Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer

Purpose TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer. Patients and Methods Patients were randomly assigned 1:1:1 to gemcitabine (1,000 mg/m2), gemcitabine plus TH-302 240 mg/m2 (G+T240), or gemcitabine plus TH-302 340 mg/m2 (G+T340). Randomized crossover after progression on gemcitabine was allowed. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, CA 19-9 response, and safety. Results Two hundred fourteen patients (77% with metastatic disease) were enrolled between June 2010 and July 2011. PFS was significantly longer with gemcitabine plus TH-302 (pooled combination arms) compared with gemcitabine alone (median PFS, 5.6 v 3.6 months, respectively; hazard ratio, 0.61; 95% CI, 0.43 to 0.87; P = .005; median PFS for metastatic disease, 5.1 v 3.4 months, respectively). Median PFS times for G+T240 and G+T340 were 5.6 and 6.0 months, respectively. Tumor response was 12%, 17%, and 26% in the gemcitabine, G+T240, and G+T340 arms, respectively (G+T340 v gemcitabine, P = .04). CA 19-9 decrease was greater with G+T340 versus gemcitabine (−5,398 v −549 U/mL, respectively; P = .008). Median OS times for gemcitabine, G+T240, and G+T340 were 6.9, 8.7, and 9.2 months, respectively (P = not significant). The most common adverse events (AEs) were fatigue, nausea, and peripheral edema (frequencies similar across arms). Skin and mucosal toxicities (2% grade 3) and myelosuppression (55% grade 3 or 4) were the most common TH-302–related AEs but were not associated with treatment discontinuation. Conclusion PFS, tumor response, and CA 19-9 response were significantly improved with G+TH-302. G+T340 is being investigated further in the phase III MAESTRO study (NCT01746979).

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PANOVA: A phase II study of TTFields (150 kHz) concomitant with standard chemotherapy for front-line therapy of advanced pancreatic adenocarcinoma—Updated efficacy results.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15790 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15790-e15790 ◽

Cited By ~ 2

Author(s):

Manuel Benavides ◽

Carmen Guillen ◽

Fernando Rivera ◽

Javier Gallego ◽

Jose A. Lopez-Martin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Metastatic Disease ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Skin Toxicity ◽

Distant Metastases ◽

Phase Iii ◽

Prior Therapy ◽

Grade 3

e15790 Background: TTFields are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. PANOVA was the first trial testing TTFields in pancreatic cancer patients. Results from the first arm of the study, testing TTFields in combination with gemcitabine, have demonstrated superiority in efficacy compared to historical controls (Rivera F. et al, J Clin Oncol 34, 2016 (suppl 4S; abstr 269). Methods: Twenty advanced pancreatic cancer patients were enrolled in the second arm of PANOVA and treated with TTFields in combination with gemcitabine concomitant to nab-paclitaxel. All patients had unresectable tumors, an ECOG performance score of 0-1 and no prior therapy. The primary endpoint was the incidence and severity of adverse events. Results: The median age was 68.2 (range – 58-81) and most patients (65%) had an ECOG score of 1. Twelve patients (60%) had distant metastases. Ten patients (50%) had serious AEs during the study period. Eleven patients (55%) had treatment-related skin toxicity, of which 5 had grade 3 toxicity. No TTFields-related serious AEs were reported. The median PFS was 12.7 months (95% CI 5.4, NA): 9.3 months in patients with metastatic disease, and not reached in locally-advanced patients. PFS rate at 6 months was 65%: 50% in metastatic disease and 87.5% in locally advanced patients. Of the evaluable tumors, 40% had partial response and another 47% stable disease. The median OS was not reached, and the 1-year survival rate was 72% (62.5% in metastatic disease and 87.5% in locally advanced disease). Conclusions: TTFields concomitant to gemcitabine and nab-paclitaxel are safe for advanced pancreatic cancer patients, with promising clinical outcome which doubled historical data. A phase III trial is planned, testing the efficacy of TTFields combined with gemcitabine and nab-paclitaxel in locally-advanced pancreatic cancer patients. Clinical trial information: NCT01971281.

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Gemcitabine in Combination With Oxaliplatin Compared With Gemcitabine Alone in Locally Advanced or Metastatic Pancreatic Cancer: Results of a GERCOR and GISCAD Phase III Trial

Journal of Clinical Oncology ◽

10.1200/jco.2005.06.023 ◽

2005 ◽

Vol 23 (15) ◽

pp. 3509-3516 ◽

Cited By ~ 646

Author(s):

C. Louvet ◽

R. Labianca ◽

P. Hammel ◽

G. Lledo ◽

M.G. Zampino ◽

...

