Immunotherapy: is a minor god yet in the pantheon of treatments for lung cancer?

Abstract

Immunotherapy has been studied for many years in lung cancer without significant results, making the majority of oncologists quite skeptical about its possible application for non-small cell lung cancer treatment. However, the recent knowledge about immune escape and subsequent ‘cancer immunoediting’ has yielded the development of new strategies of cancer immunotherapy, heralding a new era of lung cancer treatment. Cancer vaccines, including both whole-cell and peptide vaccines have been tested both in early and advanced stages of non-small cell lung cancer. New immunomodulatory agents, including anti-CTLA4, anti-PD1/PDL1 monoclonal antibodies, have been investigated as monotherapy in metastatic lung cancer. To date, these treatments have shown impressive results of efficacy and tolerability in early clinical trials, leading to testing in several large, randomized Phase III trials. As these results will be confirmed, these drugs will be available in the near future, offering new exciting therapeutic options for lung cancer treatment.

Keywords::

• belagenpumatucel-L
• CIMAvax
• GVAX
• immunotherapy
• ipilimumab
• MAGE-A3
• non-small cell lung cancer
• PD-1
• PD-L1
• racotumomab
• tecemotide
• TG4010
• vaccines

Financial & competing interests disclosure

L Raez has received research support from GSK, Merck Serono, Roche and MSD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Survival outcomes of advanced non-small cell lung cancer (NSCLC) patients are still poor for the majority of them, but the introduction of targeted therapies represented a critical turning point for the treatment of molecular selected patients.

• The immune system is widely involved in the complex mechanisms of development, growth and spreading of malignant tumors, including NSCLC.

• Although lung cancer has been considered non-immunogenic for years, some scientific evidences suggest the opposite, especially for squamous NSCLC.

• Two different strategies of generating an immune response against cancer: enhancing immune stimulating components to start or maintain an effective response or inhibiting suppressing factors limiting the immune response.

• Many vaccines have been evaluated using different targets and others are still under evaluation. Promising data are coming especially from belagenpumatucel-L, a whole-cell vaccine, melanoma-associated antigen-A3 vaccines and tecemotide, an anti-MUC1 vaccine.

• The inhibition of immune checkpoints is a possible strategy to enhance immune response against cancer.

• Ipilimumab showed promising activity in Phase II trials for patients with advanced squamous NSCLC and SCLC, improving both progression-free survival and OS.

• Anti PD-1 antibodies, nivolumab and lambrolizumab, works through the inhibition of the interaction of PD-1 and its ligands. Preliminary promising data encouraged the start of larger studies.

• Anti-PD-L1 antibodies BMS-936559 (MDX-1105) and MPDL3280A showed promising results, and they are currently being evaluated both in monotherapy and in combination with other anticancer agents.

Notes