US Food and Drug Administration Approval Summary: Nivolumab Plus Platinum-Doublet Chemotherapy for the Neoadjuvant Treatment of Patients With Resectable Non-Small-Cell Lung Cancer.

PURPOSE: On March 4, 2022, the US Food and Drug Administration (FDA) approved nivolumab plus platinum-doublet chemotherapy for the neoadjuvant treatment of patients with resectable non-small-cell lung cancer (NSCLC). We discuss the FDA's review of the key data and regulatory considerations supporting this approval. PATIENTS AND METHODS: The approval was based on the results of CheckMate 816, an international, multiregional, active-controlled trial that randomly assigned 358 patients with resectable NSCLC, stage IB (≥4 cm) to IIIA (N2) per the American Joint Committee on Cancer seventh staging edition to receive either nivolumab plus platinum-doublet or platinum-doublet chemotherapy alone for three cycles before planned surgical resection. The major efficacy end point that supported this approval was event-free survival (EFS). RESULTS: At the first planned interim analysis (IA), the hazard ratio (HR) for EFS was 0.63 (95% CI, 0.45 to 0.87; P = .0052; statistical significance boundary = .0262) favoring the nivolumab plus chemotherapy arm; the median EFS was 31.6 months (95% CI, 30.2 to not reached) in the nivolumab plus chemotherapy arm versus 20.8 months (95% CI, 14.0 to 26.7) in the chemotherapy-only arm. At the time of a prespecified IA for overall survival (OS), 26% of patients had died, and the HR for OS was 0.57 (95% CI, 0.38 to 0.87; P = .0079; statistical significance boundary = .0033). Eighty-three percent of patients in the nivolumab-containing arm versus 75% in the chemotherapy-only arm received definitive surgery. CONCLUSION: This approval, the first for any regimen for the neoadjuvant treatment of NSCLC in the United States, was supported by a statistically significant and clinically meaningful improvement in EFS with no evidence of detriment in OS or negative impact on patients' receipt and timing of surgery or surgical outcomes.

FDA Approval Summary: Pembrolizumab, Atezolizumab, and Cemiplimab-rwlc as Single Agents for First-Line Treatment of Advanced/Metastatic PD-L1-High NSCLC.

FDA's approval of cemiplimab-rwlc on February 22, 2021, follows prior approvals of pembrolizumab and atezolizumab for similar indications as first-line treatment for patients with programmed death ligand-1 (PD-L1)-high advanced non-small cell lung cancer (NSCLC). Approvals of these anti-PD-L1 agents were supported by statistically significant and clinically meaningful improvements in overall survival (OS) in international, multicenter, active-controlled randomized trials. In KEYNOTE-024, the OS HR was 0.60 [95% confidence interval (CI), 0.41-0.89; P = 0.005] favoring pembrolizumab over platinum-doublet chemotherapy. In IMpower110, the OS HR was 0.59 (95% CI, 0.40-0.89; P = 0.0106) favoring atezolizumab over platinum-doublet chemotherapy. In Study 1624, the OS HR was 0.68 (95% CI, 0.53-0.87; P = 0.0022) favoring cemiplimab-rwlc over platinum-doublet chemotherapy. The progression-free survival (PFS) effect sizes for these anti-PD-L1 antibodies were also comparable across their respective registrational trials, and their safety profiles were consistent with the anti-PD-L1 class adverse event profile. The consistent survival benefits and manageable toxicity profiles of these single-agent anti-PD-L1 antibodies have established them as important treatment options in the PD-L1-high NSCLC treatment landscape. FDA approvals of these anti-PD-L1 antibodies, based on their favorable benefit-risk profiles, present effective chemotherapy-free therapeutic options for patients with advanced PD-L1-high NSCLC in the United States.

FDA Approval Summary: Capmatinib and Tepotinib for the Treatment of Metastatic NSCLC Harboring MET Exon 14 Skipping Mutations or Alterations.

The FDA approved capmatinib and tepotinib on May 6, 2020, and February 3, 2021, respectively. Capmatinib is indicated for patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors have a mutation leading to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. Tepotinib is indicated for mNSCLC harboring MET exon 14 skipping alterations. The approvals were based on trials GEOMETRY mono-1 (capmatinib) and VISION (tepotinib). In GEOMETRY mono-1, overall response rate (ORR) per Blinded Independent Review Committee (BIRC) was 68% [95% confidence interval (CI), 48-84] with median duration of response (DoR) 12.6 months (95% CI, 5.5-25.3) in 28 treatment-naïve patients and 41% (95% CI: 29, 53) with median DoR 9.7 months (95% CI, 5.5-13) in 69 previously treated patients with NSCLC with mutations leading to MET exon 14 skipping. In VISION, ORR per BIRC was 43% (95% CI: 32, 56) with median DoR 10.8 months (95% CI, 6.9-not estimable) in 69 treatment-naïve patients and 43% (95% CI, 33-55) with median DoR 11.1 months (95% CI, 9.5-18.5) in 83 previously-treated patients with NSCLC harboring MET exon 14 alterations. These are the first two therapies to be FDA approved specifically for patients with metastatic NSCLC with MET exon 14 skipping.

Electronic Cigarette Use among Survivors of Smoking-Related Cancers in the United States.

