scholarly journals Efficacy and safety profile of nab-paclitaxel plus gemcitabine in patients with metastatic pancreatic cancer treated to disease progression: a subanalysis from a phase 3 trial (MPACT)

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Arndt Vogel ◽  
Josefine Römmler-Zehrer ◽  
Jack Shiansong Li ◽  
Desmond McGovern ◽  
Alfredo Romano ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Disease Progression ◽  
Safety Profile ◽  
Metastatic Pancreatic Cancer ◽  
Efficacy And Safety ◽  
Phase 3

Overall survival from the phase 3 POLO trial: Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 378-378
Author(s):  
Talia Golan ◽  
Pascal Hammel ◽  
Michele Reni ◽  
Eric Van Cutsem ◽  
Teresa Macarulla ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Disease Progression ◽  
Metastatic Pancreatic Cancer ◽  
Rank Test ◽  
Primary Analysis ◽  
Multiple Testing Procedure ◽  
Phase 3 ◽  
Log Rank Test ◽  
Significant Difference

378 Background: POLO is the first phase 3 trial to evaluate maintenance therapy with the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib (O) in patients with metastatic pancreatic cancer (mPaC) and a germline BRCA mutation ( gBRCAm) whose disease had not progressed on first-line platinum-based chemotherapy (PBC). POLO demonstrated that patients had significantly longer progression-free survival (PFS; primary endpoint) with maintenance O than with placebo (P; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.35–0.82; p= 0.004). Herein, we present final overall survival (OS) data. Methods: POLO was a randomized, double-blind, placebo-controlled trial (NCT02184195) conducted at 119 sites in 12 countries. Eligible patients had mPaC without disease progression for ≥16 weeks on PBC and a deleterious or suspected deleterious gBRCAm. Patients were randomized 3:2 to O (300 mg tablet twice daily) or P. OS (time from randomization until death) was a key secondary endpoint assessed using a log-rank test. A multiple-testing procedure (MTP) was used, with alpha passed to OS owing to a significant PFS result. Time from randomization to second disease progression or death (PFS2), to discontinuation of treatment (TDT), and to initiation of first (TFST) or second (TSST) subsequent therapies following treatment discontinuation or death were secondary endpoints (log-rank test, not in MTP). Primary analysis of OS after 108 deaths; data cut-off (DCO) July 21 2020. Results: Ninety-two and 62 patients were randomized to O and P, respectively; those censored had a median follow-up of 31.3 months (mo) and 23.9 mo, respectively. At DCO, n = 13 remained on O; n = 2 on P. OS was similar for the O and P groups (median 19.0 and 19.2 mo, respectively; HR 0.83 favoring O; 95% CI 0.56–1.22; p= 0.3487). OS at 36 mo was 33.9% for O and 17.8% for P. Median PFS2 was 16.9 mo for O vs 9.3 mo for P (HR, 0.66; 95% CI 0.43–1.02; p= 0.0613). TFST, TSST and TDT were longer with O than P (Table). TDT at 24 mo was 24.3% for O vs 3.3% for P; at 36 mo was 17.2% for O vs 3.3% for P. Incidence of grade ≥3 adverse events (AEs) was 49% for O (anemia most common [12.2%]); 25% for P (anemia, hyperglycemia, upper abdominal pain most common [3.3%]). Treatment was discontinued owing to AEs for 8.9% patients in the O arm vs 1.6% for P. Conclusions: Although HR for OS was in favor of maintenance O vs P among patients with a gBRCAm and mPaC whose disease had not progressed during PBC, there was no statistically significant difference. PFS2 showed a clear trend for treatment benefit beyond disease progression in favor of O, but was not alpha protected. Safety data were consistent with the primary analysis. Clinical trial information: NCT02184195. [Table: see text]

A phase II study of S-1 in gemcitabine-refractory metastatic pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4115-4115 ◽  
Author(s):  
C. Morizane ◽  
T. Okusaka ◽  
J. Furuse ◽  
H. Ishii ◽  
H. Ueno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Primary Study ◽  
Standard Regimen

4115 Background: Gemcitabine (Gem) monotherapy or Gem-containing chemotherapy is the standard first line therapy for advanced pancreatic cancer. After disease progression, there is no standard regimen available. In a previous phase II trial (J. Furuse et al, Proc ASCO 2005: # 4104), S-1 has been reported to show considerable efficacy, achieving a response rate of 37.5% in chemo-naïve patients with pancreatic cancer. This study evaluated the efficacy and toxicity of S-1 in patients with Gem-refractory metastatic pancreatic cancer. Methods: Eligibility criteria were pathologically-proven pancreatic cancer with confirmation of progressive disease while receiving Gem-based chemotherapy, Karnofsky performance status 80 to 100%, age 20 to 74 years, with measurable metastatic lesions, adequate hematological, renal and liver functions, and written informed consent. S-1 was administered orally at 40 mg/m2 twice daily for 28 days with a rest period of 14 days as one course. Administration was repeated until the appearance of disease progression or unacceptable toxicity. The primary study end point was objective response, secondary end points included toxicity, progression-free survival (PFS) and overall survival, as well as clinical benefit response in symptomatic patients. Results: Forty patients (pts) from two institutions were enrolled between September 2004 and November 2005. Thirty-three pts are currently evaluable for response in this ongoing trial. There have been 5 confirmed partial responses (12.5%), and 14 pts (35%) with stable disease. Median survival has not been reached. Median PFS was 2.1 months. Toxicity data were available for 28 patients. Grade 3 and 4 toxicities were anemia (1 pts), appetite loss (2 pts), and fatigue (2 pts). Conclusions: Preliminary results demonstrated the safety and activity of S-1 in Gem-refractory metastatic pancreatic cancer. Efficacy and toxicity analysis are ongoing. Final results will be presented at the meeting. No significant financial relationships to disclose.

