Otterson, Gregory A.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Background: Immune checkpoint inhibitors (ICIs) are a first-line and perioperative treatment for lung cancer. Pneumonitis is a potentially life-threatening complication of ICI treatment in 2% to 5% of patients; however, risk factors for developing ICI pneumonitis (ICI-p) remain undefined. Methods: We conducted a retrospective cohort study of consecutive patients with lung cancer who received at least one dose of ICI from 2015 through 2020 at The Ohio State University. Pneumonitis cases were documented by the treating oncologist and retrospectively evaluated for agreement between an oncologist and a pulmonologist. Patient demographic and clinical characteristics were recorded and summarized between those with and without pneumonitis for the overall cohort. Univariate and multivariable survival analyses using the Fine-Gray competing risk model were used to examine the associations. Results: A total of 471 patients with lung cancer were included, of which 402 had non–small cell lung cancer and 69 had small cell lung cancer; 39 (8%) patients in the overall cohort developed ICI-p. Preexisting interstitial abnormalities and prior chest radiation were both significantly associated with ICI-p on univariate analysis (hazard ratio [HR], 8.91; 95% CI, 4.69–16.92; P<.001; and HR, 2.81; 95% CI, 1.50–5.28; P=.001). On multivariable analyses, interstitial abnormalities remained a strong independent risk factor for ICI-p when controlling for chest radiation and type of immunotherapy (HR, 9.77; 95% CI, 5.17–18.46; P<.001). Among patients with ICI-p (n=39), those with severe (grade 3–5) pneumonitis had worse overall survival compared with those with mild (grade 1 or 2) pneumonitis (P=.001). Abnormal pulmonary function test results at both 12 and 18 months prior to ICI initiation were not significantly associated with ICI-p. Conclusions: Preexisting interstitial abnormalities on chest CT and prior chest radiation are independent risk factors that are strongly associated with ICI-p in patients with lung cancer. These findings highlight a potential need for closer observation for ICI-p among patients with these risk factors.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term “malignant” is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as “preferred interventions,” whereas others are categorized as either “other recommended interventions” or “useful under certain circumstances.”

Abstract Lessons Learned Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials. Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC. Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients. Background. Treatment of relapsed small-cell lung cancer (SCLC) remains suboptimal. Insulin growth factor-1 receptor (IGF-1R) signaling plays a role in growth, survival, and chemoresistance in SCLC. Linsitinib is a potent IGF-1R tyrosine kinase inhibitor that potentially may be active against SCLC. Methods. In this phase II study, 8 eligible patients were randomly assigned in a 1:2 ratio to topotecan (1.5 mg/m2 intravenously or 2.3 mg/m2 orally, daily for 5 days for 4 cycles) or linsitinib (150 mg orally twice daily until progression). The primary endpoint was progression-free survival. Patients with relapsed SCLC, platinum sensitive or resistant, performance status (PS) 0–2, and adequate hematologic, renal, and hepatic function were enrolled. Patients with diabetes, cirrhosis, and those taking insulinotropic agents were excluded. Crossover to linsitinib was allowed at progression. Results. Fifteen patients received topotecan (8 resistant, 3 with PS 2) and 29 received linsitinib (16 resistant, 5 with PS 2). Two partial responses were observed with topotecan. Only 4 of 15 patients with topotecan and 1 of 29 with linsitinib achieved stable disease. Median progression-free survival was 3.0 (95% confidence interval [CI], 1.5–3.6) and 1.2 (95% CI, 1.1–1.4) months for topotecan and linsitinib, respectively (p = .0001). Median survival was 5.3 (95% CI, 2.2–7.6) and 3.4 (95% CI, 1.8–5.6) months for topotecan and linsitinib, respectively (p = .71). Grade 3/4 adverse events (&gt;5% incidence) included anemia, thrombocytopenia, neutropenia/leukopenia, diarrhea, fatigue, dehydration, and hypokalemia for topotecan; and thrombocytopenia, fatigue, and alanine aminotransferase/aspartate aminotransferase elevations for linsitinib. Conclusion. Linsitinib was safe but showed no clinical activity in unselected, relapsed SCLC patients.