% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Zhou:278582, author = {X. Zhou and L. Zhou and Z. Yao and M. Huang and Y. Gong and B. Zou and J. Zhu and Y. Liu and F. Peng and Y. Zhang and M. Yu and Y. Li and F. Na and Y. Wu and K. Kang and W. Xiu and X. Zhang and L. Zhou and Y. Xu and J. Wang and Y. Wang and X. Yang and Y. Wu and R. Li and Y. Zhang and Z. Yang and Z. Zhou and J. Bai and X. Yi and R. Tong and L. Yin and C. Chen and G. Niedermann$^*$ and Y. Lu and J. Xue}, title = {{S}afety and {T}olerability of {L}ow-{D}ose {R}adiation and {S}tereotactic {B}ody {R}adiotherapy + {S}intilimab for {T}reatment-{N}aive {S}tage {IV} {PD}-{L}1+ {N}on-{S}mall-{C}ell {L}ung {C}ancer {P}atients.}, journal = {Clinical cancer research}, volume = {29}, number = {20}, issn = {1078-0432}, address = {Philadelphia, Pa. [u.a.]}, publisher = {AACR}, reportid = {DKFZ-2023-01663}, pages = {4098-4108}, year = {2023}, note = {2023 Oct 13;29(20):4098-4108}, abstract = {Low-dose radiation therapy (LDRT) may enhance the synergistic anti-tumor effect of combined immunotherapy and stereotactic body radiation therapy (SBRT). The safety and efficacy of this novel triple-combination therapy were evaluated for the first time as first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC).This prospective phase 1 study enrolled 29 patients and included a dose-escalation and dose-expansion phase. Patients received SBRT (30 Gy/3f) to small lesions and LDRT (2 Gy/1f, 4 Gy/2f, or 10 Gy/5f) to a large lesion concurrently, followed by sintilimab (a PD-1 inhibitor). The primary endpoint was safety and tolerability; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).No dose-limiting toxicities were observed during the dose-escalation phase; 4 Gy/2f was the recommended LDRT dose. Median follow-up was 15.6 months. Treatment-related adverse events (TRAEs) occurred in $96.6\%$ (28/29) of patients (grade ≥ 3, $20.7\%$ [6/29]); two patients $(6.9\%)$ discontinued due to TRAEs. Seven patients experienced pneumonitis (grade 2, n = 6; grade 3, n = 1). Immune-related adverse events were noted in $58.6\%$ (17/29) of patients. In patients with tumor assessment (n = 28), ORR and confirmed ORR were $60.7\%$ and $57.1\%,$ respectively. Median PFS was 8.6 months $(95\%$ confidence interval 3.7-16.5), and median OS was not reached. Exploratory analyses suggested both expanded and newly emerging TCR clonotypes were associated with better PFS.The findings indicate that the novel SBRT + LDRT + sintilimab therapy is safe and promising in patients with PD-L1-positive, driver gene-negative primary metastatic NSCLC.}, cin = {FR01}, ddc = {610}, cid = {I:(DE-He78)FR01-20160331}, pnm = {899 - ohne Topic (POF4-899)}, pid = {G:(DE-HGF)POF4-899}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:37581611}, doi = {10.1158/1078-0432.CCR-23-0315}, url = {https://inrepo02.dkfz.de/record/278582}, }