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Lung cancer is the leading cause of cancer-related death worldwide. However, lung cancer incidence and mortality rates differ substantially across the world, reflecting varying patterns of tobacco smoking, exposure to environmental risk factors and genetics. Tobacco smoking is the leading risk factor for lung cancer. Lung cancer incidence largely reflects trends in smoking patterns, which generally vary by sex and economic development. For this reason, tobacco control campaigns are a central part of global strategies designed to reduce lung cancer mortality. Environmental and occupational lung cancer risk factors, such as unprocessed biomass fuels, asbestos, arsenic and radon, can also contribute to lung cancer incidence in certain parts of the world. Over the past decade, large-cohort clinical studies have established that low-dose CT screening reduces lung cancer mortality, largely owing to increased diagnosis and treatment at earlier disease stages. These data have led to recommendations that individuals with a high risk of lung cancer undergo screening in several economically developed countries and increased implementation of screening worldwide. In this Review, we provide an overview of the global epidemiology of lung cancer. Lung cancer risk factors and global risk reduction efforts are also discussed. Finally, we summarize lung cancer screening policies and their implementation worldwide.Lung cancer is the commonest cancer globally. Reflecting patterns of smoking and other risk factor exposures, both the incidence of and mortality from lung cancer are highest in economically developed countries. Nonetheless, developing and less economically developed countries are likely to have the biggest increases in lung cancer in the coming years. In this Review, the authors describe the global epidemiology of lung cancer, and how changes in exposures, socioeconomic status, public health interventions and better treatment strategies are influencing both the incidence of and mortality from lung cancer.

Randomized controlled trials (RCTs) have demonstrated a survival benefit for adjuvant platinum-based chemotherapy after resection of locoregional non-small cell lung cancer (NSCLC). The relative benefits and harms and optimal approach to treatment for NSCLC patients who have major comorbidities (chronic obstructive pulmonary disease [COPD], coronary artery disease [CAD], and congestive heart failure [CHF]) are unclear, however. We used a simulation model to run in-silico comparative trials of adjuvant chemotherapy versus observation in locoregional NSCLC in patients with comorbidities. The model estimated quality-adjusted life years (QALYs) gained by each treatment strategy stratified by age, comorbidity, and stage. The model was parameterized using outcomes and quality-of-life data from RCTs and primary analyses from large cancer databases. Adjuvant chemotherapy was associated with clinically significant QALY gains for all patient age/stage combinations with COPD except for patients >80 years old with Stage IB and IIA cancers. For patients with CHF and Stage IB and IIA disease, adjuvant chemotherapy was not advantageous; in contrast, it was associated with QALY gains for more advanced stages for younger patients with CHF. For stages IIB and IIIA NSCLC, most patient groups benefited from adjuvant chemotherapy. However, In general, patients with multiple comorbidities benefited less from adjuvant chemotherapy than those with single comorbidities and women with comorbidities in older age categories benefited more from adjuvant chemotherapy than their male counterparts. Older, multimorbid patients may derive QALY gains from adjuvant chemotherapy after NSCLC surgery. These results help extend existing clinical trial data to specific unstudied, high-risk populations and may reduce the uncertainty regarding adjuvant chemotherapy use in these patients.

Background It has been postulated that patient’s sex impacts response to immunotherapy. Sex modulation of immunotherapy benefit, however, has not yet been explored using patient-level data, where potential confounders, as well as histologic type, can be accounted for. Here we investigated the association between sex and chemoimmunotherapy efficacy for non-small cell lung cancer (NSCLC) using a large, nation-wide dataset. Patients & methods Stage IV NSCLC patients diagnosed in 2015 were identified in the National Cancer Database (NCDB). Patients were treated with either chemoimmunotherapy or chemotherapy alone. The efficacy of the addition of immunotherapy treatment by sex was investigated using both an adjusted Cox proportional hazards model and propensity-score matching, in both the overall cohort and stratified by histological subtype. Results 2064 (16%) patients received chemoimmunotherapy and10,733 (84%) received chemotherapy alone. Adjusted survival analysis in the overall cohort showed that both males (hazards ratio (HR) adj : 0.80, 95% CI: 0.74–0.87) and females (HR adj : 0.83, 95% CI: 0.76–0.90) had better OS when treated with chemoimmunotherapy than chemotherapy alone, with no statistically significant interaction between sex and receipt of immunotherapy ( p  = 0.63). Propensity matching confirmed these results. However, for those with squamous cell histology, male patients derived more benefit from chemoimmunotherapy treatment than females (HR adj : 0.73, 95% CI: 0.58–0.91 vs HR adj : 1.03, 95% CI: 0.76–1.38; p for interaction = 0.07). Conclusion Male patients with squamous cell carcinoma may derive more benefit from chemoimmunotherapy treatment. Histology likely plays an important role in how sex modulates immunotherapy efficacy.

