93P - Next generation ALK inhibitors and metastatic NSCLC with ALK gene rearrangements, a 2 × 2 head to head comparison using RWD from TriNetX database

Background

The therapeutic landscape of NSCLC has revolutionized since the development of ALK inhibitors. Alectinib, Brigatinib and Lorlatinib are distinct with unique advantages in terms of efficacy, CNS penetration, and resistant mutation coverage. Wich ALK inhibitor should be a standard first-line treatment for metastatic NSCLC with ALK rearrangements remains to be estabilished. This RWD analysis aims to evaluate the overall survival profile, related to the outcome of death, among these 3 different drugs.

Methods

TriNetX is a global federated network of electronic medical records from 119 healthcare organizations, comprising 145,326,198 patients. Data was retrospectively collected and analyzed for the outcome of death in the time window that started 1 days after the first occurrence of the index event of metastatic malignant neoplasm of lung (based on ICD code) and NIH/NLM RxNorm (for each drug). PSM (propensity score matching) over 34 clinical characteristics balanced covariates, reduced selection bias and improved casual inference. Kaplan-Meier, Log-Rank, Hazard Ratio and test for Proportionality were produced.

Results

Analysis 1 - lorlatinib (n=285) vs alectinib (n=285), median follow-up (mFU) was 908 and 553 days. Survival probability was 61.6% and 62.7%, respectively. HR=0.91 (95% CI=0.654–1.282; p=0.11). Long-rank (X²=0.263, p=0.608). Analysis 2, brigatinib (n=139) vs alectinib (n=139), mFU was 454 and 693 days. Survival probability was 44% vs 71%, respectively. HR=1.78 (95% CI=1.123–2.842; p=0.042). Long-rank (X²=6.171, p=0.013). Analysis 3, brigatinib (n=126) vs lorlatinib (n=126), mFU of 447 and 918 days. Survival probability was 53% vs 60%, respectively. HR=1.67 (95% CI=1.046–2.692; p=0.057). Long-rank (X²=4.70, p=0.030).

Conclusions

Our RWDtrial directly compared, in a 2 × 2 basis, the main currently available ALK TKI, revealing an overall survival profile that favours alectinib and lorlatinib as first-line choice over brigatinib. Due to frailties inherent to RWD analysis, we were not able to balance cohort according to PFS2 (that may influence overall survival), to set an outcome of lung cancer specific death or to set ALK rearrangement status/variants as statification factors.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.