Phase III Randomized, Intergroup Trial Assessing Imatinib Mesylate At Two Dose Levels in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing the Kit Receptor Tyrosine Kinase: S0033

2008 ◽  
Vol 26 (4) ◽  
pp. 626-632 ◽  
Author(s):  
Charles D. Blanke ◽  
Cathryn Rankin ◽  
George D. Demetri ◽  
Christopher W. Ryan ◽  
Margaret von Mehren ◽  
...  
Keyword(s):  
Overall Survival ◽  
Gastrointestinal Stromal Tumors ◽  
Standard Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Free Survival ◽  
Stromal Tumors

PurposeTo assess potential differences in progression-free or overall survival when imatinib mesylate is administered to patients with incurable gastrointestinal stromal tumors (GIST) at a standard dose (400 mg daily) versus a high dose (400 mg twice daily).Patients and MethodsPatients with metastatic or surgically unresectable GIST were eligible for this phase III open-label clinical trial. At registration, patients were randomly assigned to either standard or high-dose imatinib, with close interval follow-up. If objective progression occurred by Response Evaluation Criteria in Solid Tumors, patients on the standard-dose arm could reregister to the trial and receive the high-dose imatinib regimen.ResultsSeven hundred forty-six patients with advanced GIST from 148 centers across the United States and Canada were enrolled onto this trial in 9 months. With a median follow-up of 4.5 years, median progression-free survival was 18 months for patients on the standard-dose arm, and 20 months for those receiving high-dose imatinib. Median overall survival was 55 and 51 months, respectively. There were no statistically significant differences in objective response rates, progression-free survival, or overall survival. After progression on standard-dose imatinib, 33% of patients who crossed over to the high-dose imatinib regimen achieved either an objective response or stable disease. There were more grade 3, 4, and 5 toxicities noted on the high-dose imatinib arm.ConclusionThis trial confirms the effectiveness of imatinib as primary systemic therapy for patients with incurable GIST but did not show any advantage to higher dose treatment. It appears reasonable to initiate therapy with 400 mg daily and to consider dose escalation on progression of disease.

scholarly journals Primary Clinical Response of Relmacabtagene Autoleucel in Adults with Relapsed/Refractory Follicular Lymphoma (r/r FL) in China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2434-2434
Author(s):  
Yuqin Song ◽  
Zhitao Ying ◽  
Haiyan Yang ◽  
Ye Guo ◽  
Wenyu Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Duration ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Free Survival ◽  
Duration Of Response

