World Lung Cancer Day: Five drug discovery breakthroughs

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This World Lung Cancer Day, DDW’s Diana Spencer takes a look at five 2023 discoveries that could transform the treatment of lung cancer in the near future.

  1. Allogeneic cell vaccines

In July 2023, Lineage Cell Therapeutics and Cancer Research UK announced encouraging primary and secondary endpoint results from their clinical study of VAC2 in advanced non-small cell lung cancer (NSCLC).

Five of eight patients treated (62.5%) had a best response of immune-related stable disease, and three (37.5%) demonstrated immune-related progressive disease.

“The unmet medical need in refractory NSCLC is significant and results from recent clinical trials support the investigation of cancer vaccines as a promising approach to treating this disease,” stated Professor Gary Middleton, Professor of Medical Oncology, Institute of Immunology and Immunotherapy, The University of Birmingham, UK.

Read more: Topline results support allogeneic cell vaccine in lung cancer

  1. Advanced stage immunotherapy

A global study, led by University College London (UCL) and University College London Hospitals (UCLH) and sponsored by Roche, showed that the cancer immunotherapy atezolizumab significantly improved the overall survival of advanced stage non-small cell lung cancer (NSCLC) patients, when compared to single-agent chemotherapy.

The study showed that atezolizumab significantly improved overall survival and resulted in a clinically meaningful long-term survival benefit, with twice as many patients (24%) who were treated with atezolizumab remaining alive at two years compared to those treated with chemotherapy (12%).

Professor Siow Ming Lee (UCL Cancer Institute and UCL Hospitals), who chaired the study Steering Committee and conceptualised the study design, said: “IPSOS is the first randomised trial to show that immunotherapy treatment with first-line atezolizumab treatment significantly improves overall survival compared to single-agent chemotherapy for these poor prognosis patients, with twice as many remaining alive at two years.”

Read more: Immunotherapy improves lung cancer long-term survival

  1. Targeted therapies

Another type of therapy showing promise in various different cancers are those that target specific genetic mutations, such as AstraZeneca’s Tagrisso (osimertinib).

Recent results from the ADAURA Phase III trial showed that osimertinib reduced the risk of death by 51% as an adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumour resection with curative intent.

Roy Herbst, Deputy Director and Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, New Haven, Connecticut, US, and principal investigator in the trial, said: “These highly anticipated overall survival results, with 88% of patients alive at five years, are a momentous achievement in the treatment of early-stage EGFR-mutated lung cancer.”

Read more: Lung cancer pill reduced risk of death by more than half

  1. Understanding the role of TREM2-expressing macrophages

In April, researchers at the Icahn School of Medicine at Mount Sinai demonstrated in a preclinical study a potential new therapeutic approach to non-small-cell lung cancer, which involves inhibiting the immune-system molecule TREM2 while enhancing natural killer cells.

During tumour progression, the researchers found that bone marrow macrophages act to suppress the recruitment and activation of natural killer cells.

Dr Merad, Director of the Precision Immunology Institute and Director of the Human Immune Monitoring Center at Icahn Mount Sinai, said: “We identified a novel axis of immunity, whereby TREM2-expressing macrophages regulate the recruitment and activity of natural killer cells during lung tumour progression, and showed preclinical evidence for a new therapeutic strategy that combines TREM2 blockade and natural killer cell activation using an antibody developed by Dr Ferrari de Andrade.”

Read more: Macrophages suppress natural killer cells in lung cancer tumours

  1. Combination therapies with immune checkpoint inhibitors

Results from the Phase III AEGEAN clinical trial showed that patients with treatment-naïve resectable non-small cell lung cancer (NSCLC) who received neoadjuvant durvalumab (Imfinzi) plus chemotherapy and adjuvant durvalumab monotherapy had improved event-free survival (EFS) and pathological complete response (pCR) compared with those who received neoadjuvant chemotherapy alone.

“We are excited to see that the trial has achieved both its primary endpoints of improving pCR and significantly reducing the likelihood of disease progression, recurrence, or death,” John Heymach, Chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, said. “The good news for patients with NSCLC is there are now multiple different regimens that have shown improvements in outcomes. This study has laid the foundation that we can build on by designing new combination regimens on top of this effective backbone.”

Read more: Therapy represents ‘new treatment paradigm’ for lung cancer

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