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Modest, Dominik P.; Stintzing, Sebastian; Fischer von Weikersthal, Ludwig; Decker, Thomas; Kiani, Alexander; Vehling-Kaiser, Ursula; Al-Batran, Salah-Eddin; Heintges, Tobias; Lerchenmüller, Christian; Kahl, Christoph; Seipelt, Gernot; Kullmann, Frank; Scheithauer, Werner; Kirchner, Thomas; Jung, Andreas; Stauch, Martina; Einem, Jobst Christian von; Möhler, Markus; Held, Swantje und Heinemann, Volker (2017): Relation of early tumor shrinkage (ETS) observed in first-line treatment to efficacy parameters of subsequent treatment in FIRE-3 (AIOKRK0306). In: International Journal of Cancer, Bd. 140, Nr. 8: S. 1918-1925

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Abstract

We explored the association of early tumor shrinkage (ETS) and non-ETS with efficacy of first-line and consecutive second-line treatment in patients with KRAS wild-type metastatic colorectal cancer treated in FIRE-3. Assessment of tumor shrinkage was based on the sum of longest diameters of target lesions, evaluated after 6 weeks of treatment. Shrinkage was classified as ETS (shrinkage by >= 20%), mETS (shrinkage by 0 to < 20%), mPD (minor progression > 0 to < 20%) and PD (progression >= 20%). Overall survival (OS) was 33.2 (95% CI 28.0-38.4) months in ETS patients, while non-ETS was associated with less favorable outcome (mETS 24.0 (95% CI 21.2-26.9) months, mPD 19.0 (95% CI 13.0-25.0) months, PD 12.8 (95% CI 11.1-14.5) months). Differences in PFS of first-line therapy were less pronounced. ETS subgroups defined in first-line therapy also correlated with efficacy of second-line therapy. Progression-free survival in second-line (PFS2nd) was 6.5 months (5.8-7.2) for ETS, and was 5.6 (95% CI 4.7-6.5) months for mETS, 4.9 (95% CI 3.7-6.1) months for mPD and 3.3 (95% CI 2.3-4.3) months for PD. PFS of first-line and PFS2nd showed a linear correlation (Bravais-Pearson coefficient: 0.16, p = 0.006). While ETS is associated with the most favorable outcome,non- ETS represents a heterogeneous subgroup with distinct characteristics of less favorable initial tumor response to treatment. This is the first analysis to demonstrate that early tumor response observed during first-line FOLFIRI-based therapy may also relate to efficacy of second-line treatment. Early response parameters may serve as stratification factors in trials recruiting pretreated patients.

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