Preoperative chemoradiotherapy failed to boost overall survival in pancreatic cancer

Preoperative chemoradiotherapy failed to improve overall survival among patients with resectable or borderline resectable pancreatic cancer, according to findings from a phase 3 trial.

On the other hand, preoperative chemoradiotherapy improved disease-free survival, locoregional failure-free interval, and other secondary endpoints, according to study author Eva Versteijne, MD, of the University of Amsterdam, and colleagues. Their findings were published in the Journal of Clinical Oncology.

The randomized, phase 3 study included 246 patients with borderline or resectable pancreatic ductal adenocarcinoma without distant metastases. Patients were randomized to receive preoperative chemoradiotherapy (n = 119) or immediate surgery (n = 127).

Patients in the preoperative chemoradiotherapy arm received three courses of gemcitabine at 1,000 mg/m², combined with 15 fractions of radiotherapy at 2.4 Gy during the second course. Explorative laparotomy with subsequent resection followed, in addition to four 4-week cycles of adjuvant gemcitabine at 1,000 mg/m². Following resection in the immediate surgery arm, patients received six 4-week cycles of adjuvant gemcitabine at the same dose.

The primary outcome was median overall survival in the intention-to-treat population. The median overall survival was 16.0 months in the preoperative chemoradiotherapy arm and 14.3 months in the immediate surgery arm (hazard ratio, 0.78; P = .096).

Secondary outcomes included disease-free survival, resection rate, R0 resection rate, and locoregional failure-free interval, among others.

The resection rate was 61% in the preoperative chemoradiotherapy arm and 72% in the immediate surgery arm (odds ratio, 0.58; P = .058). The R0 resection rates were 71% and 40%, respectively (OR, 3.61; P less than .001).

The median disease-free survival was 8.1 months in the preoperative chemoradiotherapy arm and 7.7 months in the immediate surgery arm (HR, 0.73; P = .032). The median locoregional failure-free interval was not reached and 13.4 months, respectively (HR, 0.56; P = .0034). The rate of serious adverse events was 52% and 41%, respectively (OR, 1.57; P = .096).

“Preoperative chemoradiotherapy was associated with significantly better [disease-free survival] and [locoregional failure-free interval] as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion,” the researchers noted.

They acknowledged that some findings, particularly the median overall survival in patients assigned to immediate surgery, require further investigation, as these data suggest the trial may have been underpowered.

“The consistent benefits for most secondary endpoints and the better compliance with preoperative chemoradiotherapy compared with postoperative adjuvant chemotherapy suggest superiority of the neoadjuvant approach,” the researchers concluded.

The study was funded by the Dutch Cancer Society. The authors disclosed financial affiliations with Bristol-Myers Squibb, Eisai, Ipsen, Merck Serono, and several other companies.

SOURCE: Versteijne E et al. J Clin Oncol. 2020 Feb 27. doi: 10.1200/JCO.19.02274.

Preoperative chemoradiotherapy failed to improve overall survival among patients with resectable or borderline resectable pancreatic cancer, according to findings from a phase 3 trial.

On the other hand, preoperative chemoradiotherapy improved disease-free survival, locoregional failure-free interval, and other secondary endpoints, according to study author Eva Versteijne, MD, of the University of Amsterdam, and colleagues. Their findings were published in the Journal of Clinical Oncology.

The randomized, phase 3 study included 246 patients with borderline or resectable pancreatic ductal adenocarcinoma without distant metastases. Patients were randomized to receive preoperative chemoradiotherapy (n = 119) or immediate surgery (n = 127).

Patients in the preoperative chemoradiotherapy arm received three courses of gemcitabine at 1,000 mg/m², combined with 15 fractions of radiotherapy at 2.4 Gy during the second course. Explorative laparotomy with subsequent resection followed, in addition to four 4-week cycles of adjuvant gemcitabine at 1,000 mg/m². Following resection in the immediate surgery arm, patients received six 4-week cycles of adjuvant gemcitabine at the same dose.

The primary outcome was median overall survival in the intention-to-treat population. The median overall survival was 16.0 months in the preoperative chemoradiotherapy arm and 14.3 months in the immediate surgery arm (hazard ratio, 0.78; P = .096).

Secondary outcomes included disease-free survival, resection rate, R0 resection rate, and locoregional failure-free interval, among others.

