Apatinib as an optional treatment in metastatic colorectal cancer

Abstract

Antiangiogenic therapy has shown clinical benefit in metastatic colorectal cancer (mCRC). We aimed to evaluate the efficacy and safety of apatinib in patients who failed standard treatment and to explore potential factors related to its efficacy.A total of 47 patients were enrolled in this retrospective study. Patients who received apatinib therapy after failure of standard therapy from December 2014 and February 2018 were included. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events were recorded and evaluated.The median PFS was 3.717 months (95% confidence interval [CI], 3.198–4.235), and the median OS was 7.335 months (95% CI, 6.738–7.932). The disease control rate was 72.34%, and the ORR was 8.51%. The most common grade 3 to 4 adverse reactions were hypertension, proteinuria, hand-foot syndrome, and diarrhea. Multivariate analysis indicated previous antiangiogenic therapy and baseline elevated neutrophil-to-lymphocyte ratio (NLR) as independent prognostic factors.Apatinib might be a reasonable treatment option with a controlled safety profile for patients with mCRC who have failed standard therapy. Patients who previously received antiangiogenic therapy and who have baseline elevated NLR are more likely to benefit from apatinib.

Apatinib Monotherapy for Chemotherapy-Refractory Metastatic Colorectal Cancer: A Multi-centre, Single-Arm, Prospective Study

“…Our results are consistent with those of recently published studies of apatinib in a similar population of patients with mCRC conducted by Guo et al, (PFS 3.8 months, OS not reached) 10 ; Liang et al, (PFS 4.8 months, OS 10.1 months) 15 ; and Li et al, (PFS 3.7 months, OS 7.3 months) 13 . This finding further supports the use of apatinib as an alternative option based on the strategy of continued administration of newer anti-angiogenic agents as the new standard of care.…”

“…The moderate initial dose in our study resulted in a more manageable toxicity profile and a lower proportion of dose modification than those in the previous studies of apatinib 850 mg in advanced gastric cancer 33,34 . Furthermore, it seems comparable to the modification reported in the studies of apatinib 500 mg in mCRC 10,[13][14][15][16] .…”

“…A higher proportion of patients exposed to subsequent systemic anticancer therapy in the naïve-to-anti-angiogenic agent-treated group (76% vs. 24%) might have contributed to the numerical OS advantage in our study. A conflicting result was reported for prior anti-angiogenic therapy as an independent factor associated with the PFS and OS of apatinib in mCRC in a real-world observation study 13 . However, the difference in study design, where >40% of patients received apatinib co-therapy in that study, makes the results incomparable.…”

“…NLR, as a laboratory marker of systemic inflammatory response, has been studied as a potential prognostic and predictive factor for several tumours including CRC. Two previous studies have demonstrated the predictive and prognostic role of NLR in bevacizumab-containing chemotherapy and apatinib in mCRC, respectively, www.nature.com/scientificreports www.nature.com/scientificreports/ with a negative impact on PFS and OS 13,40 . Likewise, our study showed NLR negatively predicted the outcome of apatinib and was an independent prognostic factor in mCRC.…”

“…It is currently approved by China Food and Drug Administration (CFDA) for treatment in the third-line settings in the patients with metastatic gastric or gastroesophageal junction adenocarcinoma. Preclinical and clinical trials have shown its vigorous antitumour activity and good tolerability in multiple malignancies including non-small cell lung cancer, triple-negative breast cancer, ovarian cancer, and colorectal cancer 7,[9][10][11][12][13][14][15][16][17][18][19][20] , Presently, the evidence that apatinib may improve survival in chemotherapy-refractory mCRC is based on limited retrospective studies 10,13,15,16 . The impact of previous anti-angiogenic therapies on the efficacy of apatinib remains unknown.…”