Keyword(s):

Pancreatic Cancer ◽

Clinical Benefit ◽

Performance Status ◽

Combined Treatment ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Phase Iii ◽

Phase Iii Study ◽

Grade 3

Purpose Gemcitabine (Gem) is the standard treatment for advanced pancreatic cancer. Given the promising phase II results obtained with the Gem-oxaliplatin (GemOx) combination, we conducted a phase III study comparing GemOx with Gem alone in advanced pancreatic cancer. Patients and Methods Patients with advanced pancreatic cancer were stratified according to center, performance status, and type of disease (locally advanced v metastatic) and randomly assigned to either GemOx (gemcitabine 1 g/m2 as a 100-minute infusion on day 1 and oxaliplatin 100 mg/m2 as a 2-hour infusion on day 2 every 2 weeks) or Gem (gemcitabine 1 g/m2 as a weekly 30-minute infusion). Results Three hundred twenty-six patients were enrolled; 313 were eligible, and 157 and 156 were allocated to the GemOx and Gem arms, respectively. GemOx was superior to Gem in terms of response rate (26.8% v 17.3%, respectively; P = .04), progression-free survival (5.8 v 3.7 months, respectively; P = .04), and clinical benefit (38.2% v 26.9%, respectively; P = .03). Median overall survival (OS) for GemOx and Gem was 9.0 and 7.1 months, respectively (P = .13). GemOx was well tolerated overall, although a higher incidence of National Cancer Institute Common Toxicity Criteria grade 3 and 4 toxicity per patient was observed for platelets (14.0% for GemOx v 3.2% for Gem), vomiting (8.9% for GemOx v 3.2% for Gem), and neurosensory symptoms (19.1% for GemOx v 0% for Gem). Conclusion These results confirm the efficacy and safety of GemOx, but this study failed to demonstrate a statistically significant advantage in terms of OS compared with Gem. Because GemOx is the first combined treatment to be superior to Gem alone in terms of clinical benefit, this promising regimen deserves further development.

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

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.6 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 6-6 ◽

Cited By ~ 1

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]

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Phase II Trial of Bevacizumab Plus Gemcitabine in Patients With Advanced Pancreatic Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.01.9661 ◽

2005 ◽

Vol 23 (31) ◽

pp. 8033-8040 ◽

Cited By ~ 337

Author(s):

Hedy L. Kindler ◽

Gregory Friberg ◽

Deepti A. Singh ◽

Gershon Locker ◽

Sreenivasa Nattam ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Phase Ii ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Phase Iii ◽

Tumor Measurements ◽

Grade 3 ◽

Group B ◽

Endothelial Growth Factor

Purpose Vascular endothelial growth factor (VEGF) plays a key role in the biology and prognosis of pancreatic cancer. Inhibitors of VEGF suppress the growth of pancreatic cancer in preclinical models. The objectives of this phase II study were to assess the response rate and overall survival of pancreatic cancer patients who received gemcitabine with the recombinant humanized anti-VEGF monoclonal antibody bevacizumab. Patients and Methods Patients with previously untreated advanced pancreatic cancer received gemcitabine 1,000 mg/m2 intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Bevacizumab, 10 mg/kg, was administered after gemcitabine on days 1 and 15. Tumor measurements were assessed every two cycles. Plasma VEGF levels were obtained pretreatment. Results Fifty-two patients were enrolled at seven centers between November 2001 and March 2004. All patients had metastatic disease, and 83% had liver metastases. Eleven patients (21%) had confirmed partial responses, and 24 (46%) had stable disease. The 6-month survival rate was 77%. Median survival was 8.8 months; median progression-free survival was 5.4 months. Pretreatment plasma VEGF levels did not correlate with outcome. Grade 3 and 4 toxicities included hypertension in 19% of the patients, thrombosis in 13%, visceral perforation in 8%, and bleeding in 2%. Conclusion The combination of bevacizumab plus gemcitabine is active in advanced pancreatic cancer patients. Additional study is warranted. A randomized phase III trial of gemcitabine plus bevacizumab versus gemcitabine plus placebo is ongoing in the Cancer and Leukemia Group B.

