Impact of docetaxel plus ramucirumab on metastatic site in previously treated patients with non-small cell lung cancer: a multicenter retrospective study

Abstract

Background: Docetaxel (DOC) plus ramucirumab (RAM) has been recommended as an optimal therapy for previously treated patients with non-small cell lung cancer (NSCLC). In a clinical setting, there are few reports about DOC plus RAM, therefore its effect on factors such as Eastern Cooperative Oncology Group (ECOG) performance status (PS) and metastatic sites is still unknown.

Methods: We recruited NSCLC patients who received DOC plus RAM in four medical facilities in Japan from June 2016 to March 2020. We retrospectively investigated the overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) of DOC plus RAM and conducted univariate and multivariate analyses using PFS as a dependent factor. Patients were followed up until June 30, 2020.

Results: A total of 237 patients were consecutively enrolled. For all patients, the ORR, DCR, and median PFS were 25.2%, 63.9%, and 4.5 months, respectively. The ORR and DCR for malignant pleural effusion (MPE), lung metastasis, and liver metastasis were 7.7% and 53.8%, 30.3% and 77.5%, and 48.6% and 71.4%, respectively. In the multivariate analysis, MPE, lung metastasis, and liver metastasis were not prognostic factors for poor PFS. However, ECOG-PS 2 or more [hazard ratio (HR): 1.66, 95% confidence interval (CI): 1.14-2.40, P=0.008] and brain metastasis (HR: 1.71, 95% CI: 1.23-2.37, P=0.001) were significant and independent factors associated with shorter PFS.

Conclusions: DOC plus RAM could be an optimal therapy for previous treated NSCLC patients with lung and liver metastasis, and furthermore, should be used carefully for patients with poor ECOG-PS or brain metastasis.

Keywords: Docetaxel and ramucirumab; non-small cell lung cancer (NSCLC); metastatic site; poor performance status.

Figure 1

Kaplan-Meier survival curves of PFS and OS in all patients treated with DOC plus RAM. (A) The median PFS was 4.5 (95% CI, 3.36–5.62) months and (B) the median OS was 13.4 (95% CI, 11.7–15.1) months. PFS, progression-free survival; OS, overall survival; DOC, docetaxel; RAM, ramucirumab; CI, confidence interval.

Figure 2

Kaplan-Meier survival curves of PFS. There were no significant differences in the median PFS of patient treated with DOC plus RAM in terms of (A) age, (B) sex, and (C) smoking status; (D) Poor PS group had shorter PFS compared to good PS group significantly [2.79 (95% CI: 2.18–3.39) vs. 5.46 (95% CI: 4.42–6.51) months; P<0.001]. PFS, progression-free survival; DOC, docetaxel; RAM, ramucirumab; PS, performance status; CI, confidence interval.

Figure 3

The ORR and DCR on each metastatic site. The ORR for MPE was 7.7%, relatively low. The ORR and DCR for lung and liver metastasis were higher than those in all patients, showing 30.3% and 77.5%, and 48.6% and 71.4%, respectively. The ORR and DCR for brain metastasis were almost the same as those of all patients. ORR, overall response rate; DCR, disease control rate; MPE, malignant pleural effusion.

Figure 4

Kaplan-Meier survival curves of PFS. There were no significant differences in the median PFS of patient treated with DOC plus RAM in terms of (A) MPE, (B) lung metastasis, and (C) liver metastasis; (D) patients with brain metastasis had shorter PFS compared to patients without brain metastasis significantly [3.14 (95% CI: 2.38–3.90) vs. 5.14 (95% CI: 4.25–6.03) months; P=0.002]. PFS, progression-free survival; DOC, docetaxel; RAM, ramucirumab; MPE, malignant pleural effusion; CI, confidence interval.