Abstract Background Most patients (pts) with r/r FL remain incurable and eventually relapse or progress. Previously, a Ph1 study of relma-cel (NCT03344367) had demonstrated preliminary safety and efficacy in r/r B-NHL pts, including those with r/r FL. A Ph2 pivotal study in r/r FL pts had been enrolled and preliminary efficacy, safety and PK was presented. Methods Adult pts were eligible with histologically confirmed grade (Gr)1-3a r/r FL on the basis of the 2016 WHO Classification, having failed ≥ 2-line prior therapies or relapsed after auto-HSCT, without allogeneic transplant within 90 days or primary central nervous system (CNS) lymphoma, and with ECOG performance score of 0-1. Pts were randomized to receive either 100×10 6 (low dose) or 150×10 6 (high dose) relma-cel (1:1) following fludarabine 25 mg/m 2 & cyclophosphamide 250 mg/m 2 daily×3. Pts were evaluated for efficacy (Cheson, 2014), toxicity (cytokine release syndrome [CRS] by Lee 2014, and others by CTCAE v4.03), and PK (by qPCR and flow cytometry). Primary endpoint was complete response rate (CRR). Secondary endpoints included objective response rate (ORR), frequency/severity of AEs, duration of response (DOR), duration of complete response (DoCR), duration of partial response (DoPR), time to primary remission (TTR), time to primary complete remission (TTCR), progression free survival (PFS), overall survival (OS), and CAR-T cell expansion. Disease response was by investigator assessment, a sensitivity analysis was also conducted using an independent review committee. Results Between June 2018 and June 2021, 28 r/r FL pts were enrolled and treated. As of the data cut-off of June 11, 2021, 20 pts were treated with relma-cel with ≥ 1 month of follow-up. Among these 20 pts, the median age was 54.5 years (range, 36-71), 50% of pts were male, 85% had ECOG 0, 10% had a sum of perpendicular diameters (SPD) ≥ 5000 mm 2, and 36% (5/14) had a FLIPI2 score≥ 3. Pts had received a median of 3.5 prior lines of therapy, 6 (30%) pts had received at least five lines of treatment and 65% were refractory to last prior treatment, 85% were relapsed, 50% were both relapsed and refractory. Relma-cel was successfully manufactured in all pts. Best ORR was 100% (19/19), and best CRR was 95% (18/19). For the mITT (n=19, one pt who developed gastric adenocarcinoma, was excluded, but also achieved CR), ORR at 1 month was 100%(19/19) and CRR was 63% (12/19). CRR at 3 months for 17 pts > 3 months post treatment, was 82%(14/17). At a median follow-up of 8.9 months, the median duration of response [DOR], progression-free survival (PFS) and overall survival (OS) were not reached. Twenty pts who received relma-cel were evaluable for safety. Gr ≥3 AEs related to relma-cel occurred in 80% of pts, most commonly neutrophil count decreased (35%), lymphocyte count decreased (30%) and white blood cell count decreased (25%). CRS occurred in 35% (all Gr 1), and only 2 pts received tocilizumab. Median CRS onset was 7 days (range, 5-9), with median duration of 5 days. Two (10%) pts experience neurotoxicity (NT), both Gr 1, with onsets of 4 and 9 days, and duration of 25 and 7 days, respectively. No deaths occurred. Safety data, tocilizumab/steroids usage and PK parameters are shown in the Table. Conclusion With median follow-up of 8.9 months, relma-cel treatment in r/r FL pts had resulted in high tumor remission rates and a manageable toxicity profile in the first 20 pts treated. Data for additional patients will be presented. Table： The summary of AEs (AE, TEAE, CRS, NT), the usage of tocilizumab/steroids and PK Parameters Figure 1 Figure 1. Disclosures Yang: JW Therapeutics: Current Employment. Zhang: JW Therapeutics: Current Employment. Ma: JW Therapeutics: Current Employment. Zhou: JW Therapeutics: Current Employment. Zheng: JW Therapeutics: Current Employment.

Efficacy of avelumab plus axitinib (A + Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 302-302
Author(s):  
Yoshihiko Tomita ◽  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Risk Factors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Risk Groups ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
To Receive

302 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated progression-free survival (PFS) and objective response rate (ORR) benefit across IMDC risk groups (favorable, intermediate, and poor) vs S in patients with previously untreated aRCC. Here we report efficacy of A + Ax vs S by number of IMDC risk factors (0, 1, 2, 3, and 4-6) and target tumor sites (1, 2, 3, and ≥4) at baseline from the second interim analysis of overall survival (OS). Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1) and OS were assessed. Results: At data cut-off (Jan 2019), median (m) follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by number of IMDC risk factors and target tumor sites at baseline. A + Ax generally demonstrated efficacy benefit vs S across subgroups. Conclusions: With extended follow-up, A + Ax generally demonstrated efficacy benefit vs S across the number of IMDC risk factors and tumor sites at baseline in aRCC. OS was still immature; follow-up for the final analysis is ongoing. Clinical trial information: NCT02684006 . [Table: see text]

scholarly journals Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

2017 ◽  
Vol 35 (17) ◽  
pp. 1905-1912 ◽  
Author(s):  
Emanuele Zucca ◽  
Annarita Conconi ◽  
Giovanni Martinelli ◽  
Reda Bouabdallah ◽  
Alessandra Tucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Trial ◽  
Lymphoid Tissue ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Final Sample ◽  
Phase Iii Study ◽  
To Receive

Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

Imatinib mesylate therapy in advanced gastrointestinal stromal tumors—A Regional cancer centre experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 19505-19505
Author(s):  
K. M. Patel ◽  
P. M. Shah ◽  
S. N. Shukla ◽  
B. J. Parikh ◽  
A. S. Anand ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Imatinib Mesylate ◽  
Metastatic Disease ◽  
Gastrointestinal Stromal Tumors ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stromal Tumors ◽  
Post Surgery

