Real-World Efficacy Data Reveals OS Boost With Liposomal Irinotecan Plus 5-FU for Metastatic PDAC

A real-world analysis revealed that increased treatment duration with the combination of liposomal irinotecan (Onivyde) plus 5-fluorouracil (5-FU)/leucovorin led to higher rates of overall survival at 1 year in patients with metastatic pancreatic ductal adenocarcinoma (PDAC), according to a presentation at the 2021 ASCO Gastrointestinal Cancers Symposium.¹

All patients included in the retrospective analysis had a 1-year OS rate of 17.2% (95% CI, 14.3%-20.7%). Moreover, those who had received the regimen in the frontline setting achieved a 1-year OS rate of 31.5% (95% CI, 22.1%-41.3%), while those who received it in the second-line setting had a 1-year OS rate of 16.4% (95% CI, 12.2-21.1). Patients who received the regimen as a third-line treatment experienced a 1-year OS rate of 12.2% (95% CI, 7.5%-18.0%).

Additionally, those who received at least 2 cycles of liposomal irinotecan had a 1-year OS rate of 20.4% (95% CI, 16.8%-24.2%). Patients who were administered at least 4 cycles of liposomal irinotecan had an estimated 1-year OS rate of 29.1% (95% CI, 24.0%-34.3%), while those who received at least 8 cycles had an estimated rate of 47.9% (95% CI, 39.7%-55.7%).

Although patients with pancreatic cancer have a poor 5-year relative survival rate of just 9%, those with metastatic disease have an even lower rate of 2.9%.^2,3 The combination of liposomal irinotecan and 5-FU received approval from the FDA in October 2015 for use in patients with metastatic pancreatic cancer who had progressed on gemcitabine-based chemotherapy.

The regulatory decision was based on results from the phase 3 NAPOLI-1 trial (NCT01494506), which showed that 25% of patients (n = 29) with metastatic PDAC who had previously received gemcitabine-based therapy were alive for 1 year or more following treatment with the regimen. Most recently, in June 2020, the regimen was granted a fast track designation by the FDA for patients with previously untreated, unresectable, locally advanced or metastatic PDAC.^4,5

For the retrospective descriptive analysis presented at the 2021 Gastrointestinal Cancers Symposium, investigators set out to further evaluate the 1-year survival of patients with metastatic PDAC who received treatment with liposomal irinotecan plus 5-FU in the real-world setting. To do this, investigators utilized the Flatiron Health longitudinal database, which houses de-identified, patient-level structured and unstructured information from over 280 cancer clinics.

Patients aged 18 years or older at the time of treatment initiation, who had received the regimen in the metastatic setting and who had 1 or more recorded activities following the start of their treatment, were included in the analysis. Investigators identified and looked at data from these patients who received liposomal irinotecan between November 1, 2015 and July 31, 2020.

Investigators identified a total of 669 patients with metastatic PDAC who had received the regimen between November 1, 2015 and July 31, 2020 to include in the analysis. Patients had a median age of 69 years at the time of treatment initiation (range, 62-75) and the majority were male (53%). Moreover, over half of all patients, or 57%, had an ECOG performance status of 0-1. Additionally, 47.5% of patients received treatment with the regimen in the second-line metastatic setting. In total, 16.3% (n = 109) of patients had received 1 prior line of therapy, 47.5% (n = 318) received 2 prior lines, and 36.2% (n = 242) received 3 or more prior lines.

Patients enrolled on the trial received an average of 6.2 cycles of treatment (SD, 7.5), with a median of 4 cycles of therapy received in the overall patient population. Patients who were receiving the regimen as first-line treatment received a median of 5 cycles of liposomal irinotecan plus 5-FU, those who had received it in the second-line setting received a median of 4 cycles, and those who received it in the third-line setting received a median of 3 cycles.

When compared with the registrational phase 3 NAPOLI-1 study, the patients included in this analysis were older and had received more prior lines of therapy; they also had a worse performance status. However, patients in both the study and analysis received a similar number of treatment cycles, at a median of 4.

Of the patients who received at least 4 cycles of the regimen, 1-year OS was found to be similar between those in the analysis and those in the intent-to-treat and per protocol-treated populations examined in the NAPOLI-1 trial, at 29%, 25%, and 34%, respectively.

Investigators concluded that further studies are needed to further understand and identify predictors of long-term survival in patients with metastatic PDAC.

References:

1. Kim G, Cockrum P, Surinach A, et al. Real-world one-year overall survival among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan in the NAPOLI-1 based regimen. Poster presented at: 2020 Gastrointestinal Cancers Symposium; January 15-17, 2021; Virtual. Accessed January 15, 2021. https://bit.ly/35JdR6y.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1)7-30. doi:10.3322/caac.21590.
3. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2017. National Cancer Institute. April 2020. Accessed January 15, 2021. http://bit.ly/38LL8zW.
4. Ipsen receives FDA fast track designation for liposomal irinotecan (ONIVYDE®) as a first-line combination treatment for metastatic pancreatic cancer. News release. Ipsen. June 17, 2020. Accessed January 15, 2021. https://bit.ly/2BkyKbG.
5. Chen L-T, Von Hoff DD, Li C-P, et al. Expanded analyses of NAPOLI-1: phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy. J Clin Oncol. 2015;33(suppl 3):234. doi:10.1200/jco.2015.33.3_suppl.234