Subgroup analysis by baseline pain intensity (BPI) and analgesic use (BAU) in NAPOLI-1: A phase III study of liposomal irinotecan (nal IRI)±5-fluorouracil/ leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 379-379
Author(s):  
Teresa Mercade Macarulla ◽  
Jens T. Siveke ◽  
Andrew Peter Dean ◽  
Richard Hubner ◽  
Jean-Frédéric Blanc ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Prognostic Effect ◽  
Baseline Pain Intensity ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Recorded Data ◽  
Liposomal Irinotecan ◽  
Post Hoc

379 Background: We report an exploratory, post hoc subgroup analysis in pts with BPI and BAU data receiving nal-IRI+5-FU/LV, nal-IRI or 5-FU/LV in NAPOLI-1 (NCT01494506). In this pivotal trial, nal-IRI+5-FU/LV improved median OS (mOS) vs. 5-FU/LV (6.1 vs. 4.2 mo [HR=0.67; p=0.012]). Methods: BPI/BAU included an average of 3-7 days pt-recorded data before randomisation. Greater values indicated greater pain for BPI using a 100 mm visual analogue scale. BAU was converted to morphine equivalent mg/day. Results: Of 417 ITT pts, 295 had BPI and 299 had BAU data. Mean and median BPI were 28.6 and 25.0, respectively, and BAU were 33.3 and 8.1 mg/day, respectively. The percentage of pts with KPS ≥ 80 was higher in ≤ mean/≤ median (n=159/148) BPI groups vs. > mean/> median (n=136/147) BPI groups (96-97 vs. 83%) and in ≤mean/≤median (n=207/150) BAU groups vs. > mean/> median (n=92/149) BAU groups (95-97 vs. 82-85%). mOS and median PFS (mPFS) were higher for nal-IRI+5-FU/LV vs 5-FU/LV in all groups, with ≤ mean/≤ median BPI or BAU showing better outcomes vs. > mean/> median BPI or BAU (Table). Conclusions: BPI and BAU appear to have a prognostic effect on outcomes in mPDAC pts in the NAPOLI-1 study. No predictive effect was observed, with nal-IRI+5-FU/LV showing higher mOS vs. 5-FU/LV in all groups. Clinical trial information: NCT01494506. [Table: see text]

Subgroup analysis by measurable metastatic lesion (ML) number and selected lesion locations (LL) at baseline (BL) in NAPOLI-1: A phase III study of liposomal irinotecan (nal-IRI)±5-fluorouracil/leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 460-460
Author(s):  
Jens T. Siveke ◽  
Richard Hubner ◽  
Teresa Mercade Macarulla ◽  
Andrea Wang-Gillam ◽  
Andrew Peter Dean ◽  
...  
Keyword(s):  
Metastatic Lesion ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Pivotal Phase ◽  
Clear Trend ◽  
Prognostic Effect ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Liposomal Irinotecan ◽  
Post Hoc

460 Background: We report a post hoc, exploratory analysis of pts with BL ML number and LL data who received nal-IRI+5-FU/LV, nal-IRI or 5-FU/LV in NAPOLI-1, a pivotal, phase 3 trial (NCT01494506). nal-IRI+5-FU/LV increased median OS (mOS) vs 5-FU/LV (6.1 vs 4.2 mo [HR=0.67; p=0.012]). Methods: ML (1, 2, 3, >3) and LL were recorded (local investigator) at BL. Pts with >1 LL were counted for each location. Results: 354 of 417 ITT pts had measurable BL ML and 1,080 LL were recorded. There was no clear trend in the percentage of pts with KPS ≥80 in 1- >3 ML (range 87%-95%) or LL (range 89%-94%) subgroups. ML 1 (n=81), 2 (n=65) and 3 (n=24) subgroups were small. nal-IRI+5-FU/LV significantly improved mOS vs. 5-FU/LV in pts with 2/>3 ML (n=184/24); nal-IRI+5-FU/LV had numerically higher mOS vs. 5-FU/LV for all LL (Table). nal-IRI+5-FU/LV had favourable median PFS (mPFS) vs. 5-FU/LV in pts with 1–>3 ML (range 2.0-4.2 vs. 1.4-1.9 mo; HR range 0.35-0.88) and for all LL (range 2.8-4.2 vs. 1.4-2.0 mo; HR range 0.39-0.55). Conclusions: Low pt numbers across groups and repeat counting of pts in LL subgroups preclude firm conclusions on treatment efficacy, pending further analyses. Allowing for these limitations, we detected no clear prognostic effect on outcomes of higher BL ML number or LL in NAPOLI-1 ITT pts. nal-IRI+5-FU/LV improved mOS vs. 5-FU/LV in some ML groups and across LL groups; improvement in mPFS vs. 5-FU/LV in the ITT population was maintained in all subgroups. Clinical trial information: NCT01494506. [Table: see text]

