Management of small cell lung cancer (SCLC) has not changed over the last decades. In more recent years, alterations of DNA repair machinery and other molecular pathways have been identified in SCLC ...and preclinical data suggest that dysregulation of these pathways might offer new therapeutic opportunities.While immune checkpoint inhibitors (ICIs) have had a major impact on the clinical outcome of several solid tumors, including non-small cell lung cancer, the potential role of ICIs is currently under investigation in SCLC and some promising data are available. However, several clinical and biological hurdles have to be overcome and predictive markers are still eagerly needed. Knowledge of molecular pathways specifically involved in SCLC growth and treatment resistance is essential for a more rational planning of new combinations including ICIs.The present manuscript summarizes the current clinical evidence on immunotherapy in SCLC, describes the molecular bases underlying treatment resistance and discusses the potentialities and the rationale of different therapeutic combinations.
The prognosis of small-cell lung cancer (SCLC) is dismal and new effective therapies are needed. Immunotherapy looks promising, but no molecular predictive markers are currently available, and data ...on immune microenvironment are very limited.
We retrospectively analysed 104 SCLC cases. Immunohistochemistry evaluation of PD-L1 was performed both on tumour cells (TCs) and on tumour-infiltrating immune cells (TIICs) by using anti-PD-L1 22C3 antibody (DAKO) and categorised by using 1% as cut-off point. Tumour-infiltrating lymphocytes (TILs) were characterised by using anti-CD8 and anti-FOXP3 antibodies. Semi-quantitative score was used and categorised as positive versus negative/low. The relation of molecular markers with prognosis and with clinical variables was evaluated.
The analysis included 66 stage I–III patients (48 surgically resected, 18 treated with radical-intent chemoradiotherapy) and 38 metastatic cases. In the overall study population, PD-L1 was expressed on TCs and TIICs in 25% and 40% of cases, respectively. The proportion of PD-L1-positive cases was significantly higher in stage I–III versus metastatic patients (32% versus 13%, p: 0.034 for TCs; 51.5% versus 21% for TIICs, p: 0.002). CD8- and FOXP3-positive TILs were present in 59% and 72% of samples, respectively. The presence of FOXP3-TILs was associated with improved prognosis among non-metastatic patients, with a hazard ratio for survival of 0.32 (95% confidence interval CI: 0.16–0.7, p: 0.006) for univariate analysis, and 0.37 (95% CI: 0.17–0.81, p: 0.013) for multivariate analysis.
Immune contexture of SCLC may differ according to stage. The presence of FOXP3-positive TILs is a potential prognostic marker for stage I–III SCLCs and warrants further investigation.
•The study depicts distribution of PD-L1 expression in small-cell lung cancer (SCLC) according to stage.•The study characterises tumour-infiltrating lymphocytes (TILs) in SCLC.•Independent positive prognostic impact of FOXP3-TILs is shown in stage I–III SCLCs.
Immunotherapy represents the standard of care in the first-line treatment of advanced non-small-cell lung cancer (NSCLC), either as monotherapy in high programmed death-ligand 1 (PD-L1)-positive ...tumors (≥50%) or in combination with platinum-based chemotherapy regardless of PD-L1 status. However, most pivotal clinical trials of immune checkpoint inhibitors (ICIs) did not include patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2. Hence, a consensus is lacking on the safety and efficacy of ICIs in this specific subgroup of patients.
A virtual International Expert Panel took place in July 2021 with the aim of reviewing the available evidence on the use of ICIs in NSCLC patients with ECOG PS 2, both in clinical practice and in a research setting.
All panelists expressed concern about the applicability of currently available PS scales to evaluate patients for ICI treatment. The panelists agreed that, though limited, the available data support the safety of single-agent immunotherapy in PS 2 NSCLC patients, whereas concern was raised on the safety of ICI combinations, mainly related to chemotherapy and/or anti-cytotoxic T-lymphocyte-associated antigen 4 toxicity. On the basis of reviewed data, ICI efficacy may be speculated in PS 2 NSCLC patients; however, PS 2 remains a negative prognostic category as compared to PS 0-1 in patients treated with ICI, as it is for chemotherapy. The panelists defined high, medium and low priorities in clinical research. High priority was attributed to the inclusion of PS 2 patients in prospective clinical trials and the specific evaluation of combined ICI treatments with attenuated chemotherapy doses.
Based on the current evidence, the panelists outlined the major limitations affecting PS 2 patients with NSCLC and reached common considerations on the feasibility, safety and effectiveness of ICI monotherapy and ICI combinations in the first-line setting.