19505 Background: The treatment of gastrointestinal stromal tumors has been revolutionised by the advent of Imatinib, a specific tyrosine kinase inhibitor. Post operative local and metastatic recurrences of this tumor have been effectively managed by Imatinib. Here we present our experience of Imatinib in recurrent locally advanced/metastatic gastrointestinal stromal tumors (GIST). Methods: From Nov 2001 to Sep 2005, 33 patients with metastatic and / or locally advanced inoperable CD-117 positive GIST were offered imatinib mesylate therapy at 400 mg/day p.o. A total of 21 patients were evaluable for tumor response. Follow up period ranged from 4 months to 38 months with median follow up period being 18 months. Median age is 58 yrs, M:F ratio is 6:4. ECOG performance status was 0–1 in 70% (23 patients) and 2 in 30% (10 patients). 70% patients had post surgery recurrence. 2 patients (6%) had received adjuvant chemotherapy prior to recurrence. 30% (10 patients) had local recurrence, 40% (13 patients) had metastatic disease while 30% (10 patients) had local recurrence as well as metastatic disease. Results: Response evaluation was done by RECIST criteria. 15% (5 patient) showed CR while PR rates were 30% (10 patients). The overall major response (CR+PR) was 45%. The overall progression free survival was as high as 80%. All the patients who had a progression free survival also had a significant improvement in quality of life. Conclusions: Imatinib mesylate therapy shows significant survival benefits in locally advanced inoperable/metatstatic gastrointestinal stromal tumors. It will be a very long time before PET scan for evaluation and follow up becomes feasible in developing country setting. No significant financial relationships to disclose.

Randomized trial of high-dose chemotherapy with autologous haematopoietic stem cell support vs. standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: Overall survival after 6 years of follow up

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 672-672 ◽  
Author(s):  
A. R. Zander ◽  
N. Kroeger ◽  
C. Schmoor ◽  
W. Krueger ◽  
V. Moebus ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Standard Dose ◽  
Interactive Effect ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Grade Iii

672 Background: Investigation of high dose chemotherapy (HD-CT) supported by autologous hematopoietic stem cell transplantation compared with standard dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more axillary lymph nodes. Methods: Between November 1993 and September 2000 307 patients were randomized to receive the following cycles of Epirubicin (90 mg/m2), Cyclophosphamide (600 mg/m2) intervenously (every 21 days) either HD-CT of Cyclophosphamide (1500 mg/m2), Thiotepa (150 mg/m2) and Mitoxantrone (10 mg/m2) intervenously for 4 consecutive days followed by stem cell transplantation or standard dose chemotherapy SDCT in 3 cycles of Cyclophosphamide (500 mg/m2), Methotrexate (40 mg/m2) and Fluoruracil (600 mg/m2) intervenously on days 1 and 8 every 28 days. The primary end points were event-free survival and overall survival. Results: After a median follow-up of 6.1 years 166 events with respect to event-free survival (SD-CT: 91, HD-CT: 75) and 123 with respect to overall survival (SD-CT: 66 and HD-CT: 57) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0,80, p = 0,15. The hazard ratio for overall survival for high dose chemotherapy versus standard dose chemotherapy is estimated as 0,84, p = 0,33. Analysing the effect of treatment on event-free survival premenopausal patients, patients with tumor grade III and ER-positive patients had a better outcome with HD-CT with an interactive effect of 2.5 and 1.4. The significance was only shown in grade III patients in favour of HD-CT, (p = 0,049). The interactive effect of HD-CT with prognostic factors did not reach significance for overall survival. Conclusion: Even with a follow-up of 6.1 years there was only a trend in favour of high dose chemotherapy with respect to overall survival but without a statistical significance. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients which might benefit from this treatment approach. No significant financial relationships to disclose.

Treatment of nonresectable and metastatic gastrointestinal stromal tumors: Experience with the use of tyrosine kinase inhibitors in a third-level hospital in Mexico city.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 224-224
Author(s):  
Abdel Karim Dip Borunda ◽  
Alejandro J. Silva
Keyword(s):  
Overall Survival ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Gastrointestinal Stromal Tumors ◽  
Poor Prognosis ◽  
Kinase Inhibitors ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stromal Tumors

