Back to Search
Start Over
Impact of chemoradiotherapy on the immune-related tumour microenvironment and efficacy of anti-PD-(L)1 therapy for recurrences after chemoradiotherapy in patients with unresectable locally advanced non-small cell lung cancer
- Source :
- European Journal of Cancer. 140:28-36
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Background A history of radiotherapy and chemoradiotherapy (CRT) reportedly increases the efficacy of the PD-1 blockade in patients with advanced non-small cell lung cancer (NSCLC). We investigated the efficacy of anti-PD-(L)1 therapy after CRT failure and how CRT changes the status of PD-L1 expression on tumours and on tumour-infiltrated lymphocytes (TILs). Methods We retrospectively reviewed patients with unresectable locally advanced NSCLC (LA-NSCLC) who were treated with CRT between 2007 and 2018 and evaluated the efficacy of the PD-(L)1 blockade after CRT failure. We also compared the PD-L1 (clone: 22C3) expression levels and the tumoral and stromal distributions of CD8-positive TILs using paired formalin-fixed, paraffin-embedded specimens obtained before and after CRT. Results We identified 422 patients and 65 patients who had relapsed after CRT received anti-PD-(L)1 therapy. The objective response rate (ORR) and the progression-free survival (PFS) after anti-PD-(L)1 therapy were 48% and 8.7 months (95% CI, 4.5–13), respectively. The RR and PFS did not differ according to the pre-CRT PD-L1 expression levels. PD-L1 expression changed in 16 of the 18 patients between before and after CRT, but a specific trend was not seen (increased, 9 patients; decreased, 7 patients; no change, 2 patients). In contrast, the density of tumoral CD8-positive TILs increased after CRT treatment (pre-CRT median, 110/mm2 versus post-CRT median, 470/mm2; p = 0.025). Conclusions Anti-PD-(L)1 therapy was effective in patients with LA-NSCLC who had progressed after CRT regardless of their pre-CRT PD-L1 expression. The efficacy of anti-PD-(L)1 therapy for patients with NSCLC with CRT failure was superior to that of standard second-line treatment for patients with advanced NSCLC.
- Subjects :
- Adult
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Lung Neoplasms
genetic structures
medicine.medical_treatment
Locally advanced
Antineoplastic Agents
CD8-Positive T-Lymphocytes
B7-H1 Antigen
03 medical and health sciences
Lymphocytes, Tumor-Infiltrating
0302 clinical medicine
Immune system
Carcinoma, Non-Small-Cell Lung
Internal medicine
Tumor Microenvironment
medicine
Humans
In patient
cardiovascular diseases
Lung cancer
Aged
Retrospective Studies
Aged, 80 and over
business.industry
Chemoradiotherapy
Middle Aged
equipment and supplies
medicine.disease
Progression-Free Survival
Blockade
Radiation therapy
030104 developmental biology
030220 oncology & carcinogenesis
cardiovascular system
Female
Neoplasm Recurrence, Local
business
CD8
circulatory and respiratory physiology
Subjects
Details
- ISSN :
- 09598049
- Volume :
- 140
- Database :
- OpenAIRE
- Journal :
- European Journal of Cancer
- Accession number :
- edsair.doi.dedup.....493ed2941150b6a0a3ba0437878fc285