Nab-paclitaxel plus CRT on par with standard treatment in pancreatic cancer

Concurrent chemoradiotherapy (CRT) with nab-paclitaxel for the treatment of borderline resectable or unresectable pancreatic cancer is well tolerated and contributes to fewer incidence of local failure and higher conversion to resectability, both of which are statistically nonsignificant, a study has shown.

“Nab-paclitaxel given concurrently with radiotherapy seems to be fairly equivalent to standard CRT and may provide clinicians another reasonable regime to use when 5-fluorouracil or gemcitabine-based regimens cannot be administered, though further evaluation of its safety in clinical trials are necessary,” the researchers said.

Fifty patients with borderline resectable or unresectable pancreatic adenocarcinoma from 2014 to 2017 were grouped to receive concurrent nab-paclitaxel (100 to 125 mg/m² weekly) CRT (median, 2.1 Gy fraction size and 52.5 Gy total) or standard CRT (median, 1.8 Gy fraction size, 54.5 Gy total). Toxicity was the primary endpoint, while local failure and conversion to resectability were secondary ones.

The researchers then made comparisons using rank-sum or Fisher exact test and calculated the cumulative incidence of local failure using multivariable competing risk regression.

Of the patients, 28 received nab-paclitaxel CRT and 22 standard CRT; majority of the patients (88 percent) had unresectable disease. The median follow-up was 18 months. The median duration of chemotherapy before concurrent CRT was 1.9 months in the nab-paclitaxel group and 2.3 months in the standard CRT group (p=0.337), while radiotherapy dose was 52.5 Gy (range, 52.5–59.4) and 54.5 Gy (range, 45.0–59.4), respectively. [Am J Clin Oncol 2021;44:469-474]

No grade ≥2 toxicities reached statistical significance. Patients in the nab-paclitaxel CRT group had a lower incidence of local failure (hazard ratio, 0.91, 95 percent confidence interval, 0.27–3.03; p=0.536), but it was not statistically significant. In addition, more patients in the nab-paclitaxel CRT group underwent surgery (9/28 vs 3/22 in the standard CRT group; p=0.186); six of which (25 percent) in the nab-paclitaxel group and two (10 percent) in the standard CRT group were unresectable at first.

“Surgical resection is generally considered the only curative intervention for pancreatic ductal adenocarcinoma, and there is a clear survival benefit for initially resectable patients,” the researchers said. [HPB (Oxford) 2006;8:346-351; Ann Gastroenterol 2013;26:346-352; World J Gastroenterol 2015;21:262-268]

“In borderline resectable or unresectable disease, data supports a survival benefit when an R0 resection can be achieved,” they added. [PLoS Med 2010;7:e1000267; Surgery 2014;155:977-988]

The current study was limited by heterogeneity in the chemotherapy type and duration before CRT between groups, small number of patients, toxicity data collected in a prospective setting, and selection bias. In addition, those receiving concurrent gemcitabine in the standard CRT group were the minority, and such treatment had demonstrated positive results in unresectable patients in terms of local control and conversion to resectable disease. [Int J Radiat Oncol Biol Phys 2012;84:1166-1171]

“These limitations notwithstanding, we demonstrate that concurrent CRT with nab-paclitaxel was well-tolerated, allowed more patients to undergo resection, and resulted in pathologic complete responses,” the researchers said.