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Background: Lung cancer is a cancer of the elderly, with a median age at diagnosis of 71. More than one-third of people diagnosed with lung cancer are over 75 years old. Immune checkpoint inhibitors (ICIs) are special antibodies that target a pathway in the immune system called the programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway. These antibodies help the immune system fight cancer cells by blocking signals that cancer cells use to avoid being attacked by the immune system. ICIs have changed the treatment of people with lung cancer. In particular, for people with previously-untreated advanced non-small cell lung cancer (NSCLC), current first-line treatment now comprises ICIs plus platinum-based chemotherapy, rather than platinum-based chemotherapy alone, regardless of their PD-L1 expression status. However, as people age, their immune system changes, becoming less effective in its T cell responses. This raises questions about how well ICIs work in older adults., Objectives: To assess the effects of immune checkpoint inhibitors (ICIs) in combination with platinum-based chemotherapy compared to platinum-based chemotherapy (with or without bevacizumab) in treatment-naïve adults aged 65 years and older with advanced NSCLC., Search Methods: We searched the Cochrane Lung Cancer Group Trial Register, CENTRAL, MEDLINE, Embase, two other trial registers, and the websites of drug regulators. The latest search date was 23 August 2023. We also checked references and searched abstracts from the meetings of seven cancer organisations from 2019 to August 2023., Selection Criteria: We included randomised controlled trials (RCTs) that reported on the efficacy and safety of adding ICIs to platinum-based chemotherapy compared to platinum-based chemotherapy alone for people 65 years and older who had not previously been treated. All data emanated from international multicentre studies involving adults with histologically-confirmed advanced NSCLC who had not received any previous systemic anticancer therapy for their advanced disease., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival and treatment-related adverse events (grade 3 or higher). Our secondary outcomes were progression-free survival, objective response rate, time to response, duration of response, and health-related quality of life (HRQoL)., Main Results: We included 17 primary studies, with a total of 4276 participants, in the review synthesis. We identified nine ongoing studies, and listed one study as 'awaiting classification'. Twelve of the 17 studies included people older than 75 years, accounting for 9% to 13% of their participants. We rated some studies as having 'some concerns' for risk of bias arising from the randomisation process, deviations from the intended interventions, or measurement of the outcome. The overall GRADE rating for the certainty of the evidence ranged from moderate to low because of the risk of bias, imprecision, or inconsistency. People aged 65 years and older The addition of ICIs to platinum-based chemotherapy probably increased overall survival compared to platinum-based chemotherapy alone (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.70 to 0.88; 8 studies, 2093 participants; moderate-certainty evidence). Only one study reported data for treatment-related adverse events (grade 3 or higher). The frequency of treatment-related adverse events may not differ between the two treatment groups (risk ratio (RR) 1.09, 95% CI 0.89 to 1.32; 1 study, 127 participants; low-certainty evidence). The addition of ICIs to platinum-based chemotherapy probably improves progression-free survival (HR 0.61, 95% CI 0.54 to 0.68; 7 studies, 1885 participants; moderate-certainty evidence). People aged 65 to 75 years, inclusive The addition of ICIs to platinum-based chemotherapy probably improved overall survival compared to platinum-based chemotherapy alone (HR 0.75, 95% CI 0.65 to 0.87; 6 studies, 1406 participants; moderate-certainty evidence). Only one study reported data for treatment-related adverse events (grade 3 or higher). The frequency of treatment-related adverse events probably increased in people treated with ICIs plus platinum-based chemotherapy compared to those treated with platinum-based chemotherapy alone (RR 1.47, 95% CI 1.02 to 2.13; 1 study, 97 participants; moderate-certainty evidence). The addition of ICIs to platinum-based chemotherapy probably improved progression-free survival (HR 0.64, 95% CI 0.57 to 0.73; 8 studies, 1466 participants; moderate-certainty evidence). People aged 75 years and older There may be no difference in overall survival in people treated with ICIs combined with platinum-based chemotherapy compared to platinum-based chemotherapy alone (HR 0.90, 95% CI 0.70 to 1.16; 4 studies, 297 participants; low-certainty evidence). No data on treatment-related adverse events were available in this age group. The effect of combination ICI and platinum-based chemotherapy on progression-free survival is uncertain (HR 0.83, 95% CI 0.51 to 1.36; 3 studies, 226 participants; very low-certainty evidence). Only three studies assessed the objective response rate. For time to response, duration of response, and health-related quality of life, we do not have any evidence yet., Authors' Conclusions: Compared to platinum-based chemotherapy alone, adding ICIs to platinum-based chemotherapy probably leads to higher overall survival and progression-free survival, without an increase in treatment-related adverse events (grade 3 or higher), in people 65 years and older with advanced NSCLC. These data are based on results from studies dominated by participants between 65 and 75 years old. However, the analysis also suggests that the improvements reported in overall survival and progression-free survival may not be seen in people older than 75 years., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness and safety of immune checkpoint inhibitors (ICI) as monotherapy or in combination compared to standard of care for elderly people (≥ 65 years) with non-small cell lung cancer (NSCLC)., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: New strategies in immunotherapy with specific antigens that trigger an anti-tumour immune response in people with lung cancer open the possibility of developing therapeutic vaccines aimed at boosting the adaptive immune response against cancer cells., Objectives: To evaluate the effectiveness and safety of different types of therapeutic vaccines for people with advanced non-small cell lung cancer., Search Methods: We searched CENTRAL, MEDLINE, Embase, Wanfang Data, and China Journal Net (CNKI) up to 22 August 2023., Selection Criteria: We included parallel-group, randomised