Subgroup analysis by baseline (BL) weight-associated parameters: A phase III study of liposomal irinotecan (nal-IRI)±5-fluorouracil/leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based (gem) therapy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 410-410
Author(s):  
Teresa Mercade Macarulla ◽  
Richard Hubner ◽  
Jean-Frédéric Blanc ◽  
Andrea Wang-Gillam ◽  
Chung-Pin Li ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Analysis Data ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Independent Effect ◽  
P Value ◽  
Prognostic Impact ◽  
Value Range ◽  
Liposomal Irinotecan ◽  
Post Hoc

410 Background: We report prognostic evaluation of BL weight-associated parameters (body-mass index [BMI], body surface area [BSA] and weight) in pts with mPDAC after progression following gem-based therapy (NAPOLI-1 trial; NCT01494506). Pts received nal-IRI+5-FU/LV, nal-IRI monotherapy or 5-FU/LV in NAPOLI-1, an international, randomised, phase 3 trial; nal-IRI+5-FU/LV treatment resulted in a 45% increased median OS vs. 5-FU/LV (unstratified HR = 0.67; p = 0.012). Methods: This exploratory subgroup analysis compares outcomes by BL BMI, BSA and weight, using primary survival analysis data from the ITT population for all treatment arms combined (n = 417) and the nal-IRI+5-FU/LV arm on its own (n = 117). Results: OS and PFS were not significantly different between BL BMI, BSA and weight median subgroups in the entire NAPOLI-1 ITT population (HR range 1.06–1.15; log-rank p-value range 0.21–0.60; Table) and in the nal-IRI+5-FU/LV arm (HR range 0.94–1.19; log-rank p-value range 0.43–1.00). Conclusions: This post-hoc subgroup analysis did not detect any prognostic impact on treatment outcome by BL BMI, BSA and weight for mPDAC pts progressed following gem-based therapy. This observation rules out a treatment-independent effect. No evidence of a predictive effect on nal-IRI+5-FU/LV efficacy was found. Clinical trial information: NCT01494506. [Table: see text]

scholarly journals Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1284
Author(s):  
Nicolas Delanoy ◽  
Debbie Robbrecht ◽  
Mario Eisenberger ◽  
Oliver Sartor ◽  
Ronald de Wit ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Post Hoc Analysis ◽  
Psa Response ◽  
Phase Iii Study ◽  
Psa Progression ◽  
Previously Treated ◽  
Post Hoc

Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. Conclusions: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.

scholarly journals Nomogram for Predicting Survival in Patients Treated with Liposomal Irinotecan Plus Fluorouracil and Leucovorin in Metastatic Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1068 ◽  
Author(s):  
Chen ◽  
Macarulla ◽  
Blanc ◽  
Mirakhur ◽  
Jong ◽  
...  
Keyword(s):  
Carbohydrate Antigen ◽  
Phase Iii ◽  
Disease Stage ◽  
Ductal Adenocarcinoma ◽  
Karnofsky Performance Score ◽  
Neutrophil Lymphocyte Ratio ◽  
Baseline Factors ◽  
Liposomal Irinotecan ◽  
Aid Decision ◽  
Post Hoc

NAPOLI-1 (NCT01494506) was a phase III study of liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This post hoc analysis of NAPOLI-1 aimed to develop a predictive nomogram for overall survival (OS) at 6 and 12 months. Analyses were derived from all patients in NAPOLI-1 randomized to receive nal-IRI+5-FU/LV, nal-IRI monotherapy, or 5-FU/LV combination therapy. OS was associated with baseline factors using univariate and multivariable Cox analyses. A predictive nomogram was derived and validated using a concordance index and calibration plots. The univariate analyses identified 21 independent factors that contributed to OS, with eight factors significantly associated with OS. The Karnofsky Performance Score contributed the largest number of points (100), followed by presence of liver metastasis (98) and randomization to nal-IRI+5-FU/LV (96). The other baseline factors showing effects were albumin (g/dL), neutrophil/lymphocyte ratio, carbohydrate antigen 19-9 (U/mL), disease stage at diagnosis, and body mass index (kg/m2). The nomogram was used to predict the 6- and 12-month survival probability. The mean absolute errors between the observed and predicted probabilities for OS at 3, 6, and 9 months were 0.07, 0.08, and 0.07, respectively. This nomogram, based on NAPOLI-1, provides additional insight to aid decision-making for patients with mPDAC after previous gemcitabine-based therapy.

