Objective responses to Rozlytrek were seen across 10 different solid tumour types (median duration of response [DoR] = 10.4 months), including in people with and without CNS metastases
The overall cumulative incidence of CNS metastases
was 22.8% for the neratinib plus capecitabine arm and 29.2% for the lapatinib plus capecitabine arm (p=0.043, descriptive).
These data show that checkpoint inhibitors can be similarly effective in CNS metastases
as they can be in extracranial metastases related to melanoma, Samra Turajlic, MD, PhD, and James Larkin, FRCP, PhD, of the Renal and Skin Units at the Royal Marsden National Health Service Foundation Trust in London, wrote in an accompanying editorial (N Engl J Med.
The product is a third-generation and irreversible EGFR-TKI designed to suppress both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against CNS metastases
However, it has also increased the incidence of CNS metastases
, which usually develop after long-term treatment.
Lung tumors metastasize very early, within the first 2 years, and 10% of patients with small cell lung carcinoma already have CNS metastases
at the time of diagnosis of the primary tumor (20).
Of the patients evaluated, 11 had CNS metastases
at baseline as assessed by Investigator, and 83% of the patients with measurable CNS metastases
at presentation had confirmed intracranial RECIST responses to treatment with entrectinib.
Neuroimaging revealed CNS metastases
in 19 patients, 5 girls and 14 boys, aged 5-22 years at the moment of brain metastases diagnosis (MRI in 11 cases, CT in 8) out of 550 reviewed patients' files.
Genotyping the primary tumor alone can miss substantial targeted therapy opportunities for CNS metastases
; however, routine brain biopsies are simply unfeasible.
Patients with CNS metastases
and other serious non-malignant co-existent disease were excluded.
(5-7) Stratifying patients with breast cancer and CNS metastases
into prognostically significant groups is of potential benefit for purposes of individualized therapy.