J. Vansteenkiste MD, PhD

Rethinking the reimbursement of innovative medicines in oncology: Looking beyond overall survival

SUMMARY

The oncological treatment landscape is evolving at a very rapid pace with a continuous stream of novel treatment options. To fully leverage these therapeutic advances in clinical practice it is important to facilitate a rapid access to innovative anticancer drugs for patients. Specifically for Belgium, the delay from EMA approval to reimbursement for anticancer drugs is very long, with an average of almost 600 days, and a substantial proportion of innovative drugs never make it to the patient. The stringent focus of the Belgian Commission for Reimbursement of Medicines (CRM) on overall survival (OS) data in reimbursement decisions is believed to be an important contributor to this situation. However, the ever-increasing pace at which new anticancer therapies are being developed in combination with an earlier detection of cancer will make it increasingly difficult to present mature OS data at the time of regulatory approval in the years to come. As such, there is an urgent need for a debate with the regulators to consider more readily available endpoints in their reimbursement assessments. In fact, when a strong treatment effect is seen on an intermediate endpoint such as disease-free or progression-free survival, a benefit in OS is quite likely. As such, our reimbursement system needs to be adapted to better align with the scientific progress in oncology. In this, a temporary reimbursement decision based on intermediate endpoints could give Belgian patients earlier access to promising lifesaving medicines. In this, we as oncologists, including specialists in haematology, respiratory oncology, and gastrointestinal cancer, strongly encourage the CRM to use the grading provided by the ESMO magnitude of clinical benefit scale to evaluate the clinical added value of future cancer treatments. This will not only facilitate a faster patient access to innovative therapies, but will also help policy-makers in advancing ‘accountability for reasonableness’ in their resource allocation deliberations.

(BELG J MED ONCOL 2023;17(6):211–5)

Highlights in respiratory oncology

Summary

ASCO 2020 featured the presentation of many interesting studies in the field of lung cancer. For early stage non-small cell lung cancer (NSCLC), there was a focus on adjuvant targeted therapy while for advanced NSCLC without oncogene addiction much attention went to first-line immunotherapy and to the use of novel antibody-drug conjugates. In addition to this, several trials discussed the potential of EGFR-tyrosine kinase inhibitor (TKI) combinations, the targeting of MET alterations or RET fusions and the search for EGFR exon 20 mutant selective drugs for patients with advanced NSCLC and oncogene addictions. Finally, this overview will describe important results in the field of non-metastatic and metastatic small-cell lung cancer (SCLC) as well as advances in mesothelioma.

(BELG J MED ONCOL 2020;14(5):201-8)

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)