1095P - Concomitant genetic alterations predicted response to alectinib in patients with ALK-rearranged non-small cell lung cancer: A real word study in China

Background

Alectinib has been widely used for advanced non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) rearrangement. However, in real world, how concomitant genomic alterations impact on the efficacy of alectinib in these patients still warrant a better disclosure.

Methods

We analyzed 95 advanced NSCLC patients with ALK fusions treated with alectinib in China. ALK rearrangement was detected by IHC, PCR, or NGS. The baseline characteristics, genomic findings, and response outcomes of the patients were collected.

Results

Median age of those patients was 57.0 years [32-85]. 54 (56.84%) were female, 9 (9.47%) were smokers, 92 (96.84%) had lung adenocarcinoma, 86 (90.53%) were at stage IV, 69 (72.63%) were treated at first-line, and 50 (52.63%) were detected with NGS. As of April 2022, all patients had accomplished response evaluation. Objective response rate (ORR) and disease control rate (DCR) were 57.89% (55/95) and 97.89% (93/95), respectively. ORR for the 1^st line usage was 63.77% (44/69), while this for ≥2^nd line was 42.31% (11/26) (p = 0.059). For those with NGS data, the most common fusion partners were EML4 (41/50, 82.0%), and KIF5B (3/50, 6.0%), while we also identified rare partners including HIP1, STRN, WDPCP, LSAMP, SGMS1, and KCNG4, and the last three have never been reported. Cases with concomitant genomic mutations indicated a worse ORR than pure ALK fusion cases (7/18, 38.89% vs. 22/32, 68.75%, p = 0.04). TP53 mutation was the most common co-existing alterations (9/50, 18.0%). Concomitant TP53 mutations showed a trend toward a lower ORR than those without TP53 mutations (4/9, 44.44% vs. 25/41, 60.98%, p = 0.293). 84.21% (80/95) cases experienced no adverse effects (AEs), while only 2 had grade 3 (edema) and 12 suffered from grade 1∼2 AEs (abnormal liver or renal functions, rash and constipation).

Conclusions

Our study demonstrated that alectinib was an effective and tolerable inhibitor in ALK-rearranged NSCLC patients. Concomitant alterations may dampen the response of alectinib, indicating that improved stratification based on NGS findings may optimize the benefit.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.