Randomized phase III trial of induction chemotherapy followed by chemoradiotherapy or chemotherapy alone for non-resectable locally advanced pancreatic cancer: First results of the CONKO-007 trial

Introduction Chemotherapy (CT) is the standard of care in non-resectable locally advanced pancreatic cancer.

Aim The CONKO-007 trial investigated the role of sequential CT and chemoradiotherapy (CRT).

Methods In this randomized multicenter phase III trialresectability was judged by an independent surgical board. Patients (pts) received induction chemotherapy (IC) for 3months (3 cycles gemcitabine (Gem, 1000mg/m² d1, 8, 15, q4w) or FOLFIRINOX (6 cycles, q2w)). After IC pts without progression were randomized to either continuing CT for another 3 months or receiving CRT (cumulative dose of 50.4Gy, single dose 1.8Gy+Gem 300mg/m² weekly, followed by 1 cycle of Gem 1000mg/m² at d1, 8, 15). The primary endpoint of the study was overall survival (OS) since thebeginning of IC. A total number of 830 pts should be enrolledand 590 pts randomized. Due to delayed patient accrual the primary endpoint was changed to R0 resection rate resulting inan estimated sample size of 525 pts ([Tab. 1]).

Tab. 1 

	CT	CRT	p
total (n)	167	169
surgery, n (%)	60 (36)	62 (37)	0.910
R0, n (%)	30/60 (50)	43/62 (69)	0.042
R1, n (%)	16/60 (27)	5/62 (8)	0.008
CRM–, n (%)	15/42 (36)	29/40 (73)	<0.001
ypN0 n (%)	23/45 (51)	35/47 (74)	0.030
pCR, n (%)	1/167 (0.6)	11/169 (7)	0.006
2 yr OS rates	26.4±3.4%	29.4±3.6%
5 yr OS rates	3.8±1.8%	10.1±2.5%
median OS (months)	14	15

Results Between 04/2013 and 02/2021 525 pts were enrolledin 47 sites. 402 pts received IC with FOLFIRINOX and 93 ptswith Gem. After IC 159 pts were excluded due to progressionor toxicity, 336 were randomized, their median FU was 16 months. Hematological toxicities were significantly increased with CRT, non-hematological toxicities were comparable.

R0 resection, CRM- resection and pCR rate were significantly higher in the CRT arm. R1 resections occurred significantly more often in the CT arm. OS (HR 0.936, 95% CI 0.747-1.174, p=0.567) did not differ significantly in both arms, but the 5-year OS rates display a 2.7-fold survival benefit in the CRT arm.

OS rates for R0 resection with 49.9±5.9% (2y) and 27.6±6.0% (5y) were significantly higher (p<0.01) than for R1 resection with 23.8±9.3% (2y) and 11.9±7.6% (5y) as well as for pts without or incomplete surgery with 21.6±2.7% (2y)and 0% (5y).

Conclusion The addition of radiotherapy after IC improves the resection outcome (R status, CRM status) and pCR ratewithout improving the survival data significantly. Patients with R0 resections had a better prognosis compared to pts with either R1 resection, incomplete or no surgery.

präsentiert in der Sitzung: Pankreaskarzinom 2023 – Update: Risikofaktoren, Bildgebung, Endosonographie, (Radio)Chemotherapie und ResektabilitätDonnerstag, 14. September 2023, 14:30–16:00, Saal 4

Publication History

Article published online:
28 August 2023