Subgroup analysis by prior lines of metastatic therapy (mtx) in NAPOLI-1: A global, randomized phase 3 study of liposomal irinotecan (nal-IRI) ± 5-fluorouracil and leucovorin (5-FU/LV), vs. 5-FU/LV in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have progressed following gemcitabine-based therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4127-4127
Author(s):  
Teresa Mercade Macarulla ◽  
Jens T. Siveke ◽  
Andrea Wang-Gillam ◽  
Chung-Pin Li ◽  
Gyorgy Bodoky ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Subgroup Analysis ◽  
Analysis Data ◽  
Ductal Adenocarcinoma ◽  
Phase 3 ◽  
Study Methodology ◽  
Liposomal Irinotecan ◽  
Grade 3 ◽  
Post Hoc ◽  
Clinical Trial Information

4127 Background: In the NAPOLI-1 study, nal-IRI+5-FU/LV significantly increased median OS vs. 5-FU/LV control (6.1 vs. 4.2 mo; unstratified HR = 0.67 [0.49–0.92]; p = .012). This is a subgroup analysis by prior lines of mtx. Methods: Study methodology has been published (Wang-Gillam; Lancet 2016). This exploratory subgroup analysis compares outcomes in pts with 0–1 vs. ≥2 prior mtx lines, based on primary survival analysis data (cut-off February 2014) of the ITT population. Results: OS, PFS and CA19-9 response rates in pts with 0–1 (65.8% of pts) or ≥2 (34.2%) prior mtx lines are shown (see Table). Median OS for nal-IRI+5-FU/LV improved vs. 5-FU/LV by 2.1 mo to 6.2 mo (HR = 0.66; p = .03) in pts with 0–1 prior mtx lines and by 1.1 mo to 5.4 mo (HR = 0.68; p = .18) in pts with ≥2 prior mtx lines. The safety profile was similar between subgroups with nal-IRI+5-FU/LV (≥grade 3 drug-related AEs: 43 [55%] with 0–1 and 20 [51%] with ≥2 prior mtx lines). Conclusions: This post-hoc subgroup analysis shows significant increases for nal-IRI+5-FU/LV over 5-FU/LV in OS, PFS and CA19-9 response in pts with 0–1 prior mtx lines. Median OS benefit was less prominent in later lines, but conclusions are restricted by limited pt numbers. Clinical trial information: NCT01494506. [Table: see text]

scholarly journals Application of two lines of chemotherapy: gemcitabine with nab-paclitaxel and liposomal irinotecan with 5-fluorouracil and leucovorin in patient with advanced pancreatic adenocarcinoma

Oncoreview ◽  
2021 ◽  
Vol 11 (3(43)) ◽  
pp. 68-72
Author(s):  
Krystyna Ostrowska-Cichocka ◽  
Marek Z. Wojtukiewicz
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Option ◽  
Advanced Pancreatic Cancer ◽  
Distant Metastases ◽  
Phase Iii ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Liposomal Irinotecan ◽  
Line Of Therapy ◽  
Advanced Pancreatic Adenocarcinoma

Pancreatic cancer is a disease with high mortality. It is predicted to become the second leading cause of cancer death in some regions of the world. Frequent diagnosis at an advanced stage contributes to 5-year survival at a highly unsatisfactory level of 2–9%. Due to the lack of early symptoms, nearly 80% of patients receive a diagnosis when distant metastases develop. So far, the most frequently used programs in the treatment of patients with pancreatic cancer in the stage of neoplastic spreading include: FOLFIRINOX (oxaliplatin, 5-fluorouracil, irinotecan, leucovorin), gemcitabine alone or in combination with nab-paclitaxel or erlotinib. Based on the results of the phase III study NAPOLI-1, liposomal irinotecan in combination with 5-fluorouracil (5-FU) and leucovorin (LV ) was approved as the first regimen for use in the second or subsequent line of therapy in patients with advanced pancreatic cancer previously treated with gemcitabine. This paper presents a case of a patient with advanced pancreatic cancer who was treated with two lines of chemotherapy – gemcitabine in combination with nab-paclitaxel and liposomal irinotecan with 5-FU/LV . The treatment was well tolerated and was considered a valuable therapeutic option. A 2-year overall survival was obtained from the diagnosis of the disease.

