Department of Hematology and Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, LMU Munich, Munich, Germany
Sebastian Stintzing , Dominik Paul Modest , Ludwig Fischer von Weikersthal , Thomas Decker , Alexander Kiani , Ursula Vehling-Kaiser , Salah-Eddin Al-Batran , Tobias Heintges , Christian A. Lerchenmuller , Christoph Kahl , Gernot Seipelt , Frank Kullmann , Martina Stauch , Werner Scheithauer , Swantje Held , Clemens Albrecht Giessen , Markus Hermann Moehler , Andreas Jung , Thomas Kirchner , Volker Heinemann
Background: The FIRE-3 study (AIO KRK-0306) was designed to compare the efficacy of FOLFIRI + cetuximab (cet) to FOLFIRI + bevacizumab (bev) as first-line treatment in KRAS WT mCRC patients. FOLFIRI plus cet resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI + bev. Overall survival (OS) was significantly longer in the FOLFIRI + cet arm. Methods: In an exploratory subgroup analysis, patients pretreated with adjuvant chemotherapy were analyzed by Fisher's exact and log rank-test according to tumor response (ORR) and survival data. Patients of the ITT (n=592) and the final RAS wild-type population (n=400) were investigated. Results: See table. Conclusions: Results in patients treated with any adjuvant chemotherapy mirrored those in the whole study population. In adjuvant pretreated RASwt patients a significantly higher ORR was reached in the cet arm when compared to the bev arm (p=0.01). The role of adjuvant treatment on efficacy of first-line therapy remains to be further evaluated. Clinical trial information: NCT00433927
Patients with any adjuvant chemotherapy (n=124) | ||||
---|---|---|---|---|
KRAS exon 2 wt | FOLFIRI + Cet N=68 | FOLFIRI + Bev N= 56 | P* | HR |
ORR (%) | 60.3 | 48.2 | 0.21 | |
PFS (95% CI) | 9.4 (7.4 – 12.3) | 9.7 (8.8 – 10.8) | 0.36 | 1.19 |
OS (95% CI) | 33.1 (23.7 – 49.8) | 25.6 (19.4 – 42.9) | 0.26 | 0.77 |
Patients pretreated with oxaliplatin (n=58) | ||||
KRAS exon 2 wt | FOLFIRI + Cet N= 34 | FOLFIRI + Bev N= 24 | P* | HR |
ORR (%) | 58.8 | 50.0 | 0.36 | |
PFS (months) (95% CI) | 10.2 (6.8 – 12.8) | 10.3 (8.8 – 12.0) | 0.30 | 1.34 |
OS (months) (95% CI) | 33.1 (23.7 – 38.5) | 44.3 (23.7 – 49.9) | 0.58 | 1.22 |
Patients with any adjuvant chemotherapy (n=75) | ||||
---|---|---|---|---|
RASwt | FOLFIRI + Cet N=37 | FOLFIRI + Bev N= 38 | P* | HR |
ORR (%) | 73.0 | 42.1 | 0.01 | |
PFS (months) (95% CI) | 10.2 (6.8 – 12.3) | 9.6 (8.6 – 10.7) | 0.84 | 1.05 |
OS (months) (95% CI) | 38.3 (25.2 – 52.0) | 25.6 (19.4 – 35.0) | 0.22 | 0.70 |
Patients pretreated with oxaliplatin (n=36) | ||||
RASwt | FOLFIRI + Cet N= 19 | FOLFIRI + Bev N= 17 | P* | HR |
ORR (%) | 73.7 | 47.1 | 0.17 | |
PFS (months) (95% CI) | 10.2 (7.2 – 13.3) | 9.9 (8.6 – 11.9) | 0.59 | 1.2 |
OS (months) (95% CI) | 27.9 (18.3 – 52.0) | 44.3 (23.7 – 58.7) | 0.42 | 1.44 |
*p= log rank test p for OS and PFS, 2-sided Fisher’s exact test for ORR.
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Abstract Disclosures
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First Author: Sebastian Stintzing