controlled trials evaluating a therapeutic cancer vaccine, alone or in combination with other treatments, in adults (> 18 years) with advanced non-small cell lung cancer (NSCLC), whatever the line of treatment., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival, progression-free survival, and serious adverse events; secondary outcomes were three- and five-year survival rates and health-related quality of life., Main Results: We included 10 studies with 2177 participants. The outcome analyses included only 2045 participants (1401 men and 644 women). The certainty of the evidence varied by vaccine and outcome, and ranged from moderate to very low. We report only the results for primary outcomes here. TG4010 The addition of the vector-based vaccine, TG4010, to chemotherapy, compared with chemotherapy alone in first-line treatment, may result in little to no difference in overall survival (hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.65 to 1.05; 2 studies, 370 participants; low-certainty evidence). It may increase progression-free survival slightly (HR 0.74, 95% CI 0.55 to 0.99; 1 study, 222 participants; low-certainty evidence). It may result in little to no difference in the proportion of participants with at least one serious treatment-related adverse event, but the evidence is very uncertain (risk ratio (RR) 0.70, 95% CI 0.23 to 2.19; 2 studies, 362 participants; very low-certainty evidence). Epidermal growth factor vaccine Epidermal growth factor vaccine, compared to best supportive care as switch maintenance treatment after first-line chemotherapy, may result in little to no difference in overall survival (HR 0.82, 95% CI 0.66 to 1.02; 1 study, 378 participants; low-certainty evidence), and in the proportion of participants with at least one serious treatment-related adverse event (RR 1.32, 95% CI 0.88 to 1.98; 2 studies, 458 participants; low-certainty evidence). hTERT (vx-001) The hTERT (vx-001) vaccine compared to placebo as maintenance treatment after first-line chemotherapy may result in little to no difference in overall survival (HR 0.97, 95% CI 0.70 to 1.34; 1 study, 190 participants). Racotumomab Racotumomab compared to placebo as a switch maintenance treatment post-chemotherapy was assessed in one study with 176 participants. It may increase overall survival (HR 0.63, 95% CI 0.46 to 0.87). It may make little to no difference in progression-free survival (HR 0.73, 95% CI 0.53 to 1.00) and in the proportion of people with at least one serious treatment-related adverse event (RR 1.03, 95% CI 0.15 to 7.18). Racotumomab versus docetaxel as switch maintenance therapy post-chemotherapy was assessed in one study with 145 participants. The study did not report hazard rates on overall survival or progression-free survival time, but the difference in median survival times was very small - less than one month. Racotumomab may result in little to no difference in the proportion of people with at least one serious treatment-related adverse event compared with docetaxel (RR 0.89, 95% CI 0.44 to 1.83). Personalised peptide vaccine Personalised peptide vaccine plus docetaxel compared to docetaxel plus placebo post-chemotherapy treatment may result in little to no difference in overall survival (HR 0.80, 95% CI 0.42 to 1.52) and progression-free survival (HR 0.78, 95% CI 0.43 to 1.42). OSE2101 The OSE2101 vaccine compared with chemotherapy, after chemotherapy or immunotherapy, was assessed in one study with 219 participants. It may result in little to no difference in overall survival (HR 0.86, 95% CI 0.62 to 1.19). It may result in a small difference in the proportion of people with at least one serious treatment-related adverse event (RR 0.95, 95% CI 0.91 to 0.99). SRL172 The SRL172 vaccine of killed Mycobacterium vaccae, added to chemotherapy, compared to chemotherapy alone, may result in no difference in overall survival, and may increase the proportion of people with at least one serious treatment-related adverse event (RR 2.07, 95% CI 1.76 to 2.43; 351 participants)., Authors' Conclusions: Adding a vaccine resulted in no differences in overall survival, except for racotumomab, which showed some improvement compared to placebo, but the difference in median survival time was very small (1.4 months) and the study only included 176 participants. Regarding progression-free survival, we observed no differences between the compared treatments, except for TG4010, which may increase progression-free survival slightly. There were no differences between the compared treatments in serious treatment-related adverse events, except for SRL172 (killed Mycobacterium vaccae) added to chemotherapy, which was associated with an increase in the proportion of participants with at least one serious treatment-related adverse event, and OSE2101, which may decrease slightly the proportion of people having at least one serious treatment-related adverse event. These conclusions should be interpreted cautiously, as the very low- to moderate-certainty evidence prevents drawing solid conclusions: many vaccines were evaluated in a single study with small numbers of participants and events., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: Universal cancer peptide-based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD4+ T helper-1 response directed against telomerase. This phase Ib/IIa trial was designed to test the safety, immunogenicity, and efficacy of a three-dose schedule in patients with metastatic non-small-cell lung cancer (NSCLC)., Patients and Methods: Patients with refractory NSCLC were assigned to receive three vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg) using a Bayesian-based phase Ib followed by phase IIa de-escalating design. The primary end points were dose-limiting toxicity and immune response after three first doses of vaccine. Secondary end points were overall survival (OS) and progression-free survival at 1 year., Results: A total of 59 patients received UCPVax; 95% had three prior lines of systemic therapy. No dose-limiting toxicity was observed in 15 patients treated in phase Ib. The maximum tolerated dose was 1 mg. Fifty-one patients were eligible for phase IIa. The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between three dose levels. Twenty-one (39%) patients achieved disease control (stable disease, n = 20; complete response, n = 1). The 1-year OS was 34.1% (95% CI, 23.1 to 50.4), and the median OS was 9.7 months, with no significant difference between dose levels. The 1-year progression-free survival and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders ( P = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders ( P = .005), respectively., Conclusion: UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.