts and ATM– pts, with a larger benefit in ATM– pts. Clinical trial information: NCT01063517. [Table: see text]

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