The prognostic impact of TP53 mutation on survival outcomes in ALK fusion–positive lung cancer.

Abstract

e20651 Background: Patients with advanced anaplastic lymphoma kinase (ALK) rearranged lung adenocarcinoma have better survival outcomes when treated with ALK inhibitors (ALKi). However, the presence of non-driver co-mutations have a negative prognostic impact. Subset analysis of the phase-III CROWN trial showed a negative prognostic impact in patients with concomitant Tumor Protein 53 (TP53) mutation. We explored the impact of concomitant TP53 mutation in ALK rearranged lung cancer patients treated at our institute. Methods: This was a retrospective, single-centre, observational study conducted at our institute from January 2018 to November 2023. Treatment-naïve ALK rearranged lung cancer patients planned for systemic treatment were eligible. Mutations were identified by Next Generation Sequencing (NGS) done on the pre-treatment tissue biopsy or circulating-tumor DNA in blood samples. We assessed pre-treatment patient demographics, the results of genomic sequencing, treatment patterns, and survival outcomes [progression-free (PFS) and overall survival (OS)] in our patients. Results: The data of 86 consecutive patients was analysed. The median age of the cohort was 51 years (IQR, 43-57), 58.1% (n=50) were males, 82.6% (n=71) were non-smokers, and 94.2% (n=81) had an adenocarcinoma histology. Advanced stage disease was seen in 93.0% (n=80) patients, with lung (68.6%, n=59) and non-regional lymph nodes (69.8%, n=60) being the most common sites of distant metastasis. Tissue-based NGS testing was done in 98.9% (n=85) patients, and 96.4% (n=81/84) NGS panels assessed >50 genes. TP53 co-mutation was seen in 15.1% (n=13) cases, while the presence of any non-driver co-mutation was seen in 26.7% (n=23) cases. Patients treated with ALKi in any treatment line, were 83.7% (n=72). Crizotinib was the most commonly used ALKi (58.1%, n=50), while ceritinib, alectinib, and lorlatinib were used in 9.3% (n=8), 17.4% (n=15), and 15.1% (n=13) patients respectively. The median follow-up and median OS of the cohort was 30.7 months (95%CI, 26.2-35.2), and 51.3 months (95%CI, 42.3-60.2) respectively. In patients with a TP53 co-mutation, the median OS was 23.7 months (95%CI, 12.5-34.9) versus 55.0 months (95%CI, 45.4-64.6, p=0.022) in those without TP53 mutation. A trend towards shorter survival was seen irrespective of the generation of ALKi used. Conclusions: TP53 co-mutation has a negative prognostic impact in patients with ALK rearranged lung cancer. Studies evaluating fourth generation ALKi, or the addition of chemotherapy in these patients are warranted.