J. Vansteenkiste MD, PhD

Highlights in respiratory oncology

In this article, the ten key messages with respect to thoracic oncology presented at ASCO 2019, are summarized.

Highlights in respiratory oncology

This article will briefly discuss the top stories in the field of respiratory oncology presented during the 2018 annual meeting of the American Society of Clinical Oncology (ASCO). For a complete overview of abstracts we refer to the official meeting website: https://am.asco.org.

Second-line treatment of non-small cell lung cancer adenocarcinoma patients not harbouring an oncogene driver mutation anno 2017–2018: A consensus group meeting

Summary

The treatment landscape for patients with advanced non-small cell lung cancer, who do not harbour an oncogenic driver abnormality, has changed dramatically over the last years. Second-generation antiangiogenic agents, such as nintedanib and ramucirumab, and particularly PD-1/PD-L1 inhibitors, such as nivolumab, pembrolizumab and atezolizumab have shown to prolong survival in pretreated non-small cell lung cancer patients. Immune checkpoint inhibition in the treatment of advanced non-small cell lung cancer comes with the promise of durable responses in responding patients. Nevertheless, one must appreciate that the average response rate seen with these PD-1/PD-L1 targeting agents is only about 20%. While PD-L1 testing may be used as an enrichment biomarker, a substantial proportion of patients still do not benefit from these agents. They could benefit from alternative therapeutic options, including novel anti-angiogenic agents. In this paper, a treatment algorithm is proposed that aims to optimise the second-line treatment choice for patients with lung adenocarcinoma, based on the available clinical data.

(BELG J MED ONCOL 2018;12(2):61–66)

Will there ever be a lung cancer vaccine?

SUMMARY

Current treatment options for advanced stage non-small cell lung cancer (NSCLC) include chemotherapy and targeted therapy. Immunotherapy is the most recent strategy to improve survival in NSCLC. Among other newly developed immunotherapeutics, all aiming to enhance and reinforce the natural ability of the immune system to fight cancer, lung cancer vaccines aim to increase the number of tumor-reactive T-cells. Although preclinical models have shown that vaccines enhance effector T-cell infiltration into the tumor, this effect has not been translated into clinical benefit in multiple, large, randomised, placebo-controlled studies. Recent understanding of cancer immunology has shown that the immunosuppressive microenvironment of NSCLC is able to inactivate the tumor-reactive T-cells generated by therapeutic vaccination.

Consequently, combining vaccination with other immunotherapeutics to reverse this immunosuppressive environment (such as anti-PD-1/PD-L1) seems to be the best way forward.

Furthermore it will be important to develop relevant biomarkers to choose the most adequate combination of immunotherapeutics for each individual patient, because of the diverse mechanisms of immunosuppression by the tumor.

(BELG J MED ONCOL 2017;11(6):255–258)

Therapy-orienting testing of EGFR inhibitor-resistant non-small cell lung cancer

SUMMARY

Somatic sensitising mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are detected in approximately 10% of patients with advanced non-squamous non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the first-line treatment option for patients with an actionable EGFR mutation. Despite initial responses, the majority of patients progress within one to two years after EGFR-TKIs treatment initiation.

The most common mechanism of resistance is the development of an additional EGFR-T790M mutation in exon 20, found in 50–60% of EGFR-mutant NSCLC patients who were rebiopsied on EGFR-TKI treatment. Phase II and III trials with osimertinib, a third-generation EGFR-TKI, demonstrated an objective response rate (ORR) of 60–70% and median progression-free survival (mPFS) of 10–11 months in EGFR-T790M-positive tumours.

A tissue biopsy of a progressing lesion for confirmation of histology and molecular characterisation is a critical consideration. However, a repeat tissue biopsy is not possible for every patient. Therefore, a liquid biopsy can be considered for EGFR-T790M mutation testing. Indeed, clinical trials testing osimertinib have shown similar clinical outcomes (ORR and mPFS on osimertinib) in patients with T790M-positive plasma versus T790M-positive tumour tissue.

Osimertinib clearly expands relapse treatment options for advanced stage EGFR-mutant NSCLC. Testing for EGFR-T790M at acquired resistance should become a standard component of patient care in EGFR-mutant tumours. In this manuscript, we propose and discuss two possible clinical diagnostic algorithms that could be used for the therapy-orienting testing of EGFR-TKI-resistant NSCLC patients. Tissue and liquid biopsies involve challenges in terms of specific clinical role, safety, logistics, and cost.

(BELG J MED ONCOL 2017;11(5):226–233)

Highlights in respiratory oncology

At ASCO 2017, 195 abstracts in the feld of respiratory oncology were presented (169 in 2016): 22 oral presentations (including 4 in a clinical science symposium), 24 poster discussion items, and 149 posters. In this summary, most attention will go to phase III randomized controlled trials (RCTs) and innovative data that are, or may become, relevant for the practicing clinician. As this report is only the “extract of the abstracts”, the reader is referred to the respective abstracts published in J Clin Oncol volume 35 Suppl 15, 2017 (abstracts #8500–8586 and #9000–9107 and available on-line at https://meetinglibrary.asco.org/

Immunotherapy in lung cancer: current approach and clinical application

Since its start in 2009, immunotherapy with immune checkpoint inhibitors has become a hot topic in respiratory oncology. Randomized controlled trials have proven the superiority of immune checkpoint inhibitor therapy versus standard chemotherapy in advanced non-small cell lung cancer (NSCLC). PD-L1 immunohistochemistry (IHC) is so far the most commonly implemented predictive biomarker in the selection of optimal candidates for immunotherapy. Immunotherapy with pembrolizumab is approved in first-line for advanced NSCLC with a PD-L1 expression on >50% of tumor cells, and after at least one prior chemotherapy regimen in case of PD-L1 expression of >1%. Treatment with nivolumab or with atezolizumab is approved for advanced NSCLC after prior chemotherapy, irrespective of the PD-L1 status. Since PD-L1 expression does not always correlate with treatment efficacy, other biomarkers are under investigation. Tumor mutational burden (which correlates clinically with smoking status) and CD8 tumor-infiltrating lymphocytes are associated with increased responsiveness to PD-L1 inhibition, and thus are other promising predictive biomarkers. NSCLC with molecular drivers on the contrary is preferably treated with tyrosine kinase inhibitors (TKIs) rather than immunotherapy due to lower response rates, even in case of high PD-L1 expression. Immunotherapy and other therapeutic modalities (chemotherapy, radiotherapy, TKIs) might work in synergy. The results of the first prospective trials with combination therapy were recently published, and many others are to be expected.