Dartmouth-Hitchcock Medical Center, Lebanon, NH
Yuanzhen Cao , Muhammad Zubair Afzal , Ziyao Lu , Aditya Sharma , Jonathan P. Pirruccello , Keisuke Shirai
Background: Immune checkpoint inhibitors (ICIs) have proven successful in treating extensive stage small-cell lung cancer (ES-SCLC). Atezolizumab, a PD-L1 inhibitor, is approved as first-line therapy for ES-SCLC in combination with chemotherapy. SCLC has a high incidence to spread to the brain with more than 50% of patients developing brain metastases (BM) during their clinical course. However, patients with BM have frequently been excluded from clinical trials due to their perceived poor prognosis. This study aimed to assess the efficacy of ICI in achieving disease response and managing intracranial disease in patients with ES-SCLC. Methods: We conducted a retrospective study on patients with biopsy-confirmed ES-SCLC treated with at least one cycle of atezolizumab/carboplatin/etoposide combination from 2015 to 2022. Overall survival (OS), progression-free survival (PFS) and radiographic response were noted in patients with and without BM. Intracranial (IC) response was documented in patients with radiographic evidence of BM who had at least one follow-up brain imaging after the start of ICI. Results: A total of 83 patients were included, 39.3% (n = 33) of which had BM. Median follow-up was 8 (95%CI: 4.5-11.6) months. Baseline characteristics were summarized in the table below. Disease progression occurred in 90.9% patients with BM and death in 51.5%. Among 21 patients who fulfilled IC response assessment criteria, one (4.8%) had complete response, four (19.0%) had partial response, two (9.5%) had stable disease and fourteen (66.7%) had disease progression. Median duration of IC response was 5.3 (95%CI: 0.00-20.35) months; IC objective response rate was 23.8%. No difference was found in OS (10 vs. 30 months, P = 0.3) or PFS (6 vs. 7 months, P = 0.18) in patients with and without BM respectively. Patients with > 3 BM (n = 16) had inferior OS (7 vs. 21 months, P = 0.01) and PFS (5 vs. 6 months, P = 0.002) compared to those with ≤3 BM. Conclusions: This study demonstrated that ICI achieved similar outcomes in patients with and without BM and produced meaningful intracranial response in patients with BM. Therefore, further clinical trials on ES-SCLC should encompass patients with BM, especially those with ≤3 BM. Future research on a larger, more diverse patient population is warranted.
Patient characteristics | Total patients without BM (n = 50) | Total patients with BM (n = 33) | |
---|---|---|---|
Age | median | 69.5 | 68 |
range | 42-85 | 58-84 | |
Gender (M) | 66% | 54.5% | |
Race (Caucasian) | 98% | 100% | |
ECOG (0-1) | 72% | 63.6% | |
Smoking status | Current | 72% | 63.6% |
Former | 26% | 36.3% | |
Never | 2% | 0% | |
Stage at diagnosis (extensive) | 80% | 100% | |
Cycle of ICI | Mean | 6.6 | 7.2 |
range | 1-14 | 1-37 | |
Prior systemic therapies | 9.1% | ||
Prior CNS therapies | 9.1% | ||
BM at diagnosis | 57.6% | ||
Presence of neurological symptoms | 66.7% | ||
Size of largest BM (mm) | median | 13 | |
range | 3-34 | ||
> 3 BM | 48.4% | ||
Steroid use ( > 10 days) | 72.7% |
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