•A consensus on the use of ICIs in lung cancer patients with PS 2 is lacking.•An International Expert Panel Meeting was held in 2021 to review and discuss available evidence on this topic.•Overall, agreement was reached on the safety of ICI monotherapy in PS 2 patients, with concerns for chemo–ICI combinations.•Common considerations were reached on the priorities for clinical research to investigate PS 2 lung cancer population.
The use of immune checkpoint inhibitors (ICIs) in the front-line treatment of advanced non-small-cell lung cancer (NSCLC) is currently the standard of care. However, as clinical trials include a very ...limited number of elderly patients, evidence on the safety and efficacy of using ICI-based regimens is still limited.
A virtual International Expert Panel took place in July 2022 to review the available evidence on the use of ICI-based regimens in the first-line setting in elderly patients with NSCLC and provide a position paper on the field both in clinical practice and in a research setting.
All panelists agreed that age per se is not a limitation for ICI treatments, as the elderly should be considered only as a surrogate for other clinical factors of frailty. Overall, ICI efficacy in the elderly population is supported by reviewed data. In addition, the panelists were confident that available data support the safety of single-agent immunotherapy in elderly patients with NSCLC. Conversely, concerns were expressed on the safety of chemo + ICI-based combination, which were considered mainly related to the toxicities of chemotherapy components. Therefore, suggestions were proposed to tailor combined approaches in the elderly patients with NSCLC. The panelists defined high, medium, and low priorities in clinical research. High priority was attributed to implementing the real-world assessment of elderly patients treated with ICIs, who are mostly underrepresented in pivotal clinical trials.
Based on the current evidence, the panelists outlined the significant limitations affecting the clinical practice in elderly patients affected by NSCLC, and reached common considerations on the feasibility, safety, and effectiveness of ICI monotherapy and ICI combinations in the first-line setting.
•Elderly patients are not well represented in clinical trials evaluating ICIs in lung cancer.•An Expert Panel Meeting was held to provide a position paper on the use of ICIs in the elderly population.•Common considerations on feasibility, safety, and effectiveness of different ICI treatments were pointed out.
•Pivotal trials of COVID-19 vaccines did not include cancer patients, with questions remaining about their safety and efficacy in this population•In this cohort study we investigated the safety and ...efficacy of COVID-19 vaccines in 207 patients with thoracic cancer receiving anticancer treatments•After long follow-up, there were no safety signals of concern and only 0.5% of patients experienced grade 3 vaccine-related adverse events•In our cohort ∼10% of patients had a positive nasal swab after vaccination: 67% asymptomatic and 33% symptomatic (symptoms were mild)
Pivotal trials of COVID-19 vaccines did not include cancer patients with questions remaining in this population. Particularly in patients with thoracic malignancies receiving anticancer treatments, the safety of these vaccines has so far been little investigated.
This is a prospective trial of patients with thoracic cancer receiving anticancer treatments and COVID-19 vaccines at the Division of Thoracic Oncology of European Institute of Oncology between February and September 2021.
A total 207 patients affected by thoracic cancers (199 lung cancers and 8 mesotheliomas) had received Covid-19 vaccines (206 mRNA vaccines and 1 virus-vectored vaccine). The majority of patients had at least one comorbidity (76.3%). They were concomitantly treating with targeted therapy (TT) (45.9%), immunotherapy (IO) (22.7%), and chemotherapy (CT) (14%). A total of 64 AEs (15.6%) were observed after administration of Sars-Cov-2 vaccine. The majority of AEs were grade 1 G1 (6.3%) and G2 (8.8%), only two events were G3 (0.5%). The median follow-up was 9 months (range 1-22 months), during this follow-up 21 patients (10.1%) had a positive nasal swab, most of the patients were asymptomatic (67%) and the symptomatic ones (33%) had mild symptoms and fewer complications and hospitalizations.
COVID-19 m-RNA vaccines appear to be safe in the cohort of patients with thoracic malignances in active treatment, including those receiving immunotherapy. Considering the high morbidity and mortality associated with COVID-19 in patients with lung cancer receiving active treatments, our study supports the current vaccine prioritization, third and/or fourth dose, of all cancer patients with active treatment.
This is a prospective trial of 207 patients with thoracic cancer receiving anticancer treatments and COVID-19 vaccines. After long follow-up, there were no safety signals of concern and only 0.5% of patients experienced grade 3 vaccine-related adverse events. Our study supports the current vaccine prioritization, third and/or fourth dose of all lung cancer patients with active treatment.
PDF
