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Immunotherapy delivers amazing results
Brain metastases (BM) are very common in non-small cell lung cancer (NSCLC) and the prognosis is quite poor, with median survival of less than 6 months in treatment-naïve patients. The mainstay of treatment for patients with NSCLC and BM is surgical resection and radiation therapy (RT) (category 2A recommended evidence), but the risk of neurotoxicity is as high as 35 percent [1].
Immunotherapy (or combination chemotherapy) has become an important approach to the treatment of NSCLC, and while there have been many clinical trials of PD-1 monoclonal antibodies for the treatment of patients with metastatic NSCLC, most have excluded these patients with untreated BM.
How to choose treatment for NSCLC patients with BM who are not treated? This issue of Oncology Channel brings a miracle case of NSCLC complicated with BM that was in complete remission after fourth-line therapy.
Medical records
The patient is a 60-year-old male
Chief complaint: recurrent cough and sputum for more than several months
The cardiopulmonary physical examination is normal, and he smokes for 40 packs a year.
CT：右侧肺中叶肿块（2.7 cm×2.1 cm），右侧下肺门转移（5.0 cm×6.2 cm），伴纵隔淋巴结肿大。
纵隔淋巴结活检：肺腺癌，CK7(+)、TTF1(+)和Napsin A(+)
MRI: multiple lacunar brain injury in the frontoparial lobe
免疫组化：PD-L1＞95%，
基因检测：EGFR(-)、ROS1(-)、ALK(-)、BRAF(-)、C-MET(-)
临床诊断：NSCLC IIIB期（T4N2M0）
ECOG score: 1 point
Diagnosis and treatment
First-line treatment:
After careful consideration of the risks and benefits of concurrent chemoradiotherapy, the patient declined radiotherapy.
What treatment options would you choose?
answer
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After informed consent in February 2017, the patient was given pemetrexed in combination with cisplatin (PP) as first-line chemotherapy.
After 4 cycles of combination chemotherapy, a partial response (PR) was obtained. Discuss with a radiation oncologist to determine whether chest radiation therapy should be started immediately. Due to poor lung function and increased tumor burden, we considered two additional chemotherapy regimens. Unfortunately, after the fifth cycle of chemotherapy, radiological evaluation showed PD.
Second-line therapy:
PP is not effective, what treatment plan will you choose?
answer
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Beginning in June 2017, the regimen was changed to gemcitabine plus cisplatin (GP) as a second-line chemotherapy.
However, after 1 cycle, the patient developed hemoptysis, and the imaging showed PD (Fig. 1A).
(Figure 1A: Imaging data showing PD)
With PP, GP drug connection failure, what should be the next treatment?
When a patient achieves CR, how should consolidation therapy be chosen? What kind of plan is it, the patient can actually achieve a survival time of nearly 5 years.
If you want to see more treatment progress, scan the QR code below / click to read the original article to view the treatment plan, and there is a treatment summary map~
参考文献：[1]. Borgelt B,Gelber R,Kramer S,Brady LW,Chang CH,Davis LW,Perez CA,Hendrickson FR. The palliation of brain metastases:final results of the first two studies by the Radiation Therapy Oncology Group.Int J Radiat Oncol Biol Phys.1980 Jan; 6(1):1-9.doi:10.1016/0360-3016(80)90195-9.PMID:6154024.https://pubmed.ncbi.nlm.nih.gov/6154024/[2]. Zhu X,Dong S,Tang J,Xie R,Wu H,Hofman P,Mrugala MM,Hu S.Lung cancer with brain metastases remaining in continuous complete remission due to pembrolizumab and temozolomide:a case report. Ann Transl Med.2022 Sep; 10(17):942.doi:10.21037/atm-22-4208. PMID:36172106; PMCID:PMC9511178.https://pubmed.ncbi.nlm.nih.gov/36172106/[3]. Goldberg SB,Schalper KA,Gettinger SN,Mahajan A,Herbst RS,Chiang AC,Lilenbaum R,Wilson FH,Omay SB,Yu JB,Jilaveanu L,Tran T,Pavlik K,Rowen E,Gerrish H,Komlo A,Gupta R,Wyatt H,Ribeiro M,Kluger Y,Zhou G,Wei W,Chiang VL,Kluger HM. Pembrolizumab for management of patients with NSCLC and brain metastases:long-term results and biomarker analysis from a non-randomised,open-label,phase 2 trial. Lancet Oncol.2020 May; 21(5):655-663.doi:10.1016/S1470-2045(20)30111-X.Epub 2020 Apr 3.PMID:32251621; PMCID:PMC7380514.https://pubmed.ncbi.nlm.nih.gov/32251621/[4]. Reck M,Rodríguez-Abreu D,Robinson AG,Hui R,Csőszi T,Fülöp A,Gottfried M,Peled N,Tafreshi A,Cuffe S,O'Brien M,Rao S,Hotta K,Leal TA,Riess JW,Jensen E,Zhao B,Pietanza MC,Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score≥50.J Clin Oncol.2021 Jul 20; 39(21):2339-2349.doi:10.1200/JCO.21.00174.Epub 2021 Apr 19.PMID:33872070; PMCID:PMC8280089.https://pubmed.ncbi.nlm.nih.gov/33872070/[5]. Zhu Y,Fu L,Jing W,Guo D,Kong L,Yu J.Effectiveness of temozolomide combined with whole brain radiotherapy for non-small cell lung cancer brain metastases. Thorac Cancer.2018 Sep; 9(9):1121-1128.doi:10.1111/1759-7714.12795.Epub 2018 Jun 27.PMID:29947170; PMCID:PMC6119610.https://pubmed.ncbi.nlm.nih.gov/29947170/[6]. Goldberg SB,Schalper KA,Gettinger SN,Mahajan A,Herbst RS,Chiang AC,Lilenbaum R,Wilson FH,Omay SB,Yu JB,Jilaveanu L,Tran T,Pavlik K,Rowen E,Gerrish H,Komlo A,Gupta R,Wyatt H,Ribeiro M,Kluger Y,Zhou G,Wei W,Chiang VL,Kluger HM. Pembrolizumab for management of patients with NSCLC and brain metastases:long-term results and biomarker analysis from a non-randomised,open-label,phase 2 trial. Lancet Oncol.2020 May; 21(5):655-663.doi:10.1016/S1470-2045(20)30111-X.Epub 2020 Apr 3.PMID:32251621; PMCID:PMC7380514.https://pubmed.ncbi.nlm.nih.gov/32251621/[7]. Germano G,Lamba S,Rospo G,Barault L,MagrìA,Maione F,Russo M,Crisafulli G,Bartolini A,Lerda G,Siravegna G,Mussolin B,Frapolli R,Montone M,Morano F,de Braud F,Amirouchene-Angelozzi N,Marsoni S,D'Incalci M,Orlandi A,Giraudo E,Sartore-Bianchi A,Siena S,Pietrantonio F,Di Nicolantonio F,Bardelli A.Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth. Nature.2017 Dec 7; 552(7683):116-120.doi:10.1038/nature24673. Epub 2017 Nov 29.PMID:29186113.https://pubmed.ncbi.nlm.nih.gov/29186113/
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