Difficulties on the access to innovative targeted therapies for lung cancer in Spain

Clinical and Translational Oncology https://doi.org/10.1007/s12094-023-03303-5 REVIEW ARTICLE Difficulties on the access to innovative targeted therapies for lung cancer in Spain Virginia Calvo1 · Carlos Camps2 · Enric Carcereny3 · Manuel Cobo4 · Manuel Dómine5 · María Rosario García Campelo6 · José Luis González Larriba7 · María Guirado8 · Florentino Hernando‑Trancho9 · Bartomeu Massutí10 · Ernest Nadal11 · Delvys Rodríguez‑Abreu12 · Alfredo Sánchez13 · Ivana Gabriela Sullivan14 · Mariano Provencio1 on behalf of the Spanish Lung Cancer Group (SLCG/GECP) Received: 25 July 2023 / Accepted: 2 August 2023 © The Author(s) 2023 Abstract Purpose Spanish Lung Cancer Group (SLCG) conducted a review to analyze the barriers to access to innovative targeted therapies for non-small cell lung cancer (NSCLC) in clinical practice in Spain. Methods Review all relevant content published on websites of European Commission, European Medicines Agency, and Spanish Agency of Medicines and Medical Products regarding the authorization and access to oncology treatments. Results More than 20 targeted therapies are available to treat different molecular alterations in patients with NSCLC. European Commission has approved treatments for genomic alterations involving the following genes: ALK, RET, ROS1, EGFR, BRAF, NTRK, KRAS, MET. However, the availability of these therapies in Spain is not complete, as innovative treatments are not reimbursed or funded late, with only five of these alterations currently covered by National Health System. Conclusion SLCG considers imperative to improve the access in Spain to innovative treatments for NSCLC to reduce inequity across European countries. Keywords Medicine access · Barriers · Inequity · Innovative treatments · NSCLC · Spain Introduction Lung cancer is the second leading cancer diagnosis in the United States for men (12%) or women (13%). It is the most common cause of death, accounting for 21% of estimated deaths in both sexes [1]. According to the Spanish Network of Cancer Registries (REDECAN), it is estimated that more than 30,000 new cases of lung cancer will be detected in Spain in 2023, 22,266 in men and 9016 in women, making it the third most common cancer in Spain [2]. In general, there has been a marked decrease in cancer mortality in Spain in recent decades. In the case of lung cancer, it remains the main cause of cancer death. In 2021, more than 22,000 people died of lung cancer. Mortality will * Virginia Calvo 7 Hospital Clínico San Carlos, Madrid, Spain 8 Hospital General de Elche, Alicante, Spain 1 9 Hospital Clínico San Carlos, Madrid, Spain 10 Hospital General Universitario Dr. Balmis, Alicante, Spain 11 Institut Català d’Oncologia, l’Hospitalet de Llobregat, Barcelona, Spain 12 Hospital Universitario Insular de Gran Canaria, Las Palmas, Spain 13 Consorcio Hospital Provincial, Castellón, Spain 14 Hospital Santa Creu i Sant Pau, Barcelona, Spain Oncology Department, Hospital Universitario Puerta de Hierro Majadahonda, Manuel de Falla 1, Majadahonda, 28222 Madrid, Spain 2 Hospital General Universitario, Valencia, Spain 3 Institut Català d’Oncologia, Badalona, Spain 4 Hospital Regional Universitario, Málaga, Spain 5 Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Madrid, Spain 6 Complexo Hospitalario Universitario A Coruña, A Coruña, Spain 13 Vol.:(0123456789) Clinical and Translational Oncology increase in women, mainly due to the later incorporation into smoking [2]. There are two types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), 80–85% [3]. Historically, NSCLC patients were treated with cytotoxic therapies. With the introduction of targeted and immune therapies in the last decade, there has been a dramatic improvement in survival outcomes in advanced NSCLC. Numerous oncogenic alterations have been identified in NSCLC which are considered actionable [4]. Currently, more than 20 targeted therapies are available to treat different molecular alterations across 8 genes in patients with NSCLC. The European Medical Agency (EMA) approved treatments for these molecular alterations: anaplastic lymphoma kinase (ALK) gene arrangements, rearranged during transfection (RET), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) rearrangements, epidermal growth factor receptor (EGFR) mutations, EGFR exon 20 insertions, B-RAF proto-oncogene serine/threonine kinase (BRAF) V600E, neurotrophic tyrosine receptor kinase rearrangements (NTRK), Kirsten rat sarcoma viral oncogene (KRAS), mesenchymal–epithelial transition (MET) [4, 5]. However, the availability of these treatments in Spain is not complete due to the lack of reimbursement for innovative treatments or delayed funding, only five of these driver alterations are currently covered from a therapeutic point of view (Fig. 1) [6]. In this paper, we analyzed the barriers delaying the incorporation of these innovative treatments into the Spanish National Health System (SNS). Materials and methods A literature review was conducted of all relevant content published on the websites of the European Commission (EC), the European Medicines Agency (EMA), and the Spanish Agency of Medicines and Medical Products (AEMPS) regarding the authorization of and access to oncology treatments. Results Evidence on barriers to access to innovative treatments Access to cancer care innovations will be an important metric to measure whether cancer patients have access to clinical advances. Fig. 1  Adapted from [4]. Timeline of EMA-approved targeted therapies for non-small cell lung cancer with actionable alterations. Drug availability in Spain is represented by the flag icon 13 Clinical and Translational Oncology Several reports have been published to demonstrate the level of uptake of innovation in oncology. One of the most relevant reports in terms of its history (more than 15 years) is the “EFPIA Patients W.A.I.T. Indicator Survey” [7], published bi-annually since 2004 by the European Federation of Pharmaceutical Industries and Associations (EFPIA). This document analyzes the funding situation in several European countries, allowing a comparative analysis. The access indicators analyzed are the percentage of treatment availability and the time to funding. Regarding the percentage of availability of oncology drugs, it can be observed that, compared to other European countries such as Germany, Italy, United Kingdom, and France, Spain is the country with the lowest level of access to cancer drugs approved by the EMA. Only 28% of the drugs approved by the EMA between 2018 and 2021 are fully available to patients, while 28% are available with restrictions and 41% are unavailable (Fig. 2). In terms of the time taken to adopt a pharmaceutical innovation, the average in Spain is 629 days for all medicines and 611 days for a cancer drug, making it the country with the longest time from EMA approval to adoption of the innovation among the (...truncated)