Clinical Study

Is there a role for rechallenge and reintroduction of anti-EGFR plus chemotherapy in later lines of therapy for metastatic colorectal carcinoma? A retrospective analysis

10 Jul 2020
Amanda Karani, Tiago Cordeiro Felismino, Lara Diniz, Mariana Petaccia Macedo, Virgilio Souza e Silva, Celso Abdon Mello

Background: Mechanisms of resistance have been described during disease progression (PD) for patients under treatment with anti-EGFR plus chemotherapy (CT). The aim of our study was to evaluate efficacy of anti-EGFR rechallenge (ReCH) and reintroduction (ReIn) in metastatic colorectal cancer (mCRC).

Materials and methods: This is a retrospective analysis of patients with mCRC that previously received anti-EGFR CT and interrupted therapy due to PD in the ReCH group and other reasons in the ReIn group. We aimed to describe progression-free survival (PFS), overall survival (OS) and response rate (RR) after re-exposure and to evaluate prognostic factors associated with PFS.

Results: Sixty-eight patients met the inclusion criteria. The median follow-up after re-exposure was 39.3 months. ReCH was adopted in 25% and ReIn in 75%. The median anti-EGFR free interval was at 10.5 months. At re-exposure, the main CT regimen was FOLFIRI in 58.8%. Cetuximab and Panitumumab were used in 59 and 9 patients, respectively. mPFS for ReCH and ReIn was 3.3 × 8.4 months, respectively (p 0.001). The objective response rate for ReCH and ReIn was 18% and 52%, respectively. In univariate analysis, adverse prognostic factors related to PFS were: stable disease or PD at first anti-EGFR exposure (HR: 2.12, CI:1.20–3.74; p = 0.009); ReCH (HR: 3.44, CI:1.88–6.29, p < 0.0001); rechallenge at fourth or later lines (HR: 2.51, CI:1.49–4.23, p = 0.001); panitumumab use (HR: 2.26 CI:1.18–5.54, p = 0.017). In the multivariate model, only ReCH remained statistically significant (HR = 2.63, CI: 1.14–6.03, p = 0.022).

Conclusion: In our analysis, ReCH resulted in short PFS and low RR. However, reintroduction of anti-EGFR plus CT before complete resistance arose resulted in prolonged PFS. These data could be clinically useful to guide a treatment break due to side effects or patient decisions. Our data should be confirmed by larger and prospective trials.

Related Articles

Marcello Moro Queiroz, Zenaide Silva de Souza, Aline Bobato Lara Gongora, Felipe de Galiza Barbosa, Carlos Alberto Buchpiguel, Marilia Germanos de Castro, Mariana Petaccia de Macedo, Rafael Ferreira Coelho, Ethan Samuel Sokol, Anamaria Aranha Camargo, Diogo Assed Bastos
Prasanth S Ariyannur, Reenu Anne Joy, Veena Menon, Roopa Rachel Paulose, Keechilat Pavithran, Damodaran M Vasudevan
Renata Colombo Bonadio, Ana Paula Messias, Otavio Augusto Moreira, Letícia Vecchi Leis, Bruna Zanin Orsi, Laura Testa, Maria del Pilar Estevez-Diz
Safiya Karim, Zahra Sunderji, Matthew Jalink, Sahar Mohamed, Indranil Mallick, Susan Citonje Msadabwe-Chikuni, Nancy J Delgarno, Nazik Hammad, Scott Berry