Penpulimab and Anlotinib in PDL1 High-expression Pulmonary Giant Cell Carcinoma with Cerebral Metastases: Case Report and Review

Overview

Journal Front Oncol

Specialty Oncology

Date 2025 Jan 7

PMID 39763602

Authors

MingHong Xie

Yunlong Zhao

Xiaohua Hou

Ning Li

Sha Niu

Xinju Xu

Affiliations

Soon will be listed here.

Abstract

Pulmonary giant cell carcinoma (PGCC) is a rare subtype of non-small cell lung cancer (NSCLC) characterized by complex pathology, high rates of misdiagnosis or missed diagnosis, an aggressive clinical course, rapid progression, and poor prognosis. This case report describes a 67-year-old Chinese male with a left upper lobe lung mass, diagnosed CT-guided lung biopsy as PGCC with symptomatic multiple cerebral metastases. The tumor showed strong PD-L1 positivity, and genetic testing revealed a TP53 exon 4 c.313G mutation. Treatment involved first-line therapy with Penpulimab injection combined with Anlotinib and concurrent cranial radiotherapy. Significant reduction in both the pulmonary and cerebral metastatic lesions was observed, with notable efficacy. As of June 2024, there has been no disease progression for 26 months, with the patient currently maintained on Anlotinib monotherapy. This case demonstrates the favorable efficacy of Penpulimab injection combined with Anlotinib in treating advanced PGCC. These findings indicate that this combination therapy may offer a promising new therapeutic option for this rare type of lung cancer.

References

Singh Achrol A, Rennert R, Anders C, Soffietti R, Ahluwalia M, Nayak L . Brain metastases. Nat Rev Dis Primers. 2019; 5(1):5. DOI: 10.1038/s41572-018-0055-y. View

Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K . Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020; 21(10):1353-1365. DOI: 10.1016/S1470-2045(20)30445-9. View

Maneenil K, Xue Z, Liu M, Boland J, Wu F, Stoddard S . Sarcomatoid Carcinoma of the Lung: The Mayo Clinic Experience in 127 Patients. Clin Lung Cancer. 2018; 19(3):e323-e333. DOI: 10.1016/j.cllc.2017.12.008. View

Le Rhun E, Guckenberger M, Smits M, Dummer R, Bachelot T, Sahm F . EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours. Ann Oncol. 2021; 32(11):1332-1347. DOI: 10.1016/j.annonc.2021.07.016. View

Rini B, Plimack E, Stus V, Gafanov R, Hawkins R, Nosov D . Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019; 380(12):1116-1127. DOI: 10.1056/NEJMoa1816714. View

Reck M, Rodriguez-Abreu D, Robinson A, Hui R, Csoszi T, Fulop A . Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016; 375(19):1823-1833. DOI: 10.1056/NEJMoa1606774. View

Yu L, Xu J, Qiao R, Han B, Zhong H, Zhong R . Efficacy and safety of anlotinib combined with PD-1/PD-L1 inhibitors as second-line and subsequent therapy in advanced small-cell lung cancer. Cancer Med. 2022; 12(5):5372-5383. PMC: 10028028. DOI: 10.1002/cam4.5360. View

Scoccianti S, Olmetto E, Pinzi V, Osti M, Di Franco R, Caini S . Immunotherapy in association with stereotactic radiotherapy for non-small cell lung cancer brain metastases: results from a multicentric retrospective study on behalf of AIRO. Neuro Oncol. 2021; 23(10):1750-1764. PMC: 8485442. DOI: 10.1093/neuonc/noab129. View

Vieira T, Girard N, Ung M, Monnet I, Cazes A, Bonnette P . Efficacy of first-line chemotherapy in patients with advanced lung sarcomatoid carcinoma. J Thorac Oncol. 2014; 8(12):1574-7. DOI: 10.1097/01.JTO.0000437008.00554.90. View

10.

Yang S, Zhang W, Chen Q, Guo Q . Clinical Investigation of the Efficacy and Safety of Anlotinib with Immunotherapy in Advanced Non-Small Cell Lung Cancer as Third-Line Therapy: A Retrospective Study. Cancer Manag Res. 2020; 12:10333-10340. PMC: 7585515. DOI: 10.2147/CMAR.S280096. View

11.

Xia C, Dong X, Li H, Cao M, Sun D, He S . Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022; 135(5):584-590. PMC: 8920425. DOI: 10.1097/CM9.0000000000002108. View

12.

Zheng Y, Zhu J, Xiong J, Jiang O, Wang H, Xie Y . Phase 1b/2 study of penpulimab (AK105), an antiprogrammed cell death-1 immunoglobulin G1 antibody, in advanced or metastatic solid tumors (AK105-204). Cancer. 2024; 130(12):2180-2190. DOI: 10.1002/cncr.35259. View

13.

Han C, Ye S, Hu C, Shen L, Qin Q, Bai Y . Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203). Front Oncol. 2021; 11:684867. PMC: 8313824. DOI: 10.3389/fonc.2021.684867. View

14.

Chu T, Zhong R, Zhong H, Zhang B, Zhang W, Shi C . Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC. J Thorac Oncol. 2021; 16(4):643-652. DOI: 10.1016/j.jtho.2020.11.026. View

15.

Joshi H, Bhanot G, Borresen-Dale A, Kristensen V . Potential tumorigenic programs associated with TP53 mutation status reveal role of VEGF pathway. Br J Cancer. 2012; 107(10):1722-8. PMC: 3493873. DOI: 10.1038/bjc.2012.461. View

16.

Hu H, Xu Z, Zhu Q, Liu X, Jiang S, Zheng J . Brain Metastases Status and Immunotherapy Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis. Front Immunol. 2021; 12:669398. PMC: 8316922. DOI: 10.3389/fimmu.2021.669398. View

17.

Xie L, Xu J, Sun X, Guo W, Gu J, Liu K . Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial. J Immunother Cancer. 2020; 8(1). PMC: 7223462. DOI: 10.1136/jitc-2020-000798. View

18.

Crino L, Bronte G, Bidoli P, Cravero P, Minenza E, Cortesi E . Nivolumab and brain metastases in patients with advanced non-squamous non-small cell lung cancer. Lung Cancer. 2019; 129:35-40. DOI: 10.1016/j.lungcan.2018.12.025. View

19.

Huang Y, Kim B, Chan C, Hahn S, Weissman I, Jiang W . Improving immune-vascular crosstalk for cancer immunotherapy. Nat Rev Immunol. 2018; 18(3):195-203. PMC: 5922422. DOI: 10.1038/nri.2017.145. View

20.

Chen J, Xiao Y, Cai X, Liu J, Chen K, Zhang X . Overexpression of p53R2 is associated with poor prognosis in lung sarcomatoid carcinoma. BMC Cancer. 2017; 17(1):855. PMC: 5731091. DOI: 10.1186/s12885-017-3811-6. View