MA19.02 Prior Therapy and Increased Expression of PD-L1 in NSCLC Tumor Samples

Tumor PD-L1 expression has been shown to enrich for response to immunotherapy in several indications, including advanced NSCLC. However, the stability of PD-L1 expression over time and its relationship with non-immunotherapy cancer treatment is currently uncertain. We hypothesized that prior chemotherapy or radiotherapy would increase PD-L1 expression. In the Phase 2, open-label, single-arm durvalumab ATLANTIC study (NCT02087423), patients who had received ≥2 prior systemic regimens in the treatment of Stage IIIB or IV NSCLC were screened for tumor PD-L1 expression by immunohistochemistry using the VENTANA PD-L1 (SP263) Assay (25% tumor cell [TC] cutoff). PD-L1 expression was assessed using either a recent (<3 months) or archival sample; a subset of patients provided both. The relationship between non-immunotherapy cancer treatment and prevalence of tumor PD-L1 expression ≥25% (TC≥25%) was assessed in patients who received therapy prior to sample acquisition versus those who did not. Pearson’s chi-squared test was used to examine the differences between patient subgroups. Of the patients screened for participation in ATLANTIC, 1590 were successfully assessed for PD-L1 expression. PD-L1 TC≥25% prevalence was higher in patients who had received prior radiotherapy or chemotherapy before sample acquisition, with prevalence noticeably higher in those who had received ≥2 lines of prior chemotherapy. Prior EGFR inhibitor treatment did not have any noticeable relationship to TC≥25% prevalence (Table). In the subset of patients with paired recent and archival samples, TC≥25% prevalence remained the same in 74% of cases, increased over time in 19.5%, and decreased in 6.5%. PD-L1 expression may increase in response to chemotherapy or radiotherapy and is unlikely to decrease over time. Re-biopsy may provide a more accurate assessment of current tumor PD-L1 expression status when a low/negative result is seen in an archival sample, particularly if the patient has received multiple lines of intervening radiotherapy or chemotherapy.