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. 2024 Mar 12;3(3):CD013377.
doi: 10.1002/14651858.CD013377.pub2.

Therapeutic vaccines for advanced non-small cell lung cancer

Marcela Cortés-Jofré  1 , Mikel Rueda-Etxebarria  2 , Emeline Orillard  3 , Elena Jimenez Tejero  4   5 , José-Ramón Rueda  6
Affiliations

Therapeutic vaccines for advanced non-small cell lung cancer

Marcela Cortés-Jofré et al. Cochrane Database Syst Rev. .

Abstract

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.

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Conflict of interest statement

Marcela Cortés‐Jofré: none known.

Mikel Rueda‐Etxebarria: none known.

Emeline Orillard: none known.

Elena Jimenez Tejero: none known.

José‐Ramón Rueda: none known.

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1: TG4010 added to chemotherapy versus chemotherapy alone in first line treatment, Outcome 1: Overall survival
1.2
1.2. Analysis
Comparison 1: TG4010 added to chemotherapy versus chemotherapy alone in first line treatment, Outcome 2: Progression‐free survival
1.3
1.3. Analysis
Comparison 1: TG4010 added to chemotherapy versus chemotherapy alone in first line treatment, Outcome 3: Adverse events grades 3 to 5 (Participants with at least one serious adverse event)
1.4
1.4. Analysis
Comparison 1: TG4010 added to chemotherapy versus chemotherapy alone in first line treatment, Outcome 4: Survival rates at 3 years
2.1
2.1. Analysis
Comparison 2: Epidermal growth factor vaccines versus best supportive care for switch maintenance after first‐line treatment, Outcome 1: Overall survival
2.2
2.2. Analysis
Comparison 2: Epidermal growth factor vaccines versus best supportive care for switch maintenance after first‐line treatment, Outcome 2: Adverse events grades 3 to 5 (Participants with at least one serious adverse event)
2.3
2.3. Analysis
Comparison 2: Epidermal growth factor vaccines versus best supportive care for switch maintenance after first‐line treatment, Outcome 3: Survival rates at 3 years
2.4
2.4. Analysis
Comparison 2: Epidermal growth factor vaccines versus best supportive care for switch maintenance after first‐line treatment, Outcome 4: Survival rates at 5 years
2.5
2.5. Analysis
Comparison 2: Epidermal growth factor vaccines versus best supportive care for switch maintenance after first‐line treatment, Outcome 5: Health‐related quality of life
3.1
3.1. Analysis
Comparison 3: hTERT (vx‐001) vaccine versus placebo as post‐chemotherapy maintenance treatment, Outcome 1: Overall survival
3.2
3.2. Analysis
Comparison 3: hTERT (vx‐001) vaccine versus placebo as post‐chemotherapy maintenance treatment, Outcome 2: Survival rates at 40 months
3.3
3.3. Analysis
Comparison 3: hTERT (vx‐001) vaccine versus placebo as post‐chemotherapy maintenance treatment, Outcome 3: Survival rates at 5 years
4.1
4.1. Analysis
Comparison 4: Racotumomab‐alum vaccine versus placebo for switch maintenance after first‐line treatment, Outcome 1: Overall survival
4.2
4.2. Analysis
Comparison 4: Racotumomab‐alum vaccine versus placebo for switch maintenance after first‐line treatment, Outcome 2: Progression‐free survival
4.3
4.3. Analysis
Comparison 4: Racotumomab‐alum vaccine versus placebo for switch maintenance after first‐line treatment, Outcome 3: Adverse events grade 3‐5 (Participants with at least one serious adverse event)
4.4
4.4. Analysis
Comparison 4: Racotumomab‐alum vaccine versus placebo for switch maintenance after first‐line treatment, Outcome 4: Survival rates at 3 years
4.5
4.5. Analysis
Comparison 4: Racotumomab‐alum vaccine versus placebo for switch maintenance after first‐line treatment, Outcome 5: Survival rates at 5 years
5.1
5.1. Analysis
Comparison 5: Racotumomab‐alum vaccine versus docetaxel for switch maintenance treatment after first‐line treatment, Outcome 1: Adverse events grades 3 to 5 (Participants with at least one serious adverse event)
6.1
6.1. Analysis
Comparison 6: Personalised peptide vaccine versus docetaxel plus placebo after first‐line treatment, Outcome 1: Overall survival
6.2
6.2. Analysis
Comparison 6: Personalised peptide vaccine versus docetaxel plus placebo after first‐line treatment, Outcome 2: Progression‐free survival
7.1
7.1. Analysis
Comparison 7: OSE2101 vaccine versus chemotherapy alone in HLA‐A2+ advanced NSCLC in second/third‐line treatment after failure with immune checkpoint inhibitors, Outcome 1: Overall survival
7.2
7.2. Analysis
Comparison 7: OSE2101 vaccine versus chemotherapy alone in HLA‐A2+ advanced NSCLC in second/third‐line treatment after failure with immune checkpoint inhibitors, Outcome 2: Adverse events grades 3 to 5 (Participants with at least one serious adverse event)
8.1
8.1. Analysis
Comparison 8: SRL172 (killed Mycobacterium vaccae) added to chemotherapy versus chemotherapy alone in first‐line or maintenance treatment, Outcome 1: Adverse events grade 3‐5 (Participants with at least one serious adverse event)
8.2
8.2. Analysis
Comparison 8: SRL172 (killed Mycobacterium vaccae) added to chemotherapy versus chemotherapy alone in first‐line or maintenance treatment, Outcome 2: Quality of life: mean change from baseline in Global Health Status score
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