Combining immune checkpoint inhibitors with chemotherapy in advanced solid tumours: A review

• Published in: European journal of cancer (1990) 2021-11, Vol.158, p.47-62
• Main Authors: Larroquette, Mathieu, Domblides, Charlotte, Lefort, Félix, Lasserre, Matthieu, Quivy, Amandine, Sionneau, Baptiste, Bertolaso, Pauline, Gross-Goupil, Marine, Ravaud, Alain, Daste, Amaury
• Format: Article
• Language: English
• Subjects: Advanced solid tumours; Apoptosis; Bladder cancer; Cancer therapies; Cell death; Chemo-immunotherapy; Chemotherapy; Clinical efficacy; Clinical trials; Head & neck cancer; Immune checkpoint inhibitors; Immunogenicity; Immunological tolerance; Inhibitors; Lung cancer; Maintenance management; Microenvironments; Non-small cell lung carcinoma; PD-1 protein; PD-L1 protein; Pembrolizumab; Safety; Small cell lung carcinoma; Solid tumors; Survival; Synergistic effect; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2021.09.013

The use of immune checkpoint inhibitors (ICIs), especially anti-programmed cell death 1 (PD1) and anti-programmed cell death ligand 1 (PD-L1), has changed practices in oncology, becoming a new standard of care in first or subsequent lines for several cancer subtypes. Recent data have highlighted the ability of standard chemotherapy to enhance immunogenicity and/or to break immunoresistance of the tumour and its microenvironment, leading to a rationale for the use of ICIs in combination with the standard chemotherapy regimen to improve efficacy of cancer treatment. Here, we propose to review randomised clinical trials evaluating concomitant administration of ICIs and chemotherapy, to assess clinical efficacy and safety profiles in advanced solid tumours. Association of these two modes of action on treatments has shown improved overall survival and better objective response rates than standard chemotherapy, especially in first-line treatment of non-small cell lung cancer (NSCLC) and for PD1/PD-L1 enriched tumours, highlighting a potential synergistic effect of this treatment combination in certain tumour types. However, improved survival results with the use of anti-PD-L1 avelumab as a maintenance schedule for bladder cancer raises the question of the most appropriate approach between sequential and concomitant administration of chemoimmunotherapy. To date, no trials have compared in a head-to-head protocol the administration of concomitant chemoimmunotherapy with chemotherapy, used for tumour debulking, followed by administration of ICIs. Regarding the tolerance profile, no new safety signals were found with the combination tested to date. Interestingly, recent results have shown an improved Progression Free survival 2 (PFS2) (defined as the progression after the next line of therapy) in head-and-neck cancers or NSCLC after a first-line pembrolizumab-chemotherapy combination, suggesting a potential long-lasting effect of ICIs when used in combination in the first-line setting. •Monotherapy of immune checkpoint inhibitors (ICIs) has changed the treatment of cancer with often low progression-free survival.•Combination of ICI with chemotherapy increased the median PFS (mPFS) comparing ICI alone.•Efficacy of this combination differs according to the type of chemotherapy and tumour.