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Randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer (JCOG1407).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4017 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4017-4017

Author(s):

Masato Ozaka ◽

Makoto Ueno ◽

Hiroshi Ishii ◽

Junki Mizusawa ◽

Hiroshi Katayama ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase Ii ◽

Primary Endpoint ◽

Response Rate ◽

Controlled Trial ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer ◽

Free Survival ◽

Randomized Phase Ii

4017 Background: FOLFIRINOX, consisting of leucovorin (LV), fluorouracil (FU), irinotecan (IRI) and oxaliplatin (L-OHP), and GnP, consisting of gemcitabine (GEM) plus nab-paclitaxel (nPTX), have shown superior efficacy over GEM in patients (pts) with metastatic pancreatic cancer. Although several studies have reported the efficacy of FOLFIRINOX or GnP for pts with locally advanced pancreatic cancer (LAPC), no randomized controlled trial to compare the two regimens has been conducted in those pts. To select the most promising chemotherapy for LAPC, a randomized phase II selection design trial (JCOG1407) was conducted to compare between modified FOLFIRINOX (FOLFIRINOX with dose reduction of IRI and without bolus FU; Arm A) and GnP (Arm B) for pts with LAPC. Methods: In Arm A, 85 mg/m2 of L-OHP, 200 mg/m2 of l-LV, 150 mg/m2 of IRI, followed by 2,400 mg/m2 of continuous FU over 46 hours are infused every 2 weeks. In Arm B, 125 mg/m2 of nPTX followed by 1,000 mg/m2 of GEM are infused on days 1, 8, and 15 every 4 weeks. The primary endpoint was overall survival (the proportion of 1-year OS), and secondary endpoints included progression-free survival (PFS), distant metastasis-free survival (MFS) and response rate in pts with target lesions. The planned sample size was 124 pts to select more effective regimen in 1-year OS with a probability of at least 0.85 and to test the null hypothesis of 53% in 1-year OS with a one-sided alpha of 5% and 80% Results: From 2015 to 2019, a total of 126 pts was enrolled from 29 Japanese institutions, and were allocated to Arm A (n = 62) or Arm B (n = 64). The median (range) age was 66 (44-75) years and 58.7% were male. At the analysis, after a median (range) follow-up of 1.52 (0.55-3.99) years, 75 (59.5%) pts died. The proportion of 1-year OS was better in Arm B, 77.4% [95% CI 64.9–86.0] vs. 82.5% [95% CI 70.7–89.9], but 2-year OS was better in Arm A, 48.2% [95% CI 33.3–61.7] vs. 39.7% [95% CI 28.6–52.5]. Median OS was 2.0 years [95% CI 1.6-2.7] in Arm A and 1.8 years [95% CI 1.5-2.0] in Arm B. 1-year PFS for Arm A/B was 47.5 % [95% CI 34.5-59.4]/40.2% [95% CI 27.8-52.3], and 1-year MFS was 64.2 % [95% CI 50.9-74.8]/57.3% [95% CI 43.9-68.6]. Arm A was better OS in pts with CA19-9 <1000 U/mL and the opposite trend was observed in pts with CA19-9>1000 U/mL. Response rate was 30.9% [95% CI 19.1-44.8] in Arm A, and 41.4% [95% CI 28.6-55.1]) in Arm B. Incidences of grade 3-4 non-hematological toxicities for Arm A and Arm B were 66.1% and 67.2%, respectively. There was no treatment-related death. Conclusions: This study was the first randomized trial comparing the two regimens. The 1-year OS of the primary endpoint in GnP was better than mFOLFIRINOX, but mFOLFIRINOX achieved longer survival in 2-year OS. It is required to confirm longer OS and safety profiles which regimen should be selected as a standard regimen in LAPC. Clinical trial information: jRCTs031180085.

