Predictive factors testing proposal for NSCLC patients during the COVID-19 pandemic

Abstract

In all countries in the world as well as Poland, there are no recommendations regarding the testing of predictive factors qualifying non-small cell lung cancer (NSCLC) patients for molecularly targeted therapies and for immunotherapy at the time of the COVID-19 (Coronavirus Disease 2020) pandemic. Predictive factors testing (essentially mutations in EGFR, BRAF, MET genes, rearrangement of ALK, ROS1, NTRK genes, and PD-L1 protein expression) is necessary for systemic treatment arrangement in patients with locally advanced and advanced NSCLC. When a driver alteration is detected, treatment with the appropriate targeted therapy radically changes patient prognosis. The Lung Cancer Mutation Consortium has shown that actionable drivers could be detected in 64% of lung adenocarcinomas [1]. Therefore, there should be no question of postponing the examination of predictors and systemic treatment due to the prevailing COVID-19 pandemic. Molecularly targeted therapies and immunotherapy are the most effective systemic treatments in locally advanced and metastatic NSCLC patients in whom predictors have been detected. All recommendations indicate that NSCLC patients with stage IIIB or IV should immediately qualify for the above treatment [2]. Thus, rapid and effective diagnosis of predictive factors, whose presence qualifies patients for personalized therapies, should be unobstructed in patients with NSCLC during the COVID-19 pandemic [3]. Summary of predictive factors testing proposal during COVID-19 pandemis is presented in Figure 1. Meanwhile, statistical analysis provided by Diaceutics Company has indicated that only in the UK in March 2020, 31% fewer patients with lung cancer were diagnosed compared with previous months. Furthermore, the percentage of patients who were tested for EGFR gene mutations decreased by 13%. Two reasons are speculated for this phenomenon. Firstly, impaired admittance of lung cancer patients to diagnostics procedures (including primarily bronchoscopy methods), and secondly, changing the profile of genetic laboratories that have started SARS-CoV-2 diagnostics [4]. Moreover, Malapelle et al. compared 4 weeks of national lockdown from seven different European countries to a corresponding period in 2019 in terms of molecular test workload. Most laboratories (80%) showed a variable reduction in the number of tissue samples analyzed [5]. It could be assumed that the great restrictions introduced to accessing specialized medical services in Polish hospitals, resulted in the reducing percentage of newly diagnosed lung cancer patients, as it was observed in many European countries. The indisputable need for predictive tests and continuation of molecularly targeted therapies during the COVID-19 pandemic was confirmed in a Chinese (from Hubei province) NSCLC patient diagnosed with EGFR mutation. In February 2016, the patient had begun gefitinib therapy after diagnosis of Leu858Arg mutation in the EGFR gene. Response to treatment lasted until September 2017, when a Thr790Met resistance mutation in EGFR gene was detected. Afterward, the patient began treatment with osimertinib. Radiation therapy for the area of enlarged mediastinal lymph nodes was also applied. In January 2020, the patient developed fever, cough, shortness of breath, diarrhea, and myalgia. Genetic tests confirmed the presence of SARS-CoV-2. Treatment based on cefoselis , oseltamivir, meropenem, teicoplanin and moxifloxacin, followed by lopinavir and ritonavir was admitted immediately with acceptable effect, which led to a continuation of osimertinib therapy. Finally, chest changes were controlled, and stabilization of lung cancer was achieved [6]. It is now well documented that patients with cancer who develop COVID-19 have a high probability of mortality. Appropriate and aggressive preventive measures must be taken to reduce the risk of COVID-19 in patients with cancer and to optimally manage those who do contract the infection [7]. A complicated situation regarding the use of immune checkpoint inhibitors (anti-PD-1 or anti-PD-L1 monoclonal antibodies) in NSCLC patients during COVID-19 pandemic. This is due to the fact that the anticancer immunotherapy activates the immune system, and severe course of COVID-19 results from excesive immune system and a cytokine storm. Therefore, clinicians are concerned about the use of immunotherapy during the COVID-19 pandemic. Interstitial pneumonia in the course of COVID-19 and pulmonary toxicities of immunotherapy have a very similar immune background.