224 Background: Stromal tumors of the digestive tract are uncommon malignant diseases, and are subclassified as leiomyosarcomas and gastrointestinal stromal tumors (GIST) depending on the molecular expression of CD117 (KIT). GISTs represent 1% of malignant tumors affecting this anatomical site. Located diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since Tyrosine – kinase inhibitors were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. Methods: We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. Results: We obtained information of 71 patients with metastatic, nonresectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%), with median age of 58 years. Stage at diagnosis was predominantly metastatic (46.5%) most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 23.6m and overall survival was 81.3 months. All patients were initially treated with imatinib at a dose of 400mg per day. Treatment was well tolerated in most cases. Conclusions: Metastatic GIST evaluated in our center shows a different affection in gender and age, our population shows a different response to TKI’s, than reported in other series with superior overall survival, Poor prognosis is associated with lung affection. Biological studies will be started for the molecular evaluation of these tumors.

Efficacy of pembrolizumab (pembro) monotherapy versus chemotherapy for PD-L1–positive (CPS ≥10) advanced G/GEJ cancer in the phase II KEYNOTE-059 (cohort 1) and phase III KEYNOTE-061 and KEYNOTE-062 studies.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 427-427 ◽  
Author(s):  
Zev A. Wainberg ◽  
Charles S. Fuchs ◽  
Josep Tabernero ◽  
Kohei Shitara ◽  
Kei Muro ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Durable Response ◽  
Free Survival ◽  
Duration Of Response ◽  
Positive Score ◽  
Combined Positive Score

427 Background: Pts with advanced gastric/gastroesophageal junction (G/GEJ) cancer received pembro monotherapy (200 mg Q3W) 3L+ in cohort 1 of KEYNOTE-059 (NCT02335411), 2L in KEYNOTE-061 (NCT02370498), or 1L in KEYNOTE-062 (NCT02494583). We present efficacy data for patients with PD-L1 combined positive score (CPS) ≥10 tumors in these trials. Methods: In study 059, 46 pts in cohort 1 with PD-L1 CPS ≥10 received pembro. In study 061, 108 pts with PD-L1 CPS ≥10 received pembro (n=53) or chemotherapy (chemo; n=55). In study 062, 182 pts with CPS ≥10 received pembro (n=92) or placebo + chemo (n=90). Efficacy end points included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: Median follow-up in study 059 was 5.6 mo. Median OS with pembro was 7.9 mo (95% CI, 5.8-11.1), and 12-mo OS was 32.6%. PFS at 6 mo was 17.4%, ORR was 17.4%, and median DOR was 20.9 mo (2.8+ to 34.9+). In study 061, after a median follow-up of 8.8 mo, pembro prolonged OS vs chemo (median 10.4 vs 8.0 mo; HR, 0.64; 95% CI, 0.41-1.02); 12-mo OS was 45.3% for pembro and 23.6% for chemo. Median PFS was 2.7 mo for pembro and 3.4 mo for chemo (HR, 0.86; 95% CI, 0.56-1.33). ORR was 24.5% vs 9.1%, and median DOR was NR (4.1-26.0+) and 6.9 mo (2.6-6.9) for pembro vs chemo. In study 062, median follow-up was 17.4 mo for pembro and 10.8 mo for chemo. Pembro prolonged OS vs chemo (median 17.4 vs 10.8 mo; HR, 0.69; 95% CI, 0.49-0.97); 12-mo OS was 56.5% vs 46.7%. Median PFS was 2.9 mo vs 6.1 mo (HR, 1.09, 95% CI, 0.79-1.49). ORR was 25.0% vs 37.8%, and median DOR was 19.3 mo (1.4+ to 33.6+) vs 6.8 mo (1.5+ to 30.4+) for pembro vs chemo, respectively. Conclusions: Collectively, these data indicate that 1L, 2L, and 3L+ pembro monotherapy showed clinically meaningful efficacy in CPS ≥10, with a more durable response than chemotherapy. Clinical trial information: NCT02335411, NCT02370498, and NCT02494583. [Table: see text]

