Evgenia Kuzmina, Mikhail Fedyanin, Igor Reshetov, Sergey Parts, Ilya Pokataev, Maxim Polyanskiy, Tatiana Antonova, Dmirii Pikulin, Evgenia Arseneva, Marina Anikina, Pavel Golubev, Anna Syskova, Vsevolod Galkin; State Medical Institution “City Clinical Oncological Hospital No. 1”, Moscow, Russian Federation; N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation; Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation, Moskow, Russian Federation; State Medical Institution “City Clinical Oncological Hospital No. 1”, Moskow, Russian Federation; City Clinical Oncological Hospital No. 1, Moscow, Russian Federation; City Clinical Oncology Hospital, Moscow, Russian Federation
Background: Regorafenib is considered the standard third-line therapy of mCRC. However, the modest efficacy and significant toxicity of regorafenib urges the search for new therapeutic approaches. In various countries, the re-challenge of the previously effective treatment regimens is being considered. We compared the effectiveness of various variants of systemic therapy in the third and subsequent lines of the treatment.
Methods: We analyzed the prospective database of pts with mCRC from two clinics of the Russian Federation. The statistical hypothesis implied the equivalence of the 6-month overall survival on the repeated chemotherapy (CT) and targeted therapy with the third line regorafenib therapy, provided the equivalence boundaries from 0.8 to 1.25. With a = 0.05, the study power is 80% with 178 patients, 89 people in each group. We conducted statistical analysis with the SPSS statistical software package (v. 20, IBM).
Results: In the database, we identified 215 patients with morphologically confirmed metastatic colon cancer who received two or more lines of antitumor drug therapy from 2010 to 2021. Of them, we selected 132 patients with a history of regorafenib therapy, and 83 patients with the re-challenge of CT as the third line of the therapy. Overall survival (OS) in the re-challenge and regorafenib groups did not differ (hazard ratio [HR] 1.01 with 95%CI 0.7-1.45; p = 0.9) and the 6- month OS was 74 and 70%, respectively. Progression-free survival was significantly higher in the rechallenge group (HR 1.94 with 95%CI 1.3-2.7; p , 0.001); In the multifactorial analysis, the rechallenge of previous treatment regimens kept its independent positive effect on progression-free survival (HR 1.9 with 95%CI 1.3-2.8; p = 0.0001) also as index T , 3 (HR 0.7, 95CI 0.55-0,94); ECOG $1 a (HR 1.5 with 95%CI 1.16-2.05; p , 0.01) affected PFS negatively. The reduction of the regorafenib dose did not affect PFS (HR 0.9 with 95% CI from 0.9 to 1.0; p = 0.1), its starting dose (HR 0.9 with 95 CI from 0.9 to 1.0; p = 0.2), and a break in the regorafenib treatment (HR 0.9 with 95% CI from 0.5 to 1.8; p = 0.9).
Conclusions: Regorafenib and the re-challenge of previously effective CT in the third-line of mCRP therapy show the similar 6-mon. OS. However, progression-free survival is significantly higher in the re-challenge group in third line therapy. Research Sponsor: None.