Effect of durvalumab in patients with unresectable stage 3 non–small cell lung cancer post-chemoradiotherapy.

Abstract

8550 Background: The PACIFIC study (PS) concluded that the use of durvalumab from 1 to 42 days after concurrent chemoradiotherapy (CXRT) in stage 3 unresectable non-small cell lung cancer (NSCLC) increased the median overall survival (mOS) from 29 to 48 months. It also showed a benefit in tumors with PD-L1 <25%. However, a post-hoc analysis of the PS showed no survival benefit with durvalumab in patients with PD-L1 <1% but was not statistically powered. Currently in the US, durvalumab is approved irrespective of PDL-1 percentage, whereas in Europe it is not approved for tumors with PDL-1 <1%. Also, there was no survival benefit in starting durvalumab within and after 2 weeks of CXRT. Our objectives in this study are to analyze the impact of PDL-1 expression and the date of initiation of durvalumab post CXRT on mOS. Methods: We conducted a retrospective observational study of stage 3 unresectable NSCLC patients who received durvalumab post CXRT at LSU Health Shreveport from 2018 to 2021. A survival analysis was done including the following variables: age, race, sex, tumor histology, tumor PD-L1 percentage, and date of initiation of durvalumab post CXRT. P-value <0.05 was considered statistically significant. Results: We identified 83 patients who received durvalumab after CXRT for treatment of stage 3 unresectable NSCLC. Baseline characteristics are provided in table 1. Among all the tumors, 25% had a PDL-1 <1%. 33% of the study population received durvalumab less than 30 days after CXRT and 67% received it after 30 days. The mOS was not impacted by race, sex, or tumor hisotology. Compared to higher PDL-1 percentage, patients with PD-L1 <1% had a statistically significant lower survival probability. At 14 months, 87% of patients with a PD-L1 <1% were alive compared to 100% in those with a PD-L1 1-50% or a PD-L1 >50%. Less than 35% of patients with PD-L1 <1% survived beyond 30 months compared to 45% for PD-L1 1-50% and 100% for PD-L1 >50% (p-value 0.02). Patients who received durvalumab 30-60 days after concurrent CXRT had a lower OS at 30 months compared to those who started before 30 days (44% versus 90%). However, statistical significance was not reached (p-value 0.45). Conclusions: This study demonstrates that patients with a PD-L1 tumor expression of <1% had a statistically significant lower survival probability compared to those with a PD-L1 expression of 1-50% and > 50% in this patient population. Time from CXRT to the start of durvalumab was not shown to affect survival outcomes.[Table: see text]

Induction immunochemotherapy followed by definitive chemoradiotherapy for unresectable locally advanced non‐small cell lung cancer: a multi‐institutional retrospective cohort study

“…In subgroup analyses, the PACIFIC trial indicated limited benefit from durvalumab consolidation in patients with PD‐L1 expression below 25% and even lesser effectiveness for those with PD‐L1 under 1% 6 . This finding is consistent with a 2022 ASCO study indicating reduced survival in stage III unresectable NSCLC patients with PD‐L1 under 1% after concurrent CRT 28 . Our study found notably higher ORR and OS in patients with over 50% PD‐L1 expression, while those with less than 1% showed poorer outcomes, albeit not statistically significant.…”

“…6 This finding is consistent with a 2022 ASCO study indicating reduced survival in stage III unresectable NSCLC patients with PD-L1 under 1% after concurrent CRT. 28 Our study found notably higher ORR and OS in patients with over 50% PD-L1 expression, while those with less than 1% showed poorer outcomes, albeit not statistically significant. These findings highlight the need for PD-L1 level-based personalized treatments.…”

Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations

“…Subgroup analysis of the PACIFIC study showed that receiving ICIs within 0–14 days after the end of cCRT correlated with better PFS and OS than patients receiving ICIs between 15–42 days [ 9 ]. Similarly, a retrospective observational study of patients with stage III unresectable NSCLC who received durvalumab after cCRT from 2018 to 2021 was recently reported; patients who received durvalumab 30–60 days after cCRT had lower OS rate at 30 months compared to those who started durvalumab before 30 days (44% vs. 90%) [ 135 ]. However, this difference was not statistically significant ( P = 0.45).…”

“…The PACIFIC-R trial supported the feasibility of durvalumab in PD-L1-negative tumors, however, the median PFS was indeed shorter than PD-L1 ⩾1% tumors [ 51 ]. The abstract 8550 posted in ASCO 2022 demonstrated that patients with tumoral PD-L1 expression of < 1% had a significantly lower survival probability, compared to those of 1–50% and > 50% in patients with stage III unresectable NSCLC who received durvalumab post cCRT [ 135 ]. Low PD-L1 expression may originate from a lack of tumor infiltrating lymphocytes (TIL) and expression of other co-inhibitory checkpoints; therefore, strategies with dual checkpoint blockade consolidation are expected.…”