Neoadjuvant therapy

The phase II, multicenter, randomized A021501 trial (NCT02839343) enrolled 126 patients with borderline resectable pancreatic cancer from institutions in the National Clinical Trials Network cooperative groups between 2017 and 2019. Patients were assigned to receive either eight 2-week cycles of modified FOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and 5-FU) (n = 65) or seven 2-week cycles of modified FOLFIRINOX followed by stereotactic body radiotherapy (33 Gy–40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions) (n = 55). Patients without disease progression then underwent surgery followed by four 2-week cycles of adjuvant FOLFOX6 (oxaliplatin, leucovorin, and 5-FU).[12]

The phase II, multicenter, randomized A021501 trial (NCT02839343) enrolled 126 patients with borderline resectable pancreatic cancer from institutions in the National Clinical Trials Network cooperative groups between 2017 and 2019. Patients were assigned to receive either eight 2-week cycles of modified FOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and 5-FU) (n = 65) or seven 2-week cycles of modified FOLFIRINOX followed by stereotactic body radiotherapy (33 Gy–40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions) (n = 55). Patients without disease progression then underwent surgery followed by four 2-week cycles of adjuvant FOLFOX6 (oxaliplatin, leucovorin, and 5-FU).[12]

In the neoadjuvant chemotherapy-alone arm, the median overall survival (OS) was 29.8 months (95% confidence interval [CI], 21.1–36.6) with a 43% microscopically margin-negative (R0) resection rate. This was compared with estimated historical controls of median OS at 18 months.[12][Level of evidence C3]

The phase II, multicenter, randomized A021501 trial (NCT02839343) enrolled 126 patients with borderline resectable pancreatic cancer from institutions in the National Clinical Trials Network cooperative groups between 2017 and 2019. Patients were assigned to receive either eight 2-week cycles of modified FOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and 5-FU) (n = 65) or seven 2-week cycles of modified FOLFIRINOX followed by stereotactic body radiotherapy (33 Gy–40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions) (n = 55). Patients without disease progression then underwent surgery followed by four 2-week cycles of adjuvant FOLFOX6 (oxaliplatin, leucovorin, and 5-FU).[12]

Grade 3 or greater treatment-related adverse events occurred in 57% of patients who received neoadjuvant chemotherapy alone.

The phase II, multicenter, randomized A021501 trial (NCT02839343) enrolled 126 patients with borderline resectable pancreatic cancer from institutions in the National Clinical Trials Network cooperative groups between 2017 and 2019. Patients were assigned to receive either eight 2-week cycles of modified FOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and 5-FU) (n = 65) or seven 2-week cycles of modified FOLFIRINOX followed by stereotactic body radiotherapy (33 Gy–40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions) (n = 55). Patients without disease progression then underwent surgery followed by four 2-week cycles of adjuvant FOLFOX6 (oxaliplatin, leucovorin, and 5-FU).[12]

The neoadjuvant chemotherapy with radiation arm was closed at interim futility analysis because of low R0 resection rates (33%) in the first 30 patients enrolled.

The multicenter phase III PREOPANC trial included 246 patients diagnosed with resectable or borderline resectable pancreatic cancer between 2013 and 2017. Patients at 16 Dutch centers were randomly assigned to receive either diagnostic laparoscopy, neoadjuvant chemoradiation therapy, surgical resection, and four cycles of adjuvant gemcitabine or up-front surgery and six cycles of adjuvant gemcitabine. Neoadjuvant chemoradiation therapy included the following: cycle 1 (21 days) with gemcitabine 1,000 mg/m2 on days 1 and 8; cycle 2 (28 days) with gemcitabine on days 1, 8, and 15 with 15 concurrent fractions of hypofractionated radiation (36 Gy) to the tumor and suspected associated lymph nodes; and cycle 3 (21 days) with gemcitabine on days 1 and 8.[13] The optimal neoadjuvant therapy regimen is unknown, and additional chemotherapy regimens are being evaluated in the following trials: ALLIANCE (NCT04340141), PREOPANC-3 (NCT04927780), PANACHE-01-PRODIGE (NCT02959879), and NorPACT-01 (NCT02919787).