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Randomized phase II study of gemcitabine monotherapy versus gemcitabine with an EPA-enriched oral supplement in advanced pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15109 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15109-e15109 ◽

Cited By ~ 1

Author(s):

Makoto Ueno ◽

Satoshi Kobayashi ◽

Shinichi Ohkawa ◽

Ryo Kameda ◽

Tomoko Andou ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Advanced Pancreatic Cancer ◽

Chemotherapeutic Agents ◽

Phase Iii ◽

Correct Selection ◽

Selection Probability ◽

Randomized Phase Ii ◽

Oral Supplement

e15109 Background: Gemcitabine is one of the standard chemotherapeutic agents for pancreatic cancer. Pancreatic cancer is often associated with cachexia. It had been reported that eicosapentaenoic acid (EPA) reduces proinflammatory cytokines, leading to improvement of cachexia. This study aimed to evaluate the efficacy and safety of gemcitabine with an EPA-enriched oral supplement in patients with unresectable pancreatic cancer. Methods: This phase II study consisted of patients (pts) who were randomly categorized into Arm A (1000 mg/m2 gemcitabine was administered on days 1, 8, and 15, every 4 weeks while an EPA-enriched oral supplement (Prosure, EPA 1056mg per pack) was taken daily at the maximum of 2 packs) or Arm B (gemcitabine monotherapy) at a 2:1 ratio. The primary endpoint was the evaluation of the 1-year survival. The sample size of 66 pts was chosen based on the randomized phase II selection design by Simon et al. (1985). The design suggests a correct selection probability of 80% if 1-year survival probabilities are 35% and 25% for two treatment arms. Results: From May 2010 to Oct. 2011, randomized 66 pts were examined (Arm A: 43, B: 23). The 1-year survival probability of Arm A was 35% while Arm B was 19%. The median survival times were 8.2 and 9.7 months, respectively. The hazard ratio was 0.79 [95%CI 0.46-1.37]; (p=0.40). The toxicities were mild and insignificant in both arms. Grade 3/4 toxicities (A/B %) included: neutropenia, 20.9/13.0; leukocytopenia, 30.2/21.7; hemoglobin, 14.0/8.7; thrombocytopenia, 9.3/8.7; nausea, 11.6/0.0; and diarrhea, 0/4.3. Although survival curve did not show significant differences, delayed effect was observed in Arm A. According to subgroup analyses, more beneficial effects were observed in men and pancreatic body-tail patients who took a lot of supplements (Table). Conclusions: Gemcitabine with an EPA-enriched oral supplement in advanced pancreatic cancer may be effective, and further phase III trial is needed. Clinical trial information: UMIN000003658. [Table: see text]

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Phase II study of alternate-day oral therapy with S-1 for unresectable advanced pancreatic cancer: An updated report.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.252 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 252-252

Author(s):

Sohei Satoi ◽

Motoki Miyazawa ◽

Masaji Tani ◽

Manabu Kawai ◽

Seiko Hirono ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Effects ◽

Phase Ii ◽

Primary Endpoint ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Final Analysis ◽

Current Data ◽

Standard Regimen ◽

Grade 3

252 Background: Based on the results of GEST, S-1 was confirmed to be non-inferior to gemcitabine. However, the recommended regimen of 4 weeks of administration interrupted by 2 weeks of drug withdrawal frequently causes adverse effect. Grade3/4 toxicities (%) in S-1 were neutropenia 8.8, anorexia 11.4, diarrhea 5.5. On the other hand, we experienced in clinical practice that the alternate-day administration of S-1 reduced adverse effects and was tolerable for unresectable advanced pancreatic cancer patients unwilling to continue the standard daily administration. We therefore conducted a multi-center cooperative prospective study to compare daily with alternate-day administration of S-1 for unresectable advanced pancreatic cancer. Methods: Patients with unresectable advanced pancreatic cancer (PS, 0 to 1; age, 20 to 80 years; no other therapy) were eligible for enrollment in this trial. S-1 was administered a dose of 40 to 60 mg twice daily, assigned according to body-surface area, on Monday, Wednesday, Friday, and Sunday (specified days). Each treatment cycle will be 42 days (6 weeks). The primary endpoint was overall survival (OS). Secondary endpoints were safety, response rate (RR), progression free survival (PFS), time to treatment failure (TTF). Results: A total of 50 patients were enrolled from Sep 2009 to Feb 2011. 48 patients were evaluable for response. Male/Female was 21/27, PS: 0/1 was 40/8. With a median follow-up time of 28.2 months, OS as primary endpoint was 8.4 months (95% CI, 5.4-10.8) with the 1 year survival rate 29.2%. PFS was 5.5 months, and TTF was 3.9 months. RR was 10.4% (95% CI: 3.5-19.1), and Disease Control rate was 79.2%. Grade 3/4 hematological and non-hematological toxicities were minor. All of those adverse reactions were tolerable and reversible. Conclusions: We will report the data from the final analysis at this meeting. The current data show mitigation of adverse effects with alternate-day administration of S-1, and it appears to be a more sustainable option for unresectable advanced pancreatic cancer. A randomized phase II trial comparing this regimen of S-1 with standard regimen of S-1 is ongoing. Clinical trial information: 000003453.

