Post-induction chemoradiotherapy (CRT) improved resectability, when compared with chemotherapy alone, in patients with unresectable, locally advanced pancreatic cancer, according to research presented at the 2022 ASCO Annual Meeting.
These first results from the CONKO-007 trial revealed that R0 and circumferential resection margin (CRM)-negative resection rates were higher with CRT. However, overall survival (OS) outcomes were similar with CRT and chemotherapy alone.
The phase 3 CONKO-007 trial (ClinicalTrials.gov Identifier: NCT01827553) was designed to compare CRT with chemotherapy alone for patients who had already received 3 months of induction chemotherapy (3 cycles of gemcitabine [1000 mg/m² on days 1, 8, and 15, every 4 weeks] or 6 cycles of FOLFIRINOX [every 2 weeks]).
The patients without progression after induction were randomly assigned to either continue chemotherapy for another 3 months or receive CRT (cumulative dose of 50.4 Gy, single dose of 1.8 Gy plus gemcitabine at 300 mg/m² weekly, followed by 1 cycle of gemcitabine at 1000 mg/m² on days 1, 8, and 15).
A total of 525 patients were enrolled between April 2013 and February 2021 at 47 sites. Most patients (n=402) received induction with FOLFIRINOX, and 93 received gemcitabine. Once induction was completed, 190 patients were excluded due to progression or toxicity. Therefore, 169 patients went on to receive CRT, and 167 went on to receive chemotherapy alone.
Hematologic toxicities, specifically leukopenia and thrombocytopenia, were seen more frequently in the CRT arm. The researchers noted that these adverse events were well managed, and therapy-related deaths were equally distributed between the 2 treatment arms. Non-hematologic toxicities were also comparable between the treatment arms.
In looking at patients who underwent resection, R0 resections were significantly higher in patients who received CRT than in those who received chemotherapy alone (69% vs 50%, respectively; P =.0418). CRM-negative resection was more frequently observed in the CRT arm than in the chemotherapy-alone arm (47% vs 25%, respectively; P =.0147).
The pathologic complete remission rate was higher in the CRT arm than in the chemotherapy arm (18% vs 2%; P =.0043). The findings trended similarly when data from all randomly assigned patients were included.
The effect of CRT on resectability did not translate into significant improvements in progression-free survival (PFS) or overall survival (OS). In all randomized patients, the median PFS was 8 months in the chemotherapy arm and 9 months in the CRT arm (hazard ratio [HR], 0.976; P =.835). The median OS was 15 months in both arms (HR, 0.975; P =.713).
There was a significant improvement in OS for patients who underwent surgery, compared with those who did not. The median OS was 19 months and 14 months, respectively (HR, 0.573; P <.001).
Similarly, there were significant improvements in OS for patients who had R0 and CRM-negative resections, compared with those who did not. The median OS was 26 months in patients with R0 resection and 17 months in those with R1 resection (HR, 0.2155; P =.006). The median OS was 36 months in patients with CRM-negative resection and 18 months in those with CRM-positive resection (HR, 0.2293; P =.002).
According to the researchers, these results suggest that R0 and CRM-negative resections are important for long-term survival in this patient population, and CRT plus surgery after induction chemotherapy is feasible.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Fietkau R, Ghadimi M, Grützmann R, et al. Randomized phase III trial of induction chemotherapy followed by chemoradiotherapy or chemotherapy alone for nonresectable locally advanced pancreatic cancer: First results of the CONKO-007 trial. Presented at ASCO 2022. June 3-7, 2022. Abstract 4008.