Introduction

Lung cancer is the leading cause of cancer-related death and the second most common malignancy in the world [1]. NonSmall Cell Lung Cancer (NSCLC) accounts for approximately 85 percent of newly diagnosed lung cancer cases [2]. Survival after diagnosis has improved, due to screening and treatment advances. In patients with advanced NSCLC, the tumor should be screened for the presence of driver mutations. The identification of oncogenic drivers, particularly the Epidermal Growth Factor Receptor (EGFR), the Anaplastic Lymphoma Kinase (ALK) gene, the c-ROS oncogene 1 (ROS1) and the B-Raf Proto-Oncogene (BRAF), has led to the development of specific targeted therapies for patients [3]. Other driver mutations have also been identified and specific targeted treatments are being developed. Matching a specific targeted drug to the identified mutation profile has resulted in improved therapeutic efficacy, often in combination with reduced toxicity.

Kirsten Rat Sarcoma Virus (KRAS) mutations are observed in up to 30 percent of lung adenocarcinomas [3]. For patients with advanced NSCLC with a KRAS G12C mutation who have progressed on a previous line of therapy, sotorasib is indicated. Sotorasib is an irreversible inhibitor of KRAS G12C, and has shown promising anticancer activity in a phase 1 study in patients with KRAS G12C-mutated advanced solid tumors [4]. Furthermore, in a randomized, open-label, phase 3 trial among 345 patients with advanced NSCLC with KRAS G12C mutation who experienced progression on previous anticancer therapy, sotorasib, compared with docetaxel, showed significantly greater progression-free survival and significantly fewer serious treatment-related adverse events [5]. However, sotorasib has some important drug-drug interactions and should not be co-administered with proton pump inhibitors and H2-receptor antagonists [6]. Sotorasib is also a strong Cytochrome P450 3A4 (CYP3A4) inducer and co-administration with a CYP3A4 substrate decreases the plasma concentrations of the substrate, which may reduce their efficacy. Therefore, coadministration of sotorasib with a CYP3A4 substrate should be avoided.

Bone metastases are a common manifestation of distant relapse from many types of solid tumors, especially those arising in the lung, breast, prostate, and kidney, and they represent a prominent source of morbidity [7]. Metastatic bone disease causes pain by several mechanisms, namely structural disruption, inflammatory mediator release, and changes in sensory innervation. Pharmacological treatment guidelines for cancer-related pain are in line with the World Health Organization (WHO) “three-step ladder” algorithm, in which opioids have been the cornerstone of pharmacologic treatment of cancer pain for the last decades. It is important to note that many opioids are metabolized primarily by the CYP3A4 enzyme. Thus, co-administration of sotorasib and opioids could potentially have disastrous consequences.

Case Presentation

A 62-year-old female patient with a history of hypertension, transient ischemic attack, chronic hip pain and advanced NSCLC was referred to our university hospital for a possible inclusion in a clinical trial studying novel treatment options for NSCLC. She had previously received immunotherapy (durvalumab), chemotherapy (carboplatin and gemcitabine) and radiation therapy. Despite the previous treatment, she had a persistent slow progression of the disease.

Her score on the Eastern Cooperative Oncology Group Scale of Performance Status was 1 at referral. Her physical examination was normal. Blood tests revealed hemoglobin of 6.3 mmol/L, creatinine 80