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Relation of early tumor shrinkage (ETS) observed in first‐line treatment to efficacy parameters of subsequent treatment in FIRE‐3 (AIOKRK0306)
Author(s) -
Modest Dominik P.,
Stintzing Sebastian,
Fischer von Weikersthal Ludwig,
Decker Thomas,
Kiani Alexander,
VehlingKaiser Ursula,
AlBatran SalahEddin,
Heintges Tobias,
Lerchenmüller Christian,
Kahl Christoph,
Seipelt Gernot,
Kullmann Frank,
Scheithauer Werner,
Kirchner Thomas,
Jung Andreas,
Stauch Martina,
von Einem Jobst Christian,
Moehler Markus,
Held Swantje,
Heinemann Volker
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30592
Subject(s) - shrinkage , line (geometry) , first line treatment , medicine , materials science , mathematics , composite material , chemotherapy , geometry
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.