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. 2024 Feb;130(2):233-241.
doi: 10.1038/s41416-023-02496-4. Epub 2023 Nov 23.

Efficacy and quality of life for FOLFOX/bevacizumab +/- irinotecan in first-line metastatic colorectal cancer-final results of the AIO CHARTA trial

Hans-Joachim Schmoll  1 , Julia Mann  2 , Fabian Meinert  1 , Benjamin Garlipp  3 , Kersten Borchert  4 , Arndt Vogel  5 , Eray Goekkurt  2 , Ulrich Kaiser  6 , Heinz-Gert Hoeffkes  7 , Jörn Rüssel  1 , Stephan Kanzler  8 , Thomas Edelmann  9 , Helmut Forstbauer  10 , Thomas Göhler  11 , Carla Hannig  12 , Bert Hildebrandt  13 , Carsten Roll  4 , Carsten Bokemeyer  2 , Jörg Steighardt  14 , Franziska Cygon  1 , Stefan Ibach  15 , Alexander Stein #  2 , Joseph Tintelnot #  16
Affiliations

Efficacy and quality of life for FOLFOX/bevacizumab +/- irinotecan in first-line metastatic colorectal cancer-final results of the AIO CHARTA trial

Hans-Joachim Schmoll et al. Br J Cancer. 2024 Feb.

Abstract

Background: FOLFOXIRI plus bevacizumab has demonstrated benefits for metastatic colorectal cancer (mCRC) patients. However, challenges arise in its clinical implementation due to expected side effects and a lack of stratification criteria.

Methods: The AIO "CHARTA" trial randomised mCRC patients into clinical Group 1 (potentially resectable), 2 (unresectable/risk of rapid progression), or 3 (asymptomatic). They received FOLFOX/bevacizumab +/- irinotecan. The primary endpoint was the 9-month progression-free survival rate (PFSR@9). Secondary endpoints included efficacy in stratified groups, QoL, PFS, OS, ORR, secondary resection rate, and toxicity.

Results: The addition of irinotecan to FOLFOX/bevacizumab increased PFSR@9 from 56 to 67%, meeting the primary endpoint. The objective response rate was 61% vs. 69% (P = 0.21) and median PFS was 10.3 vs. 12 months (HR 0.83; P = 0.17). The PFS was (11.4 vs. 12.9 months; HR 0.83; P = 0.46) in potentially resectable patients, with a secondary resection rate of 37% vs. 51%. Moreover, Group 3 (asymptomatic) patients had a PFS of 11.1 vs. 16.1 months (HR 0.6; P = 0.14). The addition of irinotecan did not diminish QoL.

Conclusion: The CHARTA trial, along with other studies, confirms the efficacy and tolerability of FOLFOXIRI/bevacizumab as a first-line treatment for mCRC. Importantly, clinical stratification may lead to its implementation.

Trial registration: The trial was registered as NCT01321957.

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Conflict of interest statement

HJS received honoraria and travel grants for lectures and advisory board meetings from Roche, Merk, Servier, AstraZeneca, Novartis, Sanofi, BMS. KB received honoraria for lectures and advisory board meetings Amgen, Roche, Sanofi-Aventis, Servier, Merck Serono. BH received personal fees and/or grants from Amgen, Bayer, Janssen, Lilly, Merck, Roche, Sanofi and Teva. AV received honoraria for lectures and advisory board meetings from Roche, Bayer, Sanofi, BMS, Lilly, Novartis, EISAI, AstraZeneca, Merck, Incyte, Medac, Ipsen, Servier, PierreFabre, MSD, BTG, Janssen and research funding from Servier. CB received institutional research grants and honoraria for lectures and advisory board meetings from Merck Darmstadt, BMS, Roche, Sanofi, Bayer Healthcare, AstraZeneca, Hexal, MSD, BioNTech, ODC and AOK Healthcare. AS received institutional research grants from Merck, BMS, Roche, Sanofi, Servier, German Cancer Aid and Federal Joint Committee and honoraria for lectures and advisory board meetings by Merck, Roche, Amgen, Lilly, Sanofi-Aventis, Servier, Bayer, BMS, MSD and Sirtex. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Consort diagram showing patients’ disposition.
The number of assined, allocated, excluded, analyzed and treated patients are indicated.
Fig. 2
Fig. 2. Dose intensity and duration of treatment according to clinical groups.
a Time of treatment is shown as the median time of treatment in days per treatment arm. Dose reductions (-at least 5% of medication) during the induction phase of the study are shown as relative per treatment arm for oxaliplatin (b), 5-FU (c) or irinotecan (d). The relative applied dosage of oxaliplatin (e), 5-FU (f) or irinotecan (g) was calculated as relative to the maximal applied dosage per protocol and patient. *P < 0.05, **P < 0.001, ***P < 0.0001, determined by two-tailed chi-square test (b, c) or unpaired t test (e–g). Arm A is FOLFOX/bevacizumab and arm B FOLFOXIRI/bevacizumab.
Fig. 3
Fig. 3. PFS and OS in total study cohort or divided by clinical Groups.
a The Kaplan–Meier estimator for the respective treatment arm of the total mITT population is shown. The number of patients per arm and timepoint and median PFS interval is indicated. b As in (a), except OS is shown for respective arms. c The Kaplan–Meier estimator for respective clinical groups and treatment arms is shown. The number of patients per group and median PFS interval is indicated. d As in (a), except OS is shown for respective groups. Arm A is FOLFOX/bevacizumab and arm B FOLFOXIRI/bevacizumab.
Fig. 4
Fig. 4. Median GHS/QoL in total population or clinical Groups 1, 2 and 3 during treatment with FOLFOX/bevacizumab +/− irinotecan.
Median GHS scores were calculated as described in “Methods”. Number of patients per group and treatment arm are indicated. Median GHS scores were reported for total mITT population or respective clinical groups and treatment arms at timepoints 0, 8, 16 or 24 weeks of treatment.
See this image and copyright information in PMC

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