Research Student Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, Canada
Background: Patients (Pts) diagnosed at earlier stages are typically followed more closely clinically and radiologically at the time of metastatic recurrence, when compared to pts who develop initial metastatic disease (de novo metastatic pts; DNMPs). Thus, recurrent metastatic pts (RMPs) may have better outcomes due to better performance status at diagnosis and lower disease burden. We tested this hypothesis in DNMPs and RMPs with non-small cell lung cancer (NSCLC) who have either targetable KRAS^G12C mutations (older, heavy smokers) or ALK fusions (younger, never smokers).
Objectives: To compare patterns in the presentation, treatments, and outcomes of NSCLC DNMPs vs. RMPs, with KRAS^G12C-mutated or ALK-fusion NSCLC DNMPs vs. RMPs.
Methods: Through retrospective chart review, clinico-demographic variables and treatment information were captured in patients diagnosed with stage IV DNMPs and RMPs with KRAS^G12C-mutated or ALK-fusion NSCLC between Jan 1, 2013 to Dec 31, 2021 at Princess Margaret Cancer Centre. Statistical analyses were conducted using R package (version 4.1.3).
Results: Of 53 DNMPs and 31 RMPs with KRAS^G12C-mutations, most were current/34% or ex-smokers/57%; 76% of ALK-fusion patients (117 DNMPs, 31 RMPs) were never smokers. Median age was 68 and 60 years for KRAS^G12C and ALK-rearranged patients respectively. No baseline clinico-demographic differences were found between DNMPs and RMPs except that DNMPs had worse baseline ECOG performance scores compared to RMPs (p=0.007, KRAS; p=0.035, ALK). KRAS^G12C DNMPs had more extra-thoracic metastatic sites at Stage IV diagnosis (p=0.017) and were less likely to receive any palliative systemic therapy (59% vs 83%; p=0.028) including 1st, 2nd, and 3rd-line systemic therapy (p < 0.02, each comparison). In contrast, the number of extra-thoracic metastatic sites was similar for ALK-fusion pts with DNMP vs. RMPs, and a similar proportion of pts received palliative systemic therapy. The use of tyrosine kinase inhibitors (TKIs) was more common in 2nd and subsequent line for KRAS^G12C pts, but was most common in the first line for pts with ALK-fusions. Whereas KRAS^G12C DNMPs had shorter overall survival than recurrent patients (10.3 vs 31.6 months; p=0.05), ALK fusion DNMPs had similar overall survival to RMPs (56.3 vs 47.7 months; p=0.92).
Conclusions: The differential influence of de novo vs. recurrent metastatic disease in KRAS^G12C-mutated and ALK-fusion NSCLC pts is likely due to the intrinsic pattern of metastatic disease at Stage IV presentation, line of first use of TKI therapy, and drop-out rates in between lines of therapy. Whether a patient is a DNMP or RMP may be an important factor to consider in real-world cancer data analyses in some, but not all, molecular subsets of NSCLC pts.
