РезюмеИммунотерапия активирует иммунную систему пациента с развитием противоопухолевого иммунного ответа. В настоящее время иммуноонкологические препараты широко и успешно применяются для лечения различных видов опухолей. Критерии эффективности, применяемые при оценке химиотерапевтических препаратов, могут привести к значительным сложностям и ошибкам интерпретации ответа на иммунотерапию. Учитывая это, очень важно выбрать соответствующие критерии оценки. Целью этого обзора является освещение этой темы.

In the past century, lung cancer has become one of the most prevalent malignant neoplasms. The prognosis for patients with metastatic and locally advanced non-small cell lung cancer (NSCLC) was extremely pessimistic. The overall survival on standard platinum-based chemotherapy did not exceed 10 months. The treatment tactics choice, namely choice of specific chemotherapeutic regimen, was empirical. The situation has changed dramatically with the study of molecular-genetic disorders that contribute to a tumor development and targeted therapy availability. Until recently, the main approach to the treatment of patients with NSCLC with activating mutations was the use of first-generation tyrosine kinase inhibitors (TKI), then, in the case of disease progression, the administration of next generations drugs or chemotherapy. However, this trend has been changing lately, new generation of targeted drugs have a significant advantage in time till progression, better intracranial control, a more favorable safety profile, that establish them as first-line treatment. Recent data confirms also an improvement of overall survival. This article discusses the situation in EGFR-postive NSCLC.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) that has been approved for the treatment of metastatic non-small cell lung cancer (NSCLC) positive for the secondary T790M mutation of EGFR. Central nervous system (CNS) metastases are a common complication in patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC), resulting in a poor prognosis and limited treatment options. Almost 25% of patients present with accompanying central nervous system (CNS) metastases at the first diagnosis. Treatment of CNS metastases requires a multidisciplinary approach, and the optimal treatment options and sequence of therapies are yet to be established. Many systemic therapies have poor efficacy in the CNS due to the challenges of crossing the blood‐brain barrier (BBB), creating a major unmet need for the development of agents with good BBB‐penetrating biopharmaceutical properties. Although the CNS penetration of first‐ and second‐generation EGFR tyrosine kinase inhibitors (TKIs) is generally low, EGFR‐TKI treatment has been shown to delay time to CNS progression in patients with both in preventing or delaying the onset of CNS metastases, and in leading to intracranial response of preexisting CNS lesions. This is one of the arguments in favor of starting osimertinib upfront rather than initiating treatment with firstor second-generation EGFR-TKIs.

Immunotherapy is the most promising method in the treatment of lung cancer, especially in connection with the rapidly growing development of monoclonal antibodies aimed at inhibiting immune checkpoints: anti-CTLA-4, anti-PD-1, anti-PD-L1. Classic immuno-mediated adverse events that occur with this method of treatment can affect several organs, including the lungs. Pneumonitis is a potentially life-threatening complication and often requires rapid treatment with high doses of corticosteroids and antibacterial drugs. We present the case of a 67-year-old patient with primary multiple malignant tumors of the larynx and left lung after combined treatment and incomplete treatment with Nivolumab, complicated by immuno-mediated pneumonitis. This report highlights the importance of treating patients with contraindications to chemotherapy when specific antitumor treatment is required, as well as timely detection of a rare but dangerous adverse event: immuno-mediated pneumonitis that occurs during treatment with immune checkpoint inhibitors. Thus, knowing the frequency of adverse events when using PD-1 and PD-L1 inhibitors, as well as the possible presence of comorbidities in patients, will make it easier for doctors to make informed decisions in the treatment of patients, and understanding the interaction of the tumor and the immune system will help determine the best predictors of response and further improve the results of treatment of patients with NSCLC.

The EGFR gene mutation occurs in 15% of patients with NSCLC. Tumors with such a molecular genetic profile are characterized by high sensitivity to therapy with EGFR tyrosine kinase inhibitors. However, the majority of EGFRm+ patients develop resistance to 1-2 generation TKI therapy after 9-13 months. In our study, we considered an integrated regimen combined use chemotherapy and targeted therapy as a possible way to overcome acquired tumor resistance to TKIs of 1–2 generations. The study included patients with IIIB / IV stages of NSCLC with activating EGFR mutations.  Initially there were two months of treatment by gefitinib 250 mg daily. Then, after a 2-week drug-free period, 3 cycles of paclitaxel 175 mg / m2 and carboplatin AUC5 were administrated at days 71-113. Thereafter, gefitinib was re-started on day 135 and continued until disease progression. The median PFS was 20.- months (16.0-23.9 months, CI 95%).  One -year progression-free survival (PFS) in patients who completed the chemotherapy stage was 79,6 %, two-year PFS - 38,9%. Brain metastases among patients with a progression of the disease were observed in 12 people (28.6%). The data obtained confirm the promise of using integrated chemotherapy with TKIs as a way to overcome the development of acquired resistance to TKIs of 1–2 generations.