The multicenter phase III PREOPANC trial included 246 patients diagnosed with resectable or borderline resectable pancreatic cancer between 2013 and 2017. Patients at 16 Dutch centers were randomly assigned to receive either diagnostic laparoscopy, neoadjuvant chemoradiation therapy, surgical resection, and four cycles of adjuvant gemcitabine or up-front surgery and six cycles of adjuvant gemcitabine. Neoadjuvant chemoradiation therapy included the following: cycle 1 (21 days) with gemcitabine 1,000 mg/m2 on days 1 and 8; cycle 2 (28 days) with gemcitabine on days 1, 8, and 15 with 15 concurrent fractions of hypofractionated radiation (36 Gy) to the tumor and suspected associated lymph nodes; and cycle 3 (21 days) with gemcitabine on days 1 and 8.[13] The optimal neoadjuvant therapy regimen is unknown, and additional chemotherapy regimens are being evaluated in the following trials: ALLIANCE (NCT04340141), PREOPANC-3 (NCT04927780), PANACHE-01-PRODIGE (NCT02959879), and NorPACT-01 (NCT02919787).

The 5-year OS rate was 20.5% (95% CI, 14.2%–29.8%) for patients who received neoadjuvant chemoradiation therapy and 6.5% (95% CI, 3.1%–13.7%) for patients who received up-front surgery (hazard ratio [HR], 0.73; 95% CI, 0.56–0.96; P = .025).[13][Level of evidence A1]

The multicenter phase III PREOPANC trial included 246 patients diagnosed with resectable or borderline resectable pancreatic cancer between 2013 and 2017. Patients at 16 Dutch centers were randomly assigned to receive either diagnostic laparoscopy, neoadjuvant chemoradiation therapy, surgical resection, and four cycles of adjuvant gemcitabine or up-front surgery and six cycles of adjuvant gemcitabine. Neoadjuvant chemoradiation therapy included the following: cycle 1 (21 days) with gemcitabine 1,000 mg/m2 on days 1 and 8; cycle 2 (28 days) with gemcitabine on days 1, 8, and 15 with 15 concurrent fractions of hypofractionated radiation (36 Gy) to the tumor and suspected associated lymph nodes; and cycle 3 (21 days) with gemcitabine on days 1 and 8.[13] The optimal neoadjuvant therapy regimen is unknown, and additional chemotherapy regimens are being evaluated in the following trials: ALLIANCE (NCT04340141), PREOPANC-3 (NCT04927780), PANACHE-01-PRODIGE (NCT02959879), and NorPACT-01 (NCT02919787).

The median OS was 15.7 months in the neoadjuvant chemoradiation therapy group and 14.3 months in the up-front surgery group.

The multicenter phase III PREOPANC trial included 246 patients diagnosed with resectable or borderline resectable pancreatic cancer between 2013 and 2017. Patients at 16 Dutch centers were randomly assigned to receive either diagnostic laparoscopy, neoadjuvant chemoradiation therapy, surgical resection, and four cycles of adjuvant gemcitabine or up-front surgery and six cycles of adjuvant gemcitabine. Neoadjuvant chemoradiation therapy included the following: cycle 1 (21 days) with gemcitabine 1,000 mg/m2 on days 1 and 8; cycle 2 (28 days) with gemcitabine on days 1, 8, and 15 with 15 concurrent fractions of hypofractionated radiation (36 Gy) to the tumor and suspected associated lymph nodes; and cycle 3 (21 days) with gemcitabine on days 1 and 8.[13] The optimal neoadjuvant therapy regimen is unknown, and additional chemotherapy regimens are being evaluated in the following trials: ALLIANCE (NCT04340141), PREOPANC-3 (NCT04927780), PANACHE-01-PRODIGE (NCT02959879), and NorPACT-01 (NCT02919787).

In the intention-to-treat arm, 61% of patients who received neoadjuvant chemoradiation therapy underwent resection, resulting in R0 resection for 41% of patients and node-negative disease for 65% of patients. The resection rate was 72% in the up-front surgery arm, resulting in R0 resection in 28% of patients and node-negative disease in 18% of patients.