Adjuvant Chemotherapy Yields Improved Overall Survival in PDAC Population Aged 80 Years or Older

Patients aged 80 years or older who received adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) following pancreaticoduodenectomy had a longer median overall survival (OS) despite being administered to fewer 50% of patients, according to a study published in JAMA Oncology.

Investigators reported a median OS of 17.2 months (95% CI, 16.1-19.0) among those who received adjuvant chemotherapy compared with 12.7 months (95% CI, 11.8-13.6) for those who did not. A decreased hazard of death was associated with adjuvant chemotherapy (HR, 0.72; 95% CI, 0.65-0.79; P <.01), female sex (HR, 0.88; 95% CI, 0.80-0.96; P<.001), and surgery from 2011 or later (HR, 0.90; 95% CI, 0.82-0.99; P = .02). An increased hazard of death was observed with higher pathologic stage such as stage II (HR, 1.68; 95% CI, 1.43-1.97; P <.001) or stage III (HR, 2.39; 95% CI, 1.88-3.04; P <.001), positive surgical margins (HR, 1.49; 95% CI, 1.34-1.65; P <.001), length of stay longer than 10 days (HR, 1.17; 95% CI, 1.07-1.28; P <.001), and receiving oncologic care at nonacademic facilities such as the Community Cancer Program (HR, 1.20; 95% CI, 1.07-1.35; P <.001) or Integrated Network Cancer Program (HR, 1.25; 95% CI, 1.07-1.46; P<.001). 

“In this cohort study of patients older than 80 years who underwent pancreaticoduodenectomy for pancreatic cancer, findings suggest that age alone should not preclude patients from curative intent with surgery and chemotherapy. It is imperative that we shift our treatment paradigm from one that reserves curative intent for a minority of patients 80 years and older to one that is centered on evidence-based criteria and considers individual risk and preference, beyond chronologic age,” the study investigators wrote.

The study took place between 2004 and 2016 and included 2569 patients who were aged 80 years or older. Patients underwent a pancreaticoduodenectomy for PDAC, and 1217 received adjuvant chemotherapy. When comparing rates from 2004 to 2016, investigators noted an increase in adjuvant chemotherapy among older patients who underwent a pancreaticoduodenectomy. Of the patients who received adjuvant chemotherapy, 906 were given single-agent chemotherapy, and 214 underwent treatment with a multiagent chemotherapy regimen. Ninety-seven patients received unknown regimens.

Those who received adjuvant chemotherapy compared with those who did not were less likely to be female (51.4% vs 59.3%; P <.001); had a higher pathological stage including stage IIB (68.1% vs 56.7%; P <.001) and stage III (5.3% vs 4.2%; P <.001); were more likely to have positive surgical margins (24.2% vs 20.1%; P = .03), less likely to have an index surgical admission greater than 10 days (31.7% vs 51.6%; P <.001), and more likely receive treatment in the Mid-Atlantic region (24.4% vs 21.1%; P <.001).

The median number of days from diagnosis to start of chemotherapy was 82 (95% CI, 79-84), with 532 patients initiating chemotherapy 90 days following diagnosis. After a median follow-up of 14.4 months, the median OS was 15.0 months (95% CI, 14.1-15.7) in the adjuvant chemotherapy cohort. Moreover, the 5-year OS rate for those who received adjuvant chemotherapy increased from 10.9% to 15.2% compared with those who did not (P <.001).

For those in the propensity-matched cohort (n = 1868), 934 patients received adjuvant chemotherapy. After a median follow-up of 14.6 months, investigators reported a median OS of 15.3 months (95% CI, 14.2-16.1). Treatment with adjuvant chemotherapy was found to be associated with a longer median OS (17.2; 95% CI, 16.0-19.2) vs patients who were not treated (12.8; 95% CI, 11.7-14.1; P <.001).

The sensitivity analysis indicated that a decreased hazard of death and a longer median OS was observed for those with node-negative, margin-negative, clinically complex, node-positive, and margin-positive disease who received adjuvant chemotherapy. At about 7 months, the chemotherapy and no-chemotherapy curves converged, but did not cross. The benefit of chemotherapy was present, but with a reduced magnitude.

Treatment with chemotherapy before 7 months resulted in a 51% reduction in risk of death (HR, 0.49; P <.001) compared with a 16% reduction in the risk of death when used 7 months after (HR, 0.84; P = .002).

Reference

Mehtsun WT, McCleary NJ, Maduekwe UN, Wolpin BM, Schrag D, Wang J. Patterns of adjuvant chemotherapy use and association with survival in adults 80 years and older with pancreatic adenocarcinoma. JAMA Oncol. 2021;e215407. doi:10.1001/jamaoncol.2021.5407