Zie ook literatuurlijst niet-toxische middelen en behandelingen specifiek bij darmkanker van arts-bioloog drs. Engelbert Valstar

16 november 2020: Bron: British Journal of Cancer

Uit een fase III studie, (FIRE 3) blijkt dat darmkankerpatiënten met een KRAS wild type beter cetuximab kunnen krijgen naast FOLFIRI chemo (5-fluorouracil, folinic acid en irinotecan) dan Avastin - betacizumab. De overall overleving blijkt 5 maanden meer te bedragen voor cetuximab in vergelijking met Avastin- bevacizumab.

De onderzoekers evalueerden een subgroep van 352 patiënten met uitgezaaide dammkanker van het wild type KRAS die werden behandeld in de gerandomiseerde fase III studie FIRE-3 met patiënten die gerandomiseerd ingedeeld waren naar FOLFIRI plus cetuximab of Avastin - Bevacizumab.
De mediane totale overleving was statistisch beter met cetuximab (33 versus 26 maanden) in progressievrije overleving, vergelijkbaar met de bevindingen die werden gezien in de totale studiegroep. Bij het beoordelen van de locatie van de primaire tumor, was het voordeel alleen duidelijk bij patiënten met linkszijdige primaire tumoren.
Het objectieve responspercentage was hoger met cetuximab dan met bevacizumab (77% versus 65%) bij alle patiënten en was geassocieerd met een langere mediane overleving na progressie van de ziekte.

Hier het abstract van het studieverslag dat volledig ook gratis is in te zien

Article
Open Access
Published: 06 November 2020

Clinical Study

FOLFIRI plus cetuximab or bevacizumab for advanced colorectal cancer: final survival and per-protocol analysis of FIRE-3, a randomised clinical trial

Volker Heinemann,
Ludwig Fischer von Weikersthal,
Thomas Decker,
Alexander Kiani,
Florian Kaiser,
Salah-Edin Al-Batran,
Tobias Heintges,
Christoph Lerchenmüller,
Christoph Kahl,
Gernot Seipelt,
Frank Kullmann,
Markus Moehler,
Werner Scheithauer,
Swantje Held,
Lisa Miller-Phillips,
Dominik Paul Modest,
Andreas Jung,
Thomas Kirchner &
Sebastian Stintzing

British Journal of Cancer (2020)Cite this article

Abstract

Background

Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes.

Methods

The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ≥3 cycles of therapy and had ≥1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated.

Results

Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P = 0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P = 0.014) and median OS (33 vs 26 months, HR 0.75, P = 0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours.

Conclusions

FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases.

ClinicalTrials.gov identifier

NCT00433927.

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