Posters dealing with nal-IRI

Andrea Wang-Gillam, et al.

Dose modifications of liposomal irinotecan (nal-IRI) + 5-fluorouracil/leucovorin (5-FU/LV) in NAPOLI-1: Impact on efficacy.

Conclusions: Dose modifications in the nal-IRI+5-FU/LV arm did not significantly impact OS compared with those who did not need a dose modification, and OS remained greater than in 5-FU/LV-treated patients. This suggests that appropriate dose modification of nal-IRI+5-FU/LV for AEs may not adversely affect outcomes. Clinical trial information: NCT01494506

J Clin Oncol 36, 2018 (suppl 4S; abstr 388)


Annette K Larsen, et al.

Influence of liposomal irinotecan (nal-IRI) and non-liposomal irinotecan, alone and in combination, on tumor growth and angiogenesis in colorectal cancer (CRC) models.

Conclusions: Our results suggest that both irinotecan HCl and nal-IRI can counteract the hypoxia-mediated increase of HIF1αin vivo as previously reported in vitro. Furthermore, the combination of the two formulations demonstrated significant efficacy benefits. A combination of irinotecan HCl and nal-IRI merits further clinical investigation.

J Clin Oncol 36, 2018 (suppl 4S; abstr 711)


Shannon C. Leonard, et al.

Deposition characteristics and resulting DNA damage patterns of liposomal irinotecan (nal-IRI) in pancreatic cancer xenografts.

Conclusions: nal-IRI improves tumoral deposition of its payload in pancreatic tumor models. Liposomal deposition in tumors is heterogeneous and restricted to perivascular areas and is mainly observed in macrophages/non-tumor cells. DNA damage with nal-IRI treatment occurs predominantly in tumor cells outside of the liposomal deposition area. The results therefore suggest sufficient intratumoral levels of the SN-38 active metabolite, possibly after payload release by stromal macrophages and concomitant conversion. nal-IRI demonstrates a greater reduction in tumor growth in a variety of pancreatic tumor models at a 5-fold lesser dose than irinotecan. The effects of repeated dosing cycles should be explored.

J Clin Oncol 36, 2018 (suppl 4S; abstr 335)


Teresa Mercade Macarulla, et al.

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.

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

J Clin Oncol 36, 2018 (suppl 4S; abstr 410)


Jens T. Siveke, et al.

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.

Conclusions:

Treatment with nal-IRI in combination with 5-FU/LV in the NAPOLI-1 study has demonstrated clinical benefit (45% median OS increase) and predictable and manageable toxicity in patients with mPDAC previously treated with gemcitabine-based therapy.4

The results of this post-hoc subgroup analysis suggest that the presence of lesions in the liver and, to some degree, the number of measurable metastatic lesions at baseline may be useful prognostic indicators for mortality and disease progression outcomes, regardless of treatment received.

Treatment benefit with nal-IRI+5-FU/LV vs. 5-FU/LV alone was observed in most baseline measurable metastatic lesion number and all lesion location subgroups.

– However, the differences did not reach statistical significance in all groups, and firm conclusions are precluded by small patient numbers in many subgroups.

Overall, these data support the use of nal-IRI+5-FU/LV in patients with mPDAC previously treated with gemcitabine-based therapy, regardless of the number of measurable metastatic lesions or location of lesions at baseline.

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

J Clin Oncol 36, 2018 (suppl 4S; abstr 460)


Andrea Wang-Gillam, et al.

Nomogram for predicting overall survival (OS) in patients (pts) treated with liposomal irinotecan (nal-IRI) ± 5-fluorouracil/leucovorin (5-FU/LV) in metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy in NAPOLI-1.

Conclusions:

  • Through univariable and multivariable analyses, 8 baseline patient and disease characteristics from patients in the NAPOLI-1 clinical trial were identified that formed the basis of a nomogram to assist in predicting the OS of patients treated with nal-IRI+5-FU/LV.

  • Treatment with nal-IRI+5-FU/LV was identified as an important factor in the nomogram.

  • This nomogram distinguishes between risk groups and may aid in clinical decision making.

In NAPOLI-1, predictors of OS were nal-IRI+5-FU/LV treatment, KPS, NLR, albumin level, baseline CA19-9, stage 4 at diagnosis, BMI, and presence of liver metastasis. The nomogram, which will distinguish between risk groups and may aid in clinical decision making, will be presented in the poster. Clinical trial information: NCT01494506

J Clin Oncol 36, 2018 (suppl 4S; abstr 459)

NOMOGRAM

Teresa Mercade Macarulla, et al.

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.

Conclusions:

 

Treatment with nal-IRI in combination with 5-FU/LV in the NAPOLI-1 study has demonstrated clinical benefit (45% median OS increase) and predictable and manageable toxicity in patients with mPDAC previously treated with gemcitabine-based therapy.4

The results of this post-hoc subgroup analysis suggest that:

  • –  Higher baseline pain intensity and analgesic use may be useful prognostic parameters for patients with metastatic pancreatic cancer previously treated with gemcitabine-based therapy.

  • –  Treatment benefit was maintained in patients with high and low BPI and BAU across most subgroups who received nal-IRI+5-FU/LV compared with patients who received 5-FU/LV alone.

o However, the differences did not reach statistical significance in all groups, and firm conclusions are precluded by small patient numbers in many subgroups.

– The safety profile for nal-IRI+5-FU/LV within BPI and BAU subgroups was consistent with the overall NAPOLI-1 population.
o There were no notable differences between high and low BPI and BAU subgroups, except for a higher incidence of abdominal pain in the BPI and BAU <0 and <median subgroups.
o Drug discontinuations due to TEAEs were numerically higher in higher pain and analgesic use subgroups.

Overall, this post-hoc analysis supports the use of nal-IRI+5-FU/LV in patients with mPDAC previously treated with gemcitabine-based therapy who have either high or low BPI and BAU.

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

J Clin Oncol 36, 2018 (suppl 4S; abstr 379)