Results of a phase II study of capecitabine-based doublets in the treatment of metastatic triple-negative breast cancer (mTNBC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11538-e11538
Author(s):  
Ying Fan ◽  
Binghe Xu ◽  
Yuqian Liao ◽  
Fei Ma ◽  
Peng Yuan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cytotoxic Agents ◽  
Free Survival ◽  
Metastatic Setting ◽  
Secondary Endpoints

e11538 Background: It is extremely important to identify proper cytotoxic agents for TNBC which had limited choices except chemotherapy. Capecitabine are well established as a major chemotherapeutic agent in metastatic setting. The efficacy of capecitabine-based chemotherapy has not been prospectively studied in TNBC and data remains scant. This study was designed to investigate the efficacy of capecitabine-based doublets in the treatment of metastatic TNBC. Methods: Eligible metastatic TNBC women with measurable diseases were recruited to receive either TX regimen (docetaxel 75mg/m2 iv d1 plus capecitabine 1000mg/m2 bid, d1-14,q3w) or NX regimen (vinorelbine 25mg/m2 iv d1, 8 plus capecitabine 1000mg/m2 bid, d1-14, q3w) at the discretion of physicians for up to 6 cycles, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and secondary endpoints included progression free survival (PFS), overall survival (OS). Results: 45 mTNBC patients, 27 in TX and 18 in NX were recruited, mostly (73.3%) as 1st line and the remaining as the 2nd line. The total objective response rate was 20.0% and clinical benefit rate was 62.2%. After a median follow-up of 28 months, PFS was 5.2 months (95%CI, 4.1-6.3mons) and OS was 18.2months (95%CI, 8.7-27.7mons). Almost half of the patients (22/45) progressed during treatment or within one month of the treatment discontinuation. PFS was significantly longer if patients got CR/PR (9.6 vs 4.3mons, P=0.015). When comparing two doublets, the response rate was numerically but not statistically lower in TX group than in NX group (14.8% vs 27.8%, P=0.449). Similarly, no difference was found in either PFS (4.9 vs 5.2 mons, P=0.483) or OS (21.5 vs 18.3 mons, P=0.964) between two regimens. Conclusions: Although the overall survival seems to be reasonable, efficacy of capecitabine-contained TX or NX regimen was relatively poor in terms of tumor remission and progression free survival in mTNBC patients, suggesting capecitabine may have limited potency in this subtype. These two combinations may be considered to be acceptable but may not be recommended as prior choice for mTNBC patients.

Effect of baseline carbohydrate antigen 19-9 (CA19-9) level on overall survival (OS) in NAPOLI-1 trial: A phase III study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin (5-FU/LV), versus 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 425-425 ◽  
Author(s):  
Li-Tzong Chen ◽  
Jens T Siveke ◽  
Andrea Wang-Gillam ◽  
Richard Hubner ◽  
Shubham Pant ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Effect ◽  
Proportional Hazards ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Response To Therapy ◽  
Phase Iii ◽  
Free Survival ◽  
Previously Treated

425 Background: CA19-9 has been shown to correlate with response to therapy and OS in patients with mPAC. NAPOLI-1, a randomized phase 3 study evaluated nal-IRI, a nanoliposomal formulation of irinotecan, with or without 5-FU/LV vs 5-FU/LV in patients with mPAC previously treated with gemcitabine-based therapy. Nal-IRI+5-FU/LV significantly improved OS (primary endpoint) vs 5-FU/LV (6.1 mo vs 4.2 mo; unstratified hazard ratio [HR] = 0.67; P = 0.012). CA19-9 response (≥50% decline from baseline) was superior with nal-IRI+5FU/LV compared with 5-FU/LV (29% vs 9%; P=0.0006). Nal-IRI alone did not show a statistical improvement in survival. Methods: Patients with a recorded baseline CA19-9 measurement were divided into quartiles to evaluate the treatment effect pattern of CA19-9 from nal-IRI+5-FU/LV and 5-FU/LV arms. Quartile ranges were based on 404 available CA19-9 values from randomized patients (N=417). Unstratified Cox proportional hazards regression was used to estimate HRs and corresponding 95% CIs. Effect of baseline CA19-9 on time to response, progression-free survival, and response will be presented. Results: Of patients randomized to receive nal-IRI+5-FU/LV (n = 117) or 5-FU/LV enrolled contemporaneously (n = 119), 218 received study drug and had a baseline CA19-9 measurement. Results show a greater treatment effect on OS with higher CA19-9 level relative to 5-FU/LV. Conclusions: In patients with mPAC previously treated with gemcitabine-based therapy, nal-IRI+5-FU/LV significantly improved OS supported by progression free survival and objective response rate. The CA19-9 serum level can provide important information with regards to overall survival. Clinical trial information: NCT01494506. [Table: see text]

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