Exploratory analysis of survival benefit and prior docetaxel (D) treatment in COU-AA-301, a phase III study of abiraterone acetate (AA) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4558-4558 ◽  
Author(s):  
Oscar B. Goodman ◽  
Kim N. Chi ◽  
Arturo Molina ◽  
Christopher Logothetis ◽  
Robert J. Jones ◽  
...  
Keyword(s):  
Abiraterone Acetate ◽  
Phase Iii ◽  
Double Blind Study ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Survival Result ◽  
Castration Resistant ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Post Hoc

4558 Background: AA, a selective androgen biosynthesis inhibitor, blocks the action of CYP17, thereby inhibiting adrenal and intratumoral androgen production. AA has demonstrated improved overall survival (OS) by 4.6 months (mos) vs placebo (HR=0.74) in patients (pts) previously treated with D. Methods: COU-AA-301 is a randomized double blind study of AA (1 g) + P (5 mg po BID) vs placebo + P administered to mCRPC pts post-D with a primary endpoint of OS. To further evaluate primary survival result robustness, we performed post hoc exploratory analyses to assess whether the timing of first and last dose of D and reason for D discontinuation impacted OS. Results: At randomization, treatment arms were balanced with respect to baseline characteristics, prior D use, and reasons for discontinuation. In both arms, almost half (45%) discontinued D due to progressive disease (PD); remainder discontinued D after completing all planned cycles (37%), due to toxicity (12%), or for other reasons (5%) per investigator. Median OS from first and last dose of D were longer with AA vs placebo (Table). Median OS was longer with AA vs placebo in pts who discontinued D for PD, or for all other reasons. Conclusions: These exploratory analyses suggest that the OS benefit of AA in mCRPC was maintained when calculated from first or last dose of prior D, and whether or not pts discontinued D for PD. Pts in AA arm of this study had a prolonged median OS of > 32 mos from time of initial D therapy. Congruity among these analyses and lack of dependence on D timing demonstrate robustness of the primary survival result. [Table: see text]

Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first disease progression (PD) in patients with metastatic colorectal cancer (mCRC) previously treated with BEV-based therapy: Outcomes according to KRAS status and first-line CT backbone in the ML18147 study.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 520-520 ◽  
Author(s):  
Stefan Kubicka ◽  
Richard Greil ◽  
Thierry André ◽  
Jaafar Bennouna ◽  
Javier Sastre ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Therapy Outcomes ◽  
First Line ◽  
Mutant Type ◽  
Post Hoc Analysis ◽  
Kras Status ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Post Hoc

520 Background: ML18147 is the first randomized phase III study to show that continuing BEV + standard CT as second-line (2L) treatment significantly improves overall survival (OS) and progression-free survival (PFS) in patients with mCRC who progressed after receiving a standard first-line (1L) BEV-containing regimen. Here we report an exploratory analysis of outcomes based on CT backbone and KRAS status. Methods: Patients with unresectable, histologically confirmed mCRC who progressed ≤3 months after discontinuing 1L BEV were randomised to 2L CT (crossed over from oxaliplatin to irinotecan and vice versa) ± BEV. This post-hoc analysis evaluated OS, PFS, overall response rate (ORR) and disease control rate (DCR) according to 1L CT backbone (irinotecan- or oxaliplatin-based) and KRAS status (Scorpion ARMS test for KRAS codons 12 and 13). Results: In total, 616 patients (75% of the ITT population) were included in this analysis; 316 had wild-type (WT) and 300 had mutant-type (MT) KRAS status; 355 received 1L irinotecan and 261 received 1L oxaliplatin. BEV+CT beyond PD prolonged OS and PFS vs CT alone, regardless of whether oxaliplatin- or irinotecan-based CT was used in the 1L and whether patients had WT or MT KRAS (Table). Adverse events were not increased when continuing BEV+CT beyond PD and were consistent with previous findings. Conclusions: This post hoc analysis suggests that continuing BEV + 2L oxaliplatin or irinotecan-based CT (following crossover) leads to prolonged OS and PFS, regardless of KRAS status or if oxaliplatin or irinotecan-based CT was used in the 1L. Clinical trial information: NCT00700102. [Table: see text]

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