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Activity and safety of Nab-FOLFIRI and Nab-FOLFOX as first-line treatment for metastatic pancreatic cancer (phase II NabucCO study).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.351 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 351-351 ◽

Cited By ~ 1

Author(s):

Elisa Giommoni ◽

Evaristo Maiello ◽

Vanja Vaccaro ◽

Ermanno Rondini ◽

Caterina Vivaldi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase Ii ◽

Progression Free Survival ◽

Maximum Tolerated Dose ◽

Dose Finding ◽

Phase Iii ◽

Metastatic Pancreatic Cancer ◽

First Line ◽

Open Label ◽

Grade 3

351 Background: FOLFIRINOX is an approved regimen for metastatic pancreatic cancer (mPC). We performed a modification in FOLFIRINOX schedule, using nab-paclitaxel (nab-p) to obtain two regimens that could be as effective and less toxic than the original triplet. NabucCO study was a randomized phase II trial to assess activity and toxicity of nab-p instead of either oxaliplatin (Nab-FOLFIRI) or irinotecan (Nab-FOLFOX) in first line setting. Previous dose–finding NabucCO study defined that maximum tolerated dose of nab-p with FOLFIRI is 120 mg/m2, and with FOLFOX is 160 mg/m2. Methods: The study was a 1:1 parallel arm, open label, not comparative one to assess overall response rate (ORR) of Nab-FOLFIRI and Nab-FOLFOX as primary end-point. Patients (pts) with PS 0-1, untreated for mPC were randomized to receive leucovorin 400 mg/m2, 5FU bolus 400 mg/m2, 5FU 48h ci 2400 mg/m2, irinotecan 180 mg/m2 plus nab-p 120 mg/m2 (arm A) or leucovorin 400 mg/m2, 5FU bolus 400 mg/m2, 5FU 48h ci 2400 mg/m2 and oxaliplatin 85 mg/m2 iv plus nab-p 160 mg/m2 (arm B) every 2 weeks for up to 12 cycles. Secondary end points were clinical benefit rate (CBR), progression free survival (PFS), overall survival (OS), and safety. Results: From November 2015 to January 2017, 84 pts were treated (42 for each arm). Median age was 60 years (29-65) in arm A and 64 years (47-64) in arm B. The ORR was 31 % for both schedules, with a CBR of 69% and 71%, respectively. At a median follow-up of 11.4 months for arm A and 14.5 months for arm B (censored on august, 31th 2017), 1-year survival is 41% and 50%, respectively. For Nab-FOLFIRI PFS and mOS were 6 months (90% CI: 4.9-8.0) and 13.2 months (90% CI: 8.3-14.8), while in Nab-FOLFOX were 5.6 months (90% CI:4.9-7.2) and 10.8 months (90% CI: 8.4-12.8). Grade ≥3 toxicities in arm A were neutropenia (19%) and febrile neutropenia (12%). In arm B, main grade ≥3 toxicities were neutropenia (29%), fatigue (14%), peripheral neuropathy (7%). No toxic death were registered. Conclusions: Nab-FOLFIRI and Nab–FOLFOX demonstrated a similar activity to FOLFIRINOX, with better safety profile in terms of neutropenia, fatigue and neuropathy. These results could justify a future phase III evaluation. Clinical trial information: NCT02109341.

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Phase III Randomized Comparison of Gemcitabine Versus Gemcitabine Plus Capecitabine in Patients With Advanced Pancreatic Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.24.2446 ◽

2009 ◽

Vol 27 (33) ◽

pp. 5513-5518 ◽

Cited By ~ 484

Author(s):

David Cunningham ◽

Ian Chau ◽

Deborah D. Stocken ◽

Juan W. Valle ◽

David Smith ◽

...

Keyword(s):

Pancreatic Cancer ◽

Meta Analysis ◽

Performance Status ◽

Objective Response ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Primary Outcome Measure ◽

Phase Iii ◽

Open Label

PurposeBoth gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP).Patients and MethodsPatients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status ≤ 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted.ResultsBetween May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity.ConclusionOn the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.

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