Metronomic oral vinorelbine in previously untreated advanced non-small-cell lung cancer patients unfit for platinum-based chemotherapy: results of the randomized phase II Tempo Lung trial

Abstract

Background To assess the efficacy and safety of a metronomic schedule of oral vinorelbine (mVNR) in advanced non-small-cell lung cancer (NSCLC) in patients unfit for platinum-based combination chemotherapy. Patients and methods This was a multicenter, prospective, randomized, open-label phase II study in treatment-naive patients with TNM stage IIIB/IV NSCLC. Patients received mVNR at a fixed dose of 50 mg × 3 or standard schedule 60-80 mg/m 2 weekly until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) without grade 4 toxicity (G4PFS; NCI-CTC v4). Main secondary objectives were safety, disease control rate (DCR) without grade 4 toxicity (G4DCR), DCR, PFS, overall survival (OS) and quality of life (QoL). Results A total of 167 patients were included, 83 and 84 patients in the mVNR and standard arms, respectively. The median G4PFS was 4.0 months [95% confidence interval (CI): 2.6-4.3] and 2.2 months (95% CI: 1.5-2.9), hazard ration (HR) = 0.63 (95% CI: 0.45-0.88), P = 0.0068 in favor of metronomic arm; G4DCR was 45.8% and 26.8% in the mVNR and standard arms, respectively. Grade 3-4 treatment-related adverse events were less frequent in the mVNR arm (25.3% versus 54.4%) mainly owing to a reduction in all grades (15.7% versus 51.9%) and grade 3-4 neutropenia (10.8% versus 42%). PFS was 4.3 (95% CI: 3.3-5.1) and 3.9 months (95% CI: 2.8-5.2) in mVNR and standard arms, respectively. No difference in median OS was observed. QoL was comparable between arms. Conclusions Metronomic oral vinorelbine significantly prolonged median G4PFS in advanced NSCLC patients unfit for platinum combinations as first-line treatment. It was associated with a clear reduction in toxicity and may be considered as an important option in this challenging population.

Metronomic Chemotherapy

“…Regarding NSCLC, in our opinion that data are well consolidated in unfit advanced patients [ 78 ], for whom mCHT sometimes can represent the only option of treatment, considering that more aggressive regimens and combinations with immune check inhibitors are precluded.…”

“…A randomized Phase II Tempo Lung trial, showed that in advanced NSCLC patients unfit for platinum-based first line chemotherapy, metronomic oral VNR at a fixed dose of 50 mg thrice a week significantly prolonged median PFS without grade 4 toxicity compared to standard schedule 60–80 mg/m 2 [ 78 ].…”

A look towards the clonal origin of metastatic pulmonary carcinosarcoma: Report of a patient with an unexpected long-term survival

“…Shortly after the small bowel resection, thoracic disease progression was detected by a whole-body CT-scan; thus, the patient stopped immunotherapy (September 2020) and started third-line treatment with oral metronomic vinorelbine (30 mg x3/week continuously) together with a radiotherapy boost (12 Gy total dose). 10…”

“…7 Shortly after the small bowel resection, thoracic disease progression was detected by a whole-body CT-scan; thus, the patient stopped immunotherapy (September 2020) and started third-line treatment with oral metronomic vinorelbine (30 mg x3/week continuously) together with a radiotherapy boost (12 Gy total dose). 10 To date, the patient is still on treatment with metronomic vinorelbine. The scheduled CT-scans have showed stable disease on left chest wall and no abdominal disease recurrence.…”

Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment

“…Thus, whereas the former promoted a significant decrease, the latter showed an increase in comparison with the control group [124]. There is some clinical evidence for the efficacy and safety of metronomic vinorelbine in advanced breast cancer and NSCLC [125,126]. Metronomic topotecan with pazopanib showed antitumor activity in murine models of aggressive pediatric solid tumors and a significant reduction in viable blood CEPs and CECs and tumor microvessel density [127].…”