Larotrectinib efficacy and safety in adult TRK fusion cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3122-3122 ◽  
Author(s):  
David S. Hong ◽  
Shivaani Kummar ◽  
Anna F. Farago ◽  
Ulrik Niels Lassen ◽  
Jordan Berlin ◽  
...  
Keyword(s):  
Disease Progression ◽  
Safety Profile ◽  
Safety Data ◽  
Disease Status ◽  
Bone Sarcoma ◽  
Primary Diagnosis ◽  
Efficacy And Safety ◽  
Favorable Safety Profile ◽  
Duration Of Response ◽  
Favorable Safety

3122 Background: A broad range of pediatric and adult malignancies harbor TRK fusions involving the NTRK1, NTRK2, and NTRK3 genes. The highly-selective TRK inhibitor, larotrectinib, has previously shown a high overall response rate (ORR) and a favorable safety profile in patients (pts) with TRK fusion cancer. To better delineate efficacy in adults, as pediatric pts have a particularly high ORR, here we report updated efficacy and safety data from the adult subset of pts with TRK fusion cancer treated with larotrectinib. Methods: Adult pts (aged 18 or older) with TRK fusion cancer detected by local testing in 2 larotrectinib clinical trials (NCT02122913 and NCT02576431) were analyzed. Larotrectinib was administered 100 mg PO BID until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed by both investigator (INV) and independent assessment (IRC) using RECIST v1.1. Results: As of July 30, 2018, 83 adults (median age: 57 y, range 20–80 y) with TRK fusion cancer had been treated. Cancer types included salivary gland (23%) and thyroid cancer (19%), soft tissue sarcoma (14%), lung cancer (13%), colon cancer and melanoma (7% each), GIST (5%), and bone sarcoma, cholangiocarcinoma, and appendiceal, breast, and pancreas cancer (≤2% each). TRK fusions involved NTRK1 (40%), NTRK2 (2%), and NTRK3 (57%). 77% of pts had received prior systemic therapy (median lines: 2, range 0–10). In 74 pts evaluable per INV, the ORR was 76% with 9% CR, 57% confirmed PR, 9% PR pending confirmation, 12% SD, 11% PD, and 1% not determined; 9 pts were non-evaluable (NE) due to lack of post-baseline assessment. In 65 pts evaluable per IRC, the ORR was 68% with 17% CR, 51% PR, 15% SD, 12% PD, and 5% NE. With a median follow up of 17.2 and 17.5 mo per INV and IRC, respectively, the median duration of response had not been reached (ranges identical: 1.9+ to 38.7+ months). At data cutoff, 63% remained on treatment; 30% had discontinued due to disease progression. Adverse events were mostly grade 1–2. Conclusions: Larotrectinib demonstrated robust tumor-agnostic efficacy and a favorable safety profile in adult pts with TRK fusion cancer. These results support testing for TRK fusion cancer in pts with advanced solid tumors, regardless of site of primary diagnosis. Clinical trial information: NCT02122913 and NCT02576431.

PD-1 antibody combined with paclitaxel (albumin bound) and gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4665-TPS4665
Author(s):  
Jiujie Cui ◽  
Jiayu Yao ◽  
Yu Wang ◽  
Yiyi Liang ◽  
Yongchao Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Tumor Therapy ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Treatment

TPS4665 Background: Pancreatic cancer is a malignant tumor with limited therapeutic strategies and poor prognosis. About 60% of the patients have metastasis disease at time of diagnosis and lose the opportunity for surgery. Thus, therapy based on drugs becomes a vital part in pancreatic cancer. In 2013, MPACT showed that albumin-bound paclitaxel combined with gemcitabine in the treatment of metastatic pancreatic cancer could increase the mOS from 6.6 months to 8.7 months (HR = 0.72, 95% CI: 0.62-0.83; P < 0.001). Nowadays, the immunosuppressive checkpoint inhibitors acting on PD-1/PD-L1 pathway have shown a significant efficacy in enhancing tumor immune surveillance and anti-tumor immune response. In 2018, two studies reported in ASCO showed the preliminary efficacy of albumin paclitaxel, gemcitabine and PD-1 inhibitor in the treatment of advanced pancreatic cancer. Among patients who have not received treatment before, the disease control rate was even up to 100%. Therefore, this study will further explore the domestic PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as the first-line treatment of advanced pancreatic cancer among Chinese pancreatic cancer patients. Methods: This is a prospective, single-armed, exploratory, investigator initiated trial to explore the efficacy and safety of PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as first-line treatment of metastatic pancreatic cancer. This study is, to our knowledge, the first one to test the efficacy and safety of PD-1 antibody on metastatic pancreatic cancer patients among Chinese population. Survival index is median survival estimated by Kaplan-Meier and draw the survival curve. The response rate was compared by χ 2 test / Fisher test. All primary and secondary outcomes will be analyzed on the full analysis set. PD-1 antibody, 200mg, D1 administration; paclitaxel (albumin binding type), 125mg/m2, D1, 8 days administration; gemcitabine, 1000mg/m2, D1, 8 days administration, every 21 days as a cycle and PD-1 antibody (200mg, D1, every 21 days) single drug maintenance treatment is given after the completion of 6 cycle chemotherapy. Major eligibility criteria is that each participant must have metastatic pancreatic cancer confirmed by histology or cytology and has never received systemic anti-tumor therapy before. So far, 11 of planned 20 patients have been enrolled. Clinical trial information: NCT04181645 .

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