Anlotinib combined with durvalumab in a patient with recurrent multifocal brain metastases of small cell lung cancer after definitive concurrent chemoradiotherapy and palliative radiotherapy of the lung and brain: a case report

Abstract

The brain is a common metastatic site of small cell lung cancer (SCLC), but systematic treatment options are limited by the blood-brain barrier. Currently, the optimal treatment regimen remains controversial, especially for patients already treated by brain radiotherapy. Anlotinib is a novel oral multitarget tyrosine kinase inhibitor which has shown significant improvement in progression-free survival and overall survival in third-line or beyond therapy of advanced SCLC in a randomized, double-blind phase II study (ALTER1202 trial) based on a Chinese population sample. Emerging data has also suggested that immunotherapy, such as the programmed death ligand 1 (PD-L1) inhibitor, has a relatively high response rate in brain metastatic SCLC, although there is a lack of large sample-size studies. Integrating anlotinib and immunotherapy for recurrent or relapsing brain metastases (BMs) of SCLC has not been previously reported, but it is possible that these two treatments may have synergistic effects and provide even better outcomes. Here, we present a case of stage III SCLC who developed lung and BMs after concurrent chemoradiotherapy (cCRT) and achieved radiographic locally complete regression following whole brain irradiation (WBI) with a simultaneous integrated boost (SIB) technique. Durvalumab was delivered as maintenance therapy. Asymptomatic multifocal recurrence of BMs occurred after the administration of the second dose of durvalumab. After administration of combined durvalumab and anlotinib, the BMs achieved near-complete regression and no severe toxicity was reported. This suggests a potential synergistic effect of combined durvalumab and anlotinib in previously treated BMs in a patient with SCLC and may provide a direction for future clinical decisions.

Treatment of Small Cell Lung Cancer patients with brain metastases shows promise with the combination therapy of Cardonilumab and Anlotinib

“…It signi cantly enhanced PFS (3.8 vs 0.8 months, P = 0.001) and OS (6.1 vs 2.6 months, P = 0.006) when used as a third-line or subsequent treatment, surpassing the effectiveness of placebo [7].The clinical potential of using anlotinib in combination with ICIs for treating patients with BM is promising.According to our research, approximately half (50%) of patients with detectable CNS lesions exhibited a positive response within the brain, and the average overall survival (OS) was 19.3 months, surpassing the effectiveness of each individual treatment.Based on a case report, the combination of anlotinib and durvalumab, a PD-L1 inhibitor, resulted in almost complete disappearance of SCLC brain lesions. This aligns with our discovery that remarkable effectiveness in the brain can be attained by using ICIs along with anlotinib [24].The combination of treatments can have a synergistic impact because Anlotinib may enhance the in ltration of innate immune cells and promote vessel normalization, thereby altering the immunosuppressive tumor microenvironment and enhancing the effectiveness of immune checkpoint inhibitors.…”

Immunotherapy: an emerging modality to checkmate brain metastasis

“…Another seven cycles of this treatment regimen were given with sustained complete response [ 124 ]. Wu et al present a similar case report with a patient who had stage-III SCLC and developed BrM after concurrent chemotherapy and WBRT [ 125 ]. Durvalumab, a PD-L1 antibody, was used as maintenance therapy [ 125 ].…”

“…Wu et al present a similar case report with a patient who had stage-III SCLC and developed BrM after concurrent chemotherapy and WBRT [ 125 ]. Durvalumab, a PD-L1 antibody, was used as maintenance therapy [ 125 ]. Treatment failure occurred with the multifocal reoccurrence of BrM after the second dose of durvalumab [ 125 ].…”

“…Durvalumab, a PD-L1 antibody, was used as maintenance therapy [ 125 ]. Treatment failure occurred with the multifocal reoccurrence of BrM after the second dose of durvalumab [ 125 ]. After administration of anlotinib along with durvalumab, near complete regression of BrM was achieved, with no severe toxicity reported [ 125 ].…”

“…Treatment failure occurred with the multifocal reoccurrence of BrM after the second dose of durvalumab [ 125 ]. After administration of anlotinib along with durvalumab, near complete regression of BrM was achieved, with no severe toxicity reported [ 125 ]. These case reports suggest that failure of one PD-1/PD-L1 inhibitor does not indicate failure of IT altogether and that it is still possible to continue treatment with the same or different PD-1/PD-L1 inhibitor with treatment success.…”