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A rationale for surgical debulking to improve anti-PD1 therapy outcome in non small cell lung cancer.

ABSTRACT: Anti-PD1 immunotherapy has emerged as a gold-standard treatment for first- or second-line treatment of stage IV NSCLC, with response rates ranging from 10 to 60%. Strategies to improve the disease control rate are needed. Several reports suggested that debulking surgery enhances anti-tumor immunity. We aimed at examining tumor burden as a predictive factor of anti-PD1 tretment efficacy and to evaluate the role of cytoreductive surgery in anti-PD1 treated NSCLC. Immunocompetent DBA/2 mice engrafted with various amount of allogeneic lung squamous cancer KLN-205 cells were treated with anti-PD1 monoclonal antibody. Mice engrafted with two tumors also underwent a debulking surgery or a sham procedure. Tumor volume was monitored to assess treatment efficacy. Tumor infiltrating lymphocytes were assessed by flow cytometry. In a retrospective study of 48 stage IV NSCLC patients treated with Nivolumab who underwent a 18-FDG PETscan before treatment onset, the prognostic role of metabolic tumor volume was analysed. Anti-PD1 treatment effect was greater in mice bearing smaller tumors. Treatment with higher doses of anti-PD1 antibody did not improve the outcome, independently of the size of the tumor. In mice bearing 2 tumors, excision of 1 tumor improved the anti-PD1 treatment effect on the remaining tumor. In 48 NSCLC patients receiving anti-PD1 treatment, high metabolic tumor volume was associated with poor overall survival and the absence of clinical benefit. Treg infiltration, but not effector T cells, was positively correlated to tumor volume. Taken together, our results suggest that tumor volume is a predictive factor of anti-PD1 efficacy in NSCLC. Additionally, an experimental murine model suggests that tumor debulking may improve control of residual tumor.

SUBMITTER: Guisier F

PROVIDER: S-EPMC6858444 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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A rationale for surgical debulking to improve anti-PD1 therapy outcome in non small cell lung cancer.

Guisier Florian F Cousse Stephanie S Jeanvoine Mathilde M Thiberville Luc L Salaun Mathieu M

Scientific reports 20191115 1

Anti-PD1 immunotherapy has emerged as a gold-standard treatment for first- or second-line treatment of stage IV NSCLC, with response rates ranging from 10 to 60%. Strategies to improve the disease control rate are needed. Several reports suggested that debulking surgery enhances anti-tumor immunity. We aimed at examining tumor burden as a predictive factor of anti-PD1 tretment efficacy and to evaluate the role of cytoreductive surgery in anti-PD1 treated NSCLC. Immunocompetent DBA/2 mice engraft ...[more]

PMID: 31729430

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Project description:BackgroundDue to the increasing number of trials with immune checkpoint inhibitors (ICIs) in the first-line therapy of non-small cell lung cancer (NSCLC) patients, we performed a systematic review and meta-analyses to investigate the difference between anti PD-1 and PD-L1 antibodies, used alone or in combination with chemotherapy, through adjusted indirect analysis to minimize the potential bias regarding overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3-5 adverse events (AEs).MethodsA systematic review of studies reporting clinical outcomes and toxicity associated with first-line therapy employing anti-PD1 or anti-PD-L1 antibodies alone, or in combination with chemotherapy, to treat metastatic, treatment-naïve NSCLC patients was performed. Primary outcomes were OS, PFS, ORR and grade 3-5 AEs. We used a random-effects model to generate pooled estimates for proportions. Meta-analyses using pooled risk ratios were performed for binary outcomes from comparative studies with the random effects model.ResultsA total of 13 eligible studies met our eligibility criteria, including 7673 patients. In the ICI-chemotherapy combination subgroup, we observed that anti-PD1 therapy was associated with better OS (p = 0.022) and PFS (p = 0.029) compared with anti-PD-L1 therapy. In the monotherapy subgroup, there was no statistical difference between the use of anti-PD-1 and anti-PD-L1 for OS and PFS. With regard to ORR and toxicity, in the ICI-chemotherapy combination subgroup, we observed a trend of better ORR (p = 0.12) with the use of anti-PD1 therapy and less frequent grade 3-5 AEs compared to the use of anti-PD-L1 therapy (p = 0.0302). In the monotherapy subgroup, there was no statistical difference between the use of anti-PD-1 and anti-PD-L1 regarding ORR and toxicity.ConclusionsOur study suggests that PD-1 drug plus chemotherapy is superior to anti-PD-L1 plus chemotherapy for NSCLC; nevertheless, as monotherapy, both strategies appear to be similar.

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A rationale for surgical debulking to improve anti-PD1 therapy outcome in non small cell lung cancer.

Publications

A rationale for surgical debulking to improve anti-PD1 therapy outcome in non small cell lung cancer.

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