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Practical Issues in the Use of Atezolizumab for Patients with Non-Small Cell Lung Cancer: Case Reports and Literature Review.

ABSTRACT: Atezolizumab is a monoclonal antibody targeting the programmed death ligand 1 (PD-L1) that was approved in 2017 in the USA and Europe for the second-line treatment of advanced or metastatic non-small cell lung cancer (NSCLC). This review article describes the practical clinical issues associated with atezolizumab treatment in NSCLC using a combination of four illustrative cases and a narrative literature review. The first two cases highlight the importance of tumor mutational status when making treatment decisions. A 62-year-old man with epidermal growth factor receptor (EGFR)-mutated, PD-L1-positive, stage IV lung adenocarcinoma received treatment with second-line atezolizumab + bevacizumab, carboplatin, and paclitaxel (BCP) after first-line osimertinib. In the second case, a 63-year-old man with stage IVb lung adenocarcinoma with anaplastic lymphoma kinase (ALK) translocation received sixth-line treatment with atezolizumab + BCP. The two final cases both had extensive metastases. A 55-year-old woman with EGFR-mutated lung adenocarcinoma received second-line treatment with atezolizumab + BCP after development of multiple metastases, followed by atezolizumab + bevacizumab until last follow-up. A 42-year-old man with PD-L1-positive pulmonary adenocarcinoma (negative for EGFR mutations) developed liver and brain metastases after several lines of therapy. He underwent holocranial radiation and received atezolizumab + BCP, which resulted in a decrease in all measurable and evaluable tumoral lesions. These illustrative cases indicate that the type and number of mutations may influence treatment response to atezolizumab, and that atezolizumab may provide clinical benefit in patients with high disease burden.

SUBMITTER: Cobo M

PROVIDER: S-EPMC8140026 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The era of immunotherapy has changed the face of how we approach treatment for many oncologic and hematologic malignancies. Lung cancer has been in the forefront of checkpoint inhibition for the past 2 years and has paved the path for other subspecialties. While PD-1 inhibitors nivolumab and pembrolizumab have been approved for non-small cell lung cancer (NSCLC), this review focuses on atezolizumab, its landmark studies, and ongoing trials. Atezolizumab is the first programmed death ligand 1 (PD-L1) inhibitor to receive US Food and Drug Administration (FDA) approval for metastatic NSCLC patients who have progressed on frontline chemotherapy. This approval was based on two open-label Phase II multicenter trials, POPLAR (NCT01903993) and BIRCH (NCT02031458). Both studies revealed a benefit in overall survival (OS), progression-free survival, and response rate in the atezolizumab arm when compared to single-agent docetaxol. There were also fewest Grade 3-5 treatment-related adverse events (TRAEs) in the atezolizumab cohort. The open-label randomized Phase III OAK trial (NCT02008227) further established the role of atezolizumab in previously treated NSCLC. This study compared atezolizumab with docetaxel in patients with advanced NSCLC (squamous or nonsquamous histologies) who had progressed on one to two prior chemotherapy regimens. OS in the PD-L1-enriched population was superior in the atezolizumab arm (n=241) at 15.7 months compared with docetaxel (n=222) at 10.3 months (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.58-0.93; p=0.0102). Patients lacking PD-L1 also had survival benefit with atezolizumab with a median OS (mOS) of 12.6 months versus 8.9 months with chemotherapy (HR 0.75, 95% CI 0.59-0.96). Benefit was noted in both squamous and nonsquamous NSCLC subsets and regardless of PD-L1 expressivity. As seen in the POPLAR and BIRCH studies, the toxicity profile was significantly better with immunotherapy. The future is unfolding rapidly as new checkpoint inhibitors are gaining FDA approval. It is still not known if these agents will be used in combination with chemotherapy, with other immune-modulating agents, radiation therapy, or all of the above. The results of these studies investigating their use in combination with chemotherapy agents, with other immunotherapy agents such as CTLA-4 inhibitors, and with radiation therapy, are eagerly awaited.

Project description:BackgroundImmune checkpoint inhibitors (ICIs), an enormous oncological breakthrough in the last 10 years, have become the standard treatments for several types of solid cancers. Although ICIs are generally well tolerated and result in favorable outcomes, they also cause unique immune-related adverse events (irAEs) across bodily systems and organs. Compared to most common irAEs, which occur in the endocrine, skin, pulmonary system, and gastrointestinal tract, haematological irAEs (haem-irAEs) are relatively rare but potentially life-threatening events that are occasionally irreversible and refractory. Currently, haem-irAEs are not sufficiently understood, management, and lack consensus, while other common irAEs have well been characterized and managed. The reports of ICI-related thrombocytopenia in small cell lung cancer (SCLC) are rarely seen. Hence, we reported a rare case of severe steriod-resistant ICI-related thrombocytopenia after received chemotherapy plus anti-PD-L1 inhibitor in SCLC patient. Our case exemplifies the diagnosis, diagnosis of exclusion, treatment, and prognosis of thrombocytopenia in the pattern of combination therapy, meanwhile, the subject of diagnosis, therapies, therapeutic strategies for refractory type and incidence, potential biomarkers, mechanisms and prognosis in ICI-related thrombocytopenia have been fully discussed.Case descriptionHerein, we present a 64-year-old man diagnosed advanced SCLC developed refractory immune-related severe thrombocytopenia, who achieved favorable outcomes of cancer following chemotherapy combined with atezolizumab administrated. Routine blood re-examination on the third day of 6th therapy showed a thrombocyte count of 11×109/L. Combined the medical history and the results of laboratory tests, the diagnosis of ICI-induced thrombocytopenia was confirmed. Despite large doses of methylprednisolone, immunoglobulin, and rituximab, intermittent platelet transfusion, thrombopoietin being administrated to the patient, there were no signs of platelet count and hemoglobin improvement. Currently, this is the first case about atezolizumab induced thrombocytopenia in SCLC patient, while there is extremely rare haem-irAEs reported in SCLC.ConclusionsAlthough ICI-related severe thrombocytopenia is rare, it may persist or even be fatal. Clinicians should pay more attention to its diagnosis and prompt treatment. Once developed thrombocytopenia, large doses of methylprednisolone, ntermittent platelet transfusion, thrombopoietin should be timely administrated, also plasma exchange or rilzabrutinib, other immunosuppressive drugs, or IL-6 inhibitor warrant apply if steriod-resistant.

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Practical Issues in the Use of Atezolizumab for Patients with Non-Small Cell Lung Cancer: Case Reports and Literature Review.

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