Low-dose erlotinib ‘a valid treatment option’ for older, frail NSCLC patients
medwireNews: A phase 2 trial suggests that low-dose erlotinib has clinical activity and a favorable safety profile among older and frail non-small-cell lung cancer (NSCLC) patients with EGFR activating mutations.
“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,” say Kazuhiko Yamada (Kurume University School of Medicine, Fukuoka, Japan) and team in JAMA Oncology.
They analyzed data from 80 patients who were enrolled across 21 Japanese institutions and received the tyrosine kinase inhibitor (TKI) erlotinib at a daily dose of 50 mg for an initial 4-week period. At the end of this period, patients with complete or partial responses, as well as those with stable disease at the physician’s discretion, continued treatment until disease progression or the onset of unacceptable adverse events (AEs). The participants received low-dose erlotinib for a median of 6 months.
The patients were stratified into three cohorts, based on distinct inclusion criteria, according to which patients were:
- above 81 years of age and had any age-adjusted Charlson Comorbidity Index (CCI) or ECOG performance status;
- aged between 75 and 80 years with an age-adjusted CCI of at least 6 points and/or a minimum performance status of 1; or
- aged between 20 and 74 years with a minimum age-adjusted CCI of 6 points and/or a performance status of at least 2.
Across all three cohorts, the independently assessed overall response rate (ORR) at 4 weeks was 60%, which met the prespecified criteria for clinical efficacy of low-dose erlotinib, and the disease control rate was 90%.
The ORRs did not significantly differ among the cohorts, at a respective 57%, 71%, and 47% for cohorts 1, 2, and 3.
After a median follow-up of 28.7 months, the median progression-free survival (PFS) was 9.3 months and median overall survival (OS) was 26.2 months in the full study cohort.
Multivariate analysis revealed that patients with a performance status of at least 2 were significantly more likely to have a shorter PFS (hazard ratio [HR]=1.98) and OS (HR=1.83), while those with an unadjusted CCI of at least 2 also had significantly worse PFS (HR=1.98).
Moreover, patients aged 80 years or older were a significant 88% more likely to achieve a complete or partial response than younger patients.
The researchers say the AEs associated with low-dose erlotinib were “mild,” and “generally manageable.” In total, 14 patients experienced a grade 3 or higher treatment-related AE, most commonly laboratory abnormalities such as anemia and elevation of alkaline phosphatase, which the researchers assert “resulted from baseline abnormalities.”
Ten patients temporarily suspended treatment due to AEs, five patients reduced their dose to 25 mg – due to oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia – and two patients discontinued treatment permanently – due to cutaneous ulcer and bone infection, and oral mucositis, respectively.
Notably, no patient had interstitial lung disease and there were no treatment-related deaths.
Plasma erlotinib concentrations were measured in 48 patients, and the median trough level was 685 ng/mL, which the researchers say “surpassed the reported effective level” of 500 ng/mL.
Yamada and team therefore reason: “Because low-dose erlotinib could achieve effective plasma concentration and clinical efficacy, the conventional dosing strategy of target-based drugs based on [maximum tolerated dose] may not be optimal.”
But the investigators acknowledge the “limited influence on the standard of care” of these findings in light of the recently published data from the FLAURA trial demonstrating the superiority of osimertinib to first-generation TKIs such as erlotinib.
“However, because the FLAURA trial enrolled only good-risk patients, the results cannot be automatically applied to real-world frail patient groups,” they say.
And the team concludes that “[m]ore research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.”
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