Association of Molecular Profiles and Mutational Status With Distinct Histological Lung Adenocarcinoma Subtypes. An Analysis of the LACE-Bio Data

Can Molecular Biomarkers be Utilized to Determine Appropriate Adjuvant Therapy in Early-Stage Non-Small Cell Lung Cancer (NSCLC)?

“…This involved 4,584 patients and showed that adjuvant chemotherapy use had an Overall Survival (OS) advantage of 5.4% [ 5 ]. Data from these 1990s studies have stood the test of time and is utilized in clinical practice even today [ 6 ]. For tumors >3 cms that have an EGFR exon 19 deletion or exon 21 L858R mutation, data from ADAURA has shown that using Osimertinib 80 mg Daily for 3 years improved overall survival by 10% [ 7 ].…”

“…This shift underscores an effort to select patients who stand to benefit most from specific drug classes while minimizing exposure to the potential toxicity of unnecessary systemic therapy [ 1 ]. With this context, the LACE Bio investigators recapitulated and re-reviewed the legacy LACE Bio data, to look at the molecular and biomarker correlation for adjuvant chemotherapy benefit [ 6 ]. The LACE bio group looked at the molecular profiles of the samples from the International Adjuvant Lung Trial, Cancer, and Leukemia Group B–9633, and National Cancer Institute of Canada Clinical Trials Group JBR.10.…”

“…The LACE bio group looked at the molecular profiles of the samples from the International Adjuvant Lung Trial, Cancer, and Leukemia Group B–9633, and National Cancer Institute of Canada Clinical Trials Group JBR.10. Samples from the Adjuvant Navelbine International Trialist Association (ANITA) trial was not available [ 6 ]. A cohort of 357 patients with adenocarcinoma were utilized to perform analysis of groups assigned based on molecular determinants.…”

“…When TMB was ≥ 10, OS with adjuvant chemotherapy use was 2.75 times worse than without it (2.75, 95% Confidence Interval (CI): 1.07–7.04, p=0.035). It has been hypothesized that this group could potentially be a cohort who may be able to forego chemotherapy and may benefit from ICI alone [ 6 ]. It was also noted that the marked TILs/low TMB group had a benefit for DFS (HR = 0.06, 95%CI: 0.01–0.53) with adjuvant chemotherapy use, that supported the theory, but the marked TILs cohort was relatively small in the study (26/357).…”

“…It was also noted that the marked TILs/low TMB group had a benefit for DFS (HR = 0.06, 95%CI: 0.01–0.53) with adjuvant chemotherapy use, that supported the theory, but the marked TILs cohort was relatively small in the study (26/357). Although these results do not change clinical practice at this time due to the obvious limitations of the study (retrospective nature, small subset analysis, and older techniques to measure PD-L1), it does put forth a possibility of identifying a group of patients who may be able to forego systemic adjuvant chemotherapy [ 6 ].…”