Metronomic chemotherapy has emerged as an effective treatment option with low toxicity for elderly and unfit patients. In an interview with MIMS Oncology, Dr Ashley Cheng, Specialist in Clinical Oncology in private practice in Hong Kong, discussed use of metronomic oral vinorelbine (m-OV) in frail patients with advanced non-small-cell lung cancer (NSCLC) and highlighted its advantages, including convenience and favourable tolerability.
Treatment considerations for frail patients
Up to 40 percent of advanced NSCLC patients are >70 years of age. While older patients are often frailer due to age-related health issues, other factors, including performance status (PS), comorbidities, and organ function, should also be considered when deciding on most appropriate therapy. [BMC Cancer 2015:15:359; ESMO Open 2021;6:100051]
“When treating advanced NSCLC in elderly or frail patients, we start with targeted therapy for tumours with actionable mutations and use immunotherapy monotherapy for those with PD-L1 expression ≥50 percent,” said Cheng. “If neither option is suitable, chemotherapy combinations with milder side effects and lower starting doses are used as first-line treatment.”
Efficacy and safety of metronomic oral vinorelbine
m-OV is a well-tolerated option for frail patients, involving consistent administration of low-dose chemotherapy that helps prolong disease control while minimizing toxicity. It suppresses tumour growth through multiple mechanisms, including inhibition of angiogenesis. [Biomed Res Int 2018:2018:6278403; Curr Oncol 2017;24:e199-e204; ESMO Open 2021;6:100051]
“m-OV is suitable for patients who are unfit for standard chemotherapy or have failed multiple lines of treatment and cannot use other aggressive regimens,” said Cheng.
The MOVE trial, which investigated m-OV regimen (50 mg Q3W) as first-line treatment in 43 chemotherapy-naïve elderly (median age, 80 years) patients with stage IIIB–IV NSCLC, reported an overall response rate of 18.6 percent (complete response, 2.3 percent; partial response, 16.3 percent) and stable disease lasting >12 weeks in 39.5 percent, amounting to an overall clinical benefit rate of 58.1 percent. Treatment was well tolerated with rare serious toxicity, and treatment compliance was high. [BMC Cancer 2015:15:359]
The TEMPO-LUNG trial (n=167; median age, 77 years) evaluated the efficacy and safety of m-OV as first-line treatment for patients with advanced NSCLC who were unfit for platinum-based combination chemotherapy. Patients who received the metronomic oral regimen (50 mg Q3W) achieved longer progression-free survival (PFS) without grade 4 toxicity (4.0 vs 2.2 months; p=0.0068) compared with those on the standard weekly schedule of intravenous (IV) vinorelbine (60–80 mg/m²). (Figure) Patients treated with m-OV also had a higher disease control rate without grade 4 toxicity than the standard arm (45.8 vs 26.8 percent). [ESMO Open 2021;6:100051]
“While the MOVE and TEMPO-LUNG trials showed stable or comparable quality of life (QoL) with m-OV, in my experience, patients often report improved QoL during treatment,” shared Cheng. [BMC Cancer 2015:15:359; ESMO Open 2021;6:100051]
“It is possible to further enhance the efficacy of m-OV by combining it with other treatments, such as immunotherapy,” Cheng commented. According to data in Chinese patients presented at American Society of Clinical Oncology Annual Meeting 2025, m-OV combined with PD-1 inhibitors as first-line treatment for elderly patients with driver-gene–negative metastatic NSCLC achieved a median PFS of 10.9 months. [Li L, et al, ASCO 2025, abstract 8564]
Most adverse events (AEs) associated with m-OV, including nausea, diarrhoea, and vomiting, are similar to the standard IV regimen, but are less intense and less frequent. In the TEMPO-LUNG trial, substantially fewer grade 3–4 treatment-related AEs were reported in the m-OV than the standard arm (25.3 vs 54.4 percent). [ESMO Open 2021;6:100051]
With good tolerability and convenient oral administration, m-OV treatment compliance is high. “The convenience of at-home treatment coupled with noticeable symptom improvements further encourage adherence,” Cheng added. [ESMO Open 2021;6:100051]
Dosing strategies for better tolerability
“To optimize disease control while minimizing side effects, elderly or unfit patients can start the m-OV regimen at 30 mg/m² to assess tolerability and response, and escalate the dose to 40 or 50 mg/m² if feasible,” Cheng shared.