Vaccine boosts advanced NSCLC patient survival

By Lynda Williams, Senior medwireNews Reporter

Investigation of a vaccine targeting a glycoside present in non-small-cell lung cancer (NSCLC) has demonstrated efficacy as a switch therapy for patients with stable, advanced disease after chemotherapy.

Racotumomab-alum is an anti-idiotype vaccine against the neu glycolyl (NeuGc)-containing ganglioside NeuGcGM3 and has been shown in phase I trials to induce a high immunoglobulin (Ig)M and IgG antibody response against this glycolipid, explain Amparo Macias, from the Center of Molecular Immunolgy in Havana, Cuba, and co-workers.

To investigate further, the team randomly assigned stage IIIb or IV NSCLC patients who had achieved at least a stable response with chemotherapy to receive racotumomab-alum (five immunisations over 2 weeks followed by re-immunisation every 4 weeks) or placebo. Treatment continued past disease progression, until the patient had severe worsening of their performance status or experienced toxicity.

The 87 patients given racotumomab-alum had a median overall survival of 8.23 months compared with just 6.80 months for the 89 patients who received placebo, a significant difference with a hazard ratio (HR) of 0.63.

Progression-free survival was also significantly better in the vaccinated patients than controls, at a median of 5.33 versus 3.90 months and a HR of 0.73.

The team reports in Clinical Cancer Research that all patients given racotumomab-alum developed IgM antibodies against NeuGcGM3 and 95.8% of patients had a strong IgM and IgG response to the NeuGcGM3 ganglioside.

Hyperimmune sera from 11 of 24 tested patients contained IgM and IgG antibodies and the remainder had IgM or IgG antibodies. All but two patients of these patients had hyperimmune sera able to bind to a cell line expressing NeuGcGM3 and hypersera from 18 of the patients had a cytotoxic effect.

Moreover, among patients who developed IgM anti-NeuGcGM3 antibodies, there were correlations between recognition of and cytotoxicity of the NeuGcGM3-expressing cell line and patient survival. Indeed, patients whose IgM antibodies were able to destroy at least 30% of exposed NeuGcGM3-expressing cells had significantly longer median survival than those who did not (19.63 vs 8.23 months).

“Although the mechanism of action of racotumomab seems to be associated with the induction of cytotoxic antibodies capable to kill NeuGcGM3-expressing cells, others mechanisms cannot be ruled out”, the researchers write.

They believe: “This study suggests the value of anti-idiotype immunization to generate vigorous serologic responses in situations where tumor-associated antigens are poorly immunogenic.”

Noting the need for further research into this mechanism, the team concludes that a multinational phase III trial for racotumomab is now ongoing in patients with advanced NSCLC, with an option to continue with chemotherapy for those who progress during the immunotherapy.

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