Low-Dose Erlotinib An Option For Elderly, Frail Patients with EGFR-Positive NSCLC

Author: By Laura Cowen, medwireNews Reporter 

medwireNews: Low-dose erlotinib could be a feasible treatment option for elderly or frail patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), phase II study findings indicate. 

The study authors report that 60% of the 80 enrolled patients (median age 80 years, 68% men) had an independently adjudicated objective response after 4 weeks of treatment with erlotinib 50 mg/day, equalling the predefined criteria for efficacy. 

The participants were recruited from 21 Japanese institutions on the basis of age and frailty and included those aged 81 years and older with any age-adjusted Charlson Comorbidity Index (a-CCI) and ECOG performance status (PS; n=37), those aged 75 to 80 years with an a-CCI of 6 points or higher and/or a PS of 1 or higher (n=28), and those aged 20–74 years with an a-CCI of 6 points or higher and/or a PS of 2 or higher (n=15). 

The disease control rate among the patients was 90%, and after a median 28.7 months of follow-up, median progression-free survival (PFS) duration was 9.3 months. The median overall survival (OS) time was 26.2 months. 

The objective response rates did not differ significantly among the three groups of patients but multivariate analysis adjusted for potential confounders revealed that a PS of 2 or worse was associated with significantly shorter PFS (hazard ratio [HR]=1.98) and OS (HR=1.83). 

A CCI (without age adjustment) of 2 or more was also significantly associated with shorter PFS (HR=1.98), while patients aged 80 years or older were significantly more likely to achieve a complete or partial response than younger patients (odds ratio=1.88). 

The median erlotinib treatment duration at a dose of 50 mg was 6.0 months. Five (6.3%) patients had their erlotinib dose reduced to 25 mg due to oral mucositis, paronychia, erythema multiforme, diarrhoea, and anorexia, and two patients discontinued treatment because of adverse events (AEs; cutaneous ulcer and bone infection in one patient and oral mucositis in the other). Ten patients temporarily suspended treatment due to AEs. 

The rate of grade 3 or higher AEs was 17.5%, most commonly elevated alkaline phosphatase (5.0%) and anaemia (3.8%), but the researchers attribute many of the identified laboratory abnormalities to pre-existing conditions. There were no cases of interstitial lung disease or treatment-related deaths. 

Pharmacokinetic analysis gave a median erlotinib plasma concentration of 685 ng/mL, which the authors say surpasses the previously reported effective level of 500 ng/mL. They also found that plasma erlotinib concentrations were not significantly associated with treatment response. 

Writing in JAMA Oncology, Kazuhiko Yamada, from Kurume University School of Medicine in Japan, and co-authors suggest that the conventional dosing strategy of target-based drugs based on maximum tolerated dose may be suboptimal in elderly or frail patients with EGFR-positive NSCLC because “low-dose erlotinib could achieve effective plasma concentration and clinical efficacy”. 

They add: “With the increased number of elderly and frail patients with cancer, more patients would receive benefit from this value-based treatment to enhance risk-benefit and cost-benefit ratios. In fact, our low-dose erlotinib therapy could substantially reduce the treatment cost.” 

The researchers therefore conclude: “More research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.” 

Reference 

Miyamoto S, Azuma K, Ishii H, et al. Low-dose erlotinib treatment in elderly or frail patients with EGFR mutation-positive non-small cell lung cancer. A multicenter phase 2 trial. JAMA Oncol; Advance online publication 14 May 2020. doi: 10.1001/jamaoncol.2020.1250