The resection rate was 61% in the preoperative chemoradiotherapy arm and 72% in the immediate surgery arm (odds ratio, 0.58; P = .058). The R0 resection rates were 71% and 40%, respectively (OR, 3.61; P less than .001).

The median disease-free survival was 8.1 months in the preoperative chemoradiotherapy arm and 7.7 months in the immediate surgery arm (HR, 0.73; P = .032). The median locoregional failure-free interval was not reached and 13.4 months, respectively (HR, 0.56; P = .0034). The rate of serious adverse events was 52% and 41%, respectively (OR, 1.57; P = .096).

“Preoperative chemoradiotherapy was associated with significantly better [disease-free survival] and [locoregional failure-free interval] as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion,” the researchers noted.

They acknowledged that some findings, particularly the median overall survival in patients assigned to immediate surgery, require further investigation, as these data suggest the trial may have been underpowered.

“The consistent benefits for most secondary endpoints and the better compliance with preoperative chemoradiotherapy compared with postoperative adjuvant chemotherapy suggest superiority of the neoadjuvant approach,” the researchers concluded.

The study was funded by the Dutch Cancer Society. The authors disclosed financial affiliations with Bristol-Myers Squibb, Eisai, Ipsen, Merck Serono, and several other companies.

SOURCE: Versteijne E et al. J Clin Oncol. 2020 Feb 27. doi: 10.1200/JCO.19.02274.

Preoperative chemoradiotherapy failed to improve overall survival among patients with resectable or borderline resectable pancreatic cancer, according to findings from a phase 3 trial.

On the other hand, preoperative chemoradiotherapy improved disease-free survival, locoregional failure-free interval, and other secondary endpoints, according to study author Eva Versteijne, MD, of the University of Amsterdam, and colleagues. Their findings were published in the Journal of Clinical Oncology.

The randomized, phase 3 study included 246 patients with borderline or resectable pancreatic ductal adenocarcinoma without distant metastases. Patients were randomized to receive preoperative chemoradiotherapy (n = 119) or immediate surgery (n = 127).

Patients in the preoperative chemoradiotherapy arm received three courses of gemcitabine at 1,000 mg/m², combined with 15 fractions of radiotherapy at 2.4 Gy during the second course. Explorative laparotomy with subsequent resection followed, in addition to four 4-week cycles of adjuvant gemcitabine at 1,000 mg/m². Following resection in the immediate surgery arm, patients received six 4-week cycles of adjuvant gemcitabine at the same dose.

The primary outcome was median overall survival in the intention-to-treat population. The median overall survival was 16.0 months in the preoperative chemoradiotherapy arm and 14.3 months in the immediate surgery arm (hazard ratio, 0.78; P = .096).

Secondary outcomes included disease-free survival, resection rate, R0 resection rate, and locoregional failure-free interval, among others.

The resection rate was 61% in the preoperative chemoradiotherapy arm and 72% in the immediate surgery arm (odds ratio, 0.58; P = .058). The R0 resection rates were 71% and 40%, respectively (OR, 3.61; P less than .001).

The median disease-free survival was 8.1 months in the preoperative chemoradiotherapy arm and 7.7 months in the immediate surgery arm (HR, 0.73; P = .032). The median locoregional failure-free interval was not reached and 13.4 months, respectively (HR, 0.56; P = .0034). The rate of serious adverse events was 52% and 41%, respectively (OR, 1.57; P = .096).

“Preoperative chemoradiotherapy was associated with significantly better [disease-free survival] and [locoregional failure-free interval] as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion,” the researchers noted.

They acknowledged that some findings, particularly the median overall survival in patients assigned to immediate surgery, require further investigation, as these data suggest the trial may have been underpowered.

“The consistent benefits for most secondary endpoints and the better compliance with preoperative chemoradiotherapy compared with postoperative adjuvant chemotherapy suggest superiority of the neoadjuvant approach,” the researchers concluded.

The study was funded by the Dutch Cancer Society. The authors disclosed financial affiliations with Bristol-Myers Squibb, Eisai, Ipsen, Merck Serono, and several other companies.

SOURCE: Versteijne E et al. J Clin Oncol. 2020 Feb 27. doi: 10.1200/JCO.19.02274.