BACKGROUND: The prevalence of electronic cigarette (e-cigarette) use and its impact on smoking cessation among cancer survivors in the United States is largely unknown. We sought to estimate the prevalence of e-cigarette use and examine its associations with cigarette smoking and smoking quit attempts among smoking-related cancer survivors in the United States. METHODS: We obtained data from the 2014-2017 annual cycles of the National Health Interview Survey for participants with self-reported history of smoking-related cancer(s). We calculated the prevalence of current e-cigarette use and utilized multinomial logistic regression in examining the independent association between e-cigarette use and cigarette smoking. Appropriate survey weights were applied in estimating the prevalence rates, relative risk ratios (RRR), ORs, and confidence intervals (CI). RESULTS: Our sample comprised 3,162 smoking-related cancer survivors. The prevalence of current e-cigarette use was 3.18% (95% CI, 2.40-3.96). Current e-cigarette users were 83 times as likely as never users to be current cigarette smokers (RRR, 82.89; 95% CI, 16.54-415.37). Among those with a history of cigarette smoking, current e-cigarette users were 90% less likely to be former smokers (OR, 0.10; 95% CI, 0.05-0.18). No association was seen between current e-cigarette use and a smoking quit attempt in the prior year. CONCLUSIONS: E-cigarette use among cigarette ever smokers was associated with a lower likelihood of being a former smoker/having quit smoking, and e-cigarette use was not associated with smoking quit attempts. IMPACT: Our findings do not provide evidence that e-cigarette use facilitates smoking cessation among smoking-related cancer survivors.

Cyclin-Dependent Kinase 4/6 Inhibitor (Palbociclib) Induced Aplastic Anemia in a Patient with Metastatic Breast Cancer.

Breast cancer is the most common cancer diagnosed in women worldwide. Over the years, breast cancer treatment has undergone revolutionary changes especially for women with hormone receptor positive metastatic disease. As a result, women are living longer with their disease, particularly in developed countries. The use of cyclin-dependent kinase (CDK) 4/6 inhibitors with antiestrogen therapy is a relatively new therapeutic option which has been shown to improve progression-free survival. Hematologic adverse events, most frequently neutropenia, are well-known side effects of CDK 4/6 inhibitors. However, to our knowledge, aplastic anemia has never been reported. We report a case of aplastic anemia in a patient with metastatic breast cancer treated with palbociclib after multiple prior lines of therapy.

Secondhand Smoke Exposure Among Community-Dwelling Adult Cancer Survivors in the United States: 1999-2012.

Background: Little is known about the prevalence of secondhand smoke exposure (SHSe) among cancer survivors. We sought to determine the prevalence, trends, and correlates of SHSe among nonsmoking adult cancer survivors in the United States.Methods: Interview and serum cotinine data for nonsmoking adults, age 20 years and older, with a history of cancer (N = 686) were obtained from consecutive two-year cross-sectional cycles of the National Health and Nutrition Examination Survey from 1999 to 2012. SHSe was defined as serum cotinine 0.05-10 ng/mL among nonsmokers. We calculated and trended the prevalence of SHSe among nonsmoking cancer survivors. Multivariable logistic regression was used to examine the associations of SHSe with sociodemographic, smoking, and clinical characteristics. Survey weights were applied in estimating prevalence rates, adjusted ORs, and confidence intervals (CI).Results: The weighted aggregate SHSe and self-reported indoor SHSe prevalence rates over the study period were 28.26% (95% CI: 24.97%-31.55%) and 4.53% (95% CI: 3.48%-5.57%), respectively. SHS exposure declined from 39.61% (95% CI: 27.88%-51.34%) in 1999/2000 to 15.68% (95% CI: 9.38%-21.98%) in 2011/2012 (Ptrend < 0.001). Age ≥ 60 years was protective against SHSe, while being black, having less than high school education, poverty, and a smoking-related cancer history were associated with higher odds of SHSe.Conclusions: Fortunately, SHSe among nonsmoking cancer survivors in the United States is on the decline, although certain subgroups remain disproportionately burdened.Impact: These findings highlight clinical and public health imperatives to target socioeconomically disadvantaged nonsmoking cancer survivors to reduce their SHSe. Cancer Epidemiol Biomarkers Prev; 26(8); 1296-305. ©2017 AACR.

Racial and Ethnic Disparities in Health and Health Care: an Assessment and Analysis of the Awareness and Perceptions of Public Health Workers Implementing a Statewide Community Transformation Grant in Texas.

INTRODUCTION: Little is known about the awareness of public health professionals regarding racial and ethnic disparities in health in the United States of America (USA). Our study objective was to assess the awareness and perceptions of a group of public health workers in Texas regarding racial health disparities and their chief contributing causes. METHODS: We surveyed public health professionals working on a statewide grant in Texas, who were participants at health disparities' training workshops. Multivariable logistic regression was employed in examining the association between the participants' characteristics and their perceptions of the social determinants of health as principal causes of health disparities. RESULTS: There were 106 respondents, of whom 38 and 35 % worked in health departments and non-profit organizations, respectively. The racial/ethnic groups with the highest incidence of HIV/AIDS and hypertension were correctly identified by 63 and 50 % of respondents, respectively, but only 17, and 32 % were knowledgeable regarding diabetes and cancer, respectively. Seventy-one percent of respondents perceived that health disparities are driven by the major axes of the social determinants of health. Exposure to information about racial/ethnic health disparities within the prior year was associated with a higher odds of perceiving that social determinants of health were causes of health disparities (OR 9.62; 95 % CI 2.77, 33.41). CONCLUSION: Among public health workers, recent exposure to information regarding health disparities may be associated with their perceptions of health disparities. Further research is needed to investigate the impact of such exposure on their long-term perception of disparities, as well as the equity of services and programs they administer.