3425 - Safety and Dose-Limiting Toxicities of Concurrent Radiotherapy with Tarlatamab in Relapsed/Refractory Small Cell Lung Cancer: A Single Institution Retrospective Analysis
Presenter(s)
S. K. Attia1, R. K. Kyasaram2, T. Arsenault1, T. Slater3, A. Dowlati4, M. Hsu5, L. Chiec3, M. Mirsky6, D. E. Spratt7, H. K. Perlow1, P. Mohindra1, and A. Baydoun1,8; 1Department of Radiation Oncology, University Hospitals Cleveland Medical Center/ Seidman Cancer Center, Cleveland, OH, 2University Hospitals Seidman Cnacer Center, Cleveland, OH, 3Case Western Reserve University School of Medicine, Cleveland, OH, 4Department of Medical Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, 5Department of Medical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, 6Case Western Reserve University-University Hospitals Seidman Cancer Center, Cleveland, OH, 7University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, 8Case Western Reserve University, Cleveland, OH
Purpose/Objective(s):
Tarlatamab, a bispecific DLL3×CD3 T-cell engager approved for relapsed/refractory small cell lung cancer (SCLC), is increasingly used in clinical practice. Palliative and consolidative radiotherapy (RT) is frequently co-administered in this population, yet safety data on concurrent RT during tarlatamab are lacking. We aimed to evaluate whether concurrent RT would be tolerable without unacceptable toxicity or tarlatamab dose reductions.Materials/Methods:
This retrospective analysis included 35 patients with relapsed/refractory SCLC who received at least one tarlatamab dose between 2021–2025, comparing those receiving concurrent RT versus tarlatamab alone. Concurrent RT was defined as any course initiated within 7 days before tarlatamab cycle 1, day 1 or during active treatment. Toxicities were graded per CTCAE v5.0. The primary endpoint was incidence of dose-limiting toxicity (DLT), defined as Grade =3 non-hematologic adverse event within 60 days of RT initiation. Overall survival (OS) was estimated by Kaplan-Meier with log-rank group comparison.Results:
Of the total 35 patients, thirteen (37%) received concurrent RT (31 courses; median 1/patient, range 1–9) while 22 (63%) received tarlatamab alone. Median age was 68 years (IQR 63–73); 51% female; 86% former smokers; ECOG PS 0–1 in 62%. Brain metastases were present in 77% overall and 92% of RT patients. Concurrent RT was predominantly intracranial (23/31 courses, 74%): 20 brain SRS courses and 3 whole-brain RT (WBRT). Extracranial RT included lung/mediastinum (n=3), spine (n=2), and abdomen/pelvis (n=3); dose range 8–30 Gy/1-10 fractions across all sites. Median RT initiation was Day 22 from C1D1 (range 3–618). Grade =2 adverse events occurred in 4/13 (31%) RT patients. Predominant terms were pain, fatigue, and dyspnea. DLT rate was 1/13 (7.7%; 95% CI 0.2–36.0%), representing Grade 3 fatigue following spine RT. No Grade 4–5 events occurred. Two RT patients required temporary tarlatamab holds; no dose reductions were needed. Median OS was 10.0 months (6-month: 57.4%; 12-month: 46.3%). The RT group demonstrated numerically longer OS but not significantly different (12.7 vs. 5.5 months; log-rank p=0.112)Conclusion:
Pending ongoing prospective clinical trial, early retrospective data from our institution suggests that concurrent RT during tarlatamab is feasible and no dose reductions are required| Characteristic | RT (n = 13) | No RT (n = 22) | Total (N = 35) |
| Age, median (range), yrs | 66 (61–82) | 68 (48–81) | 67 (48–82) |
| Female sex, n (%) | 8 (62%) | 10 (45%) | 18 (51%) |
| ECOG PS 0–1, n/N evaluable (%) | 6/10 (60%) | 12/19 (63%) | 18/29 (62%) |
| Brain metastases, n (%) | 12/13 (92%) | 15/22 (68%)a | 27/35 (77%) |
| COPD, n/N evaluable (%) | 7/7 (100%) | 16/16 (100%) | 23/23 (100%) |
| Baseline supplemental O2, n/N evaluable (%) | 7/13 (54%) | 10/22 (45%) | 17/35 (49%) |
| Prior platinum/etoposide, n/N evaluable (%) | 11/13 (85%) | 21/22 (95%) | 32/35 (91%) |
| Prior immunotherapy, n/N evaluable (%) | 11/13 (85%) | 17/22 (77%) | 28/35 (80%) |
| Prior RT, n/N evaluable (%) | 8/13 (62%) | 22/22 (100%) | 30/35 (86%) |