Authors: Jacob Sands1, Liangliang Zhang2, Alexa Schrock2, Geoffrey Oxnard2
1Dana-Farber Cancer Institute 2Foundation Medicine, Inc.
BACKGROUND: The 2-year mark has become a new milestone in pts with aNSCLC receiving immunotherapy. In pts who are progression free at that point, a subset experience ongoing disease control even after stopping active treatment. Some pts experience such impressive durability beyond 2 years, raising a question about potential cure. We queried a real-world (RW) clinico-genomic database (CGDB) to better understand these pts with durable benefit and their clinical and genomic features.
METHODS: Using the nationwide (~280 US cancer clinics) de-identified EHR-derived Flatiron Health-Foundation Medicine aNSCLC clinico-genomic database (CGDB) linked to genomic data, pts treated with ICI (+/- chemotherapy) from 01/2011-06/2021 were selected. RW progression (rwP) was obtained via technology-enabled abstraction of EHR data. Durable benefit was classified as absence of rwP, death or treatment failure (indicated by switch to a new line of therapy) within 24 mos of beginning ICI therapy.
RESULTS: In a cohort of 4,030evaluable aNSCLC pts, 184 (4.6%) were free of rw P or treatment failure at 24 mos. Of these 184 pts with durable benefit,84% received ICI monotherapy and16% received ICI with chemotherapy; ICI treatment was more often first line (1L, 43%) or 2L (38%). 59% with durable benefit were still on ICI at the 2-year mark, whereas 41% had stopped a median of 11.4 mos after therapy start. Of 109pts remaining on ICI for 2-years, median time on ICI was 36.3 mos from therapy start. Overall, pts with durable benefit had a median rw PFS of 37.1 mos and median rw OS of 58.8 mos from start of ICI. Compared to pts with rw P on ICI before 24 mos, those with durable benefit were more likely to have history of smoking (94% vs 86%) and absence of liver, brain or bone metastases (all p<0.001).High tumor mutational burden (TMB ≥10)was more common (62% vs 35%, p <0.001) andSTK11, CDKN2B, PIK3CA, and EGFR alterations were less common in pts with durable-benefit vs those with rw P on ICI before 24 mos. In a multivariate cox model of rw PFS beyond 24 mos in pts with durable benefit, TMB ≥20 was significantly associated with longer rw PFS (HR 0.45 95% CI 0.24-0.83, p =0.01) while TMB ≥10 was marginally significant (HR0.65 95% CI 0.40-1.03, p=0.07); treatment with ICI with chemotherapy was significantly associated with worse rw PFS (HR 1.84 95% 1.093.12, p =0.02).High PD-L1 >50% was noted in 728 (19%) of those without durable benefit and 38 (21%) of those with durable benefit, though many in the data set had unknown PD-L1 status.
CONCLUSION: Pts with durable benefit >2 years after starting ICI therapy for aNSCLC represent a unique population of immune survivors with a median OS of almost 5 years;41% of pts stopped ICI before the2-year mark. Elevated TMB was associated with durable benefit on ICI as well as prolonged rwPFS after the 2-year mark and deserves further investigation as a biomarker for prolonged benefit to ICI in aNSCLC.
This research was originally presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Read more on ASCO.org.