Among patients with advanced pancreatic cancer who receive first-line palliative chemotherapy within a universal health care system, drug funding decisions are associated with increased use of new treatments over time as well as improved survival, according to a study in JAMA Network Open.

Investigators aimed to evaluate changes in patient survival for advanced pancreatic cancer associated with sequential drug funding approvals and to determine whether there are patient populations for whom gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) are associated with survival benefits.

The population-based, retrospective cohort study enrolled patients with locally advanced and unresectable or metastatic pancreatic cancer in Ontario, Canada, from November 7, 2008, to December 31, 2018. Eligible participants had received at least 1 dose of first-line gemcitabine, GEMNAB, or FOLFIRINOX. The patients were identified in the New Drug Funding Program database.


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A total of 5465 patients were included. Their median age was 66.9 (range, 27.8-93.4) years, 2447 (45%) were women, and 4777 (87%) were urban-dwelling residents. Among the cohort, 878 patients (16%) had previous pancreatic resection, and 328 (6%) had prior adjuvant single-agent gemcitabine chemotherapy.

In the period when only gemcitabine and FOLFIRINOX were funded for treatment of pancreatic cancer, 51% (958 of 1887) of patients received gemcitabine and 49% (929 of 1887) received FOLFIRINOX. An immediate decrease occurred in the use of single-agent gemcitabine when GEMNAB was funded. When all 3 agents were funded, 9% (206 of 2347) of patients received gemcitabine, 44% (1034 of 2347) received FOLFIRINOX, and 47% (1107 of 2347) received GEMNAB.

After a median follow-up of 209 (IQR, 94-406) days, the median overall survival increased from 5.6 months (95% CI, 5.1-6.0 months) in 2008 to 2011, to 6.9 months (95% CI, 6.4-7.4 months) in 2011 to 2015, and to 7.7 months (95% CI, 7.3-8.2 months) in 2015 to 2018.

FOLFIRINOX was associated with better overall survival vs GEMNAB in adjusted models with inverse probability of treatment (IPT) weighting (weighted adjusted hazard ratio [aHR], 0.78; 95% CI, 0.73-0.83) and without IPT weighting (aHR 0.78; 95% CI, 0.71-0.87).

Patients treated with GEMNAB from 2015 to 2018 had better overall survival than those who were treated with gemcitabine from 2011 to 2015 (aHR, 0.86 [95% CI, 0.78-0.94]; IPT-weighted aHR, 0.86 [95% CI, 0.80-0.92]; matched aHR, 0.78 [95% CI, 0.67-0.90]).

Among several study limitations, the analysis was limited to all incident cases of advanced pancreatic cancer treated with first-line chemotherapy, and information on the use of second-line chemotherapies was unavailable. Additionally, the cohort predates funding approval for FOLFIRINOX, gemcitabine, and capecitabine in the adjuvant setting. Finally, selection bias may have affected the observed treatment effect estimates.

“These findings suggest that drug-funding reimbursement decisions are associated with improvements in survival for patients with advanced pancreatic cancer,” the researchers commented.

Disclosure: One of the study authors declared affiliations with a pharmaceutical company. Please see the original reference for a full list of authors’ disclosures.

Reference

Raphael MJ, Raskin W, Habbous S, et al. The association of drug-funding reimbursement with survival outcomes and use of new systemic therapies among patients with advanced pancreatic cancer. JAMA Netw Open. 2021;4(11):e2133388. doi: 10.1001/jamanetworkopen.2021.33388