Del
presente trabajo se pueden hacer algunas preguntas y comentarios: Si el número de
pacientes que los autores creían necesario para tener error α y β adecuados ¿porque se suspendió la incorporación antes? provocando una alteración estadística irreparable. Un tiempo libre a la progresión de
1.8 meses no es para celebrar.
Un
aumento de la supervivencia con un HR cuyo IC está por debajo y por encima 1
no es muy creíble que sea útil.
Es
probable que se quiera imponer el bevacizumab en todas las líneas del
tratamiento sistémico del cáncer colorrectal, pero en la mayoría de los
trabajos el fundamento es muy pobre. De la calidad de vida no se habla y mucho
menos de los costos.
On behalf
of the BEBYP Study Investigators
Abstract
Background The combination of bevacizumab
with fluorouracil-based chemotherapy is a standard first-line treatment option
in metastatic colorectal cancer. We studied the efficacy of continuing or
reintroducing bevacizumab in combination with second-line chemotherapy after
progression to bevacizumab-based first-line therapy.
Patients and Methods In this phase III study
patients with metastatic colorectal cancer treated with fluoropyrimidine-based
first-line chemotherapy plus bevacizumab were randomized to receive in second-line
mFOLFOX-6 or FOLFIRI (depending on first-line regimen) with or without
bevacizumab. The primary end-point was progression-free survival. To detect an
HR for progression of 0.70 with an α and β error of
0.05 and 0.20 respectively, 262 patients were required.
Results In consideration of the results of the
ML18147 trial the study was prematurely stopped. Between April 2008 and May 2012, a total of 185
patients were randomized. Bevacizumab-free interval was longer than 3 months in
43% of patients in chemotherapy alone arm and in 50% of patients in the
bevacizumab arm. At a median follow-up of 45.3 months, median progression-free
survival was 5.0 months in the chemotherapy-group and 6.8 months in the
bevacizumab-group (adjusted HR=0.70; 95%CI 0.52-0.95; stratified log-rank p=0.010).
Subgroup analyses showed a consistent benefit in all subgroups analysed and in
particular in patients who had continued or reintroduced bevacizumab. An
improved overall survival was also observed in the bevacizumab arm (adjusted
HR=0.77; 95%CI 0.56-1.06; stratified log-rank p=0.043). Responses
(RECIST 1.0) were similar in the chemotherapy- and bevacizumab-groups (17% and
21%; p=0.573). Toxicity profile was consistent with previously reported data.
Conclusions This study demonstrates that
the continuation or the reintroduction of bevacizumab with second-line
chemotherapy beyond first progression improves the outcome and supports the use
of this strategy in the treatment of metastatic colorectal cancer.