Lung cancer screening with low-dose computed tomography has been shown to significantly reduce lung cancer–related mortality in high-risk patients. However, patients diagnosed with lung cancer are typically older and often have multiple age- and smoking-related comorbidities. As a result, cancer screening in older adults remains a complex decision, requiring careful consideration of patients' risk characteristics and life expectancy to ensure that the benefits outweigh the risks of screening. In this review, we evaluate the evidence regarding lung cancer screening, with a focus on older patients. PubMed was searched to identify relevant studies evaluating the clinical outcomes of lung cancer screening. The key words used in our search included non–small cell lung cancer (NSCLC), screening, older, comorbidities, computed tomography, and survival. While we primarily looked for articles specific to older patients, we also focused on subgroup analysis in older patients in larger studies. Finally, we reviewed all relevant guidelines regarding lung cancer screening. Guidelines recommend that lung cancer screening be considered in adults aged 55 to 80 years who are at high risk based on smoking history (ie, 30-pack–year smoking history; having smoked within the past 15 years). Patients who fit these criteria have been shown to have a 20% reduction in lung cancer–related mortality with the use of low-dose computed tomography versus chest radiography. High rates of false-positive results and potential overdiagnoses were also observed. Therefore, screening is generally not recommended in adults with severe comorbidities or short life expectancy, who may experience limited benefit and higher risks with screening. However, several studies have shown a benefit with continued lung cancer screening with appropriate selection of older individuals at the highest risk and with the lowest comorbidities. Older patients experience the highest risk for lung cancer incidence and mortality, and stand to be the most likely to benefit from lung cancer screening. However, careful consideration must be given to higher rates of false-positives and overdiagnosis in this population, as well as tolerability of surgery and competing risks for death from other causes. The appropriate selection of older individuals for lung cancer screening can be greatly optimized by using validated risk-based targeting.

Background Immune checkpoint inhibitors targeting the programmed cell death protein‐1 (PD‐1) and programmed death ligand‐1 (PD‐L1) axis (collectively referred to as PD[L]1i) have demonstrated clinical benefits in non‐small cell lung cancer (NSCLC) patients. The purpose of this United States‐based real‐world study is to examine changes in the landscape of first‐line therapies for NSCLC since the introduction of PD(L)1i. Methods Patients with NSCLC initiating first‐line treatment between May 1, 2017, and October 31, 2020, were identified in the IBM MarketScan® database. Patients were assigned groups based on first‐line therapy: PD(L)1i monotherapy, chemotherapy alone, PD(L)1i with chemotherapy, or targeted therapy for patients with actionable driver mutations. Results A total of 5431 patients with NSCLC starting first‐line treatment were identified: chemotherapy alone 2568 (47%), PD(L)1i with chemotherapy 1364 (25%), PD(L)1i monotherapy 790 (15%), and targeted therapy 709 (13%). The use of PD(L)1i monotherapy and targeted therapy remained consistent, while the percentage of patients receiving PD(L)1i with chemotherapy more than doubled. Over a third of patients in 2019 and 2020 received chemotherapy alone. Patients aged ≥65 years (odds ratio [OR]: 0.80; 95% confidence interval [CI]: 0.68–0.95), females (OR: 0.86; 95% CI: 0.74–0.98), and those with respiratory (OR: 0.82; 95% CI: 0.71–0.94) or kidney (OR: 0.56; 95% CI: 0.40–0.77) disease were less likely to have received PD(L)1i with chemotherapy than patients that received chemotherapy alone. Conclusions Since the approval of PD(L)1i for NSCLC, their use has significantly increased for first‐line treatment, especially when used in combination with chemotherapy. A significant proportion of patients received chemotherapy alone. Since the approval of PD(L)1i for NSCLC, their use has significantly increased for first‐line treatment, especially when used in combination with chemotherapy. A significant proportion of patients received chemotherapy alone.

BackgroundCancer vaccines aim to generate antigen-specific CD8+ T cell responses but efficacy has been hampered by inefficient targeting of antigens to antigen presenting cells (APCs) for presentation on MHC-I. Cell Squeeze® technology delivers target antigens directly into red blood cells (RBCs) using temporary cell membrane disruption via a microfluidic chip. During the Cell Squeeze® process, phosphatidylserine is flipped to the extracellular membrane, making the RBCs appear aged. TLR3 agonist, poly I:C, is also delivered into RBCs, which serves to mature target APCs and ensure that presentation of tumor antigens occurs in an immunostimulatory context. The resultant SQZ® activating antigen carriers (AACs) thus leverage the natural clearance mechanism of aged RBCs, via phagocytosis by professional APCs, to enhance presentation of antigens on MHC-I of endogenous APCs. SQZ-AAC-HPV is an autologous RBC cell cancer vaccine targeting HPV16 viral oncoproteins E6 and E7 using the Cell Squeeze® technology.MethodsSQZ-AAC-HPV-101 (NCT04892043) enrolled HLA-A*02+patients with advanced HPV16+ cancers who had progressed after standard therapy, have an ECOG of 0–1, proper organ function, and measurable lesion(s). After whole blood collection, the cell product is manufactured in less than 24 hours with a collection-to-release time of ~1 week. SQZ-AAC-HPV was given IV q3w without a conditioning regimen. The response was assessed via RECIST 1.1 and biopsies were required at baseline and day 28 for pharmacodynamic biomarker analysis.ResultsFive patients [head and neck (4), anorectal (1)] were dosed in 2 monotherapy cohorts (from 0.5 to 5.0 x10e8/kg [DP]). There were no DLTs, no Grade (G) >2 related SAEs and no related G >3 AEs. One patient in the high dose cohort died due to disease progression in cycle one. Four of the five patients remain on SQZ-AAC-HPV treatment. Three patients in the low dose cohort have undergone at least one on-treatment scan; two patients showed a best overall response of stable disease with the third patient demonstrating a confirmed complete response of their anorectal cancer. Notably all three of these patients were immune checkpoint inhibitor naïve. Paired biopsy analysis for the patient with a confirmed complete response revealed an increase in CD8 density by IHC and a post-treatment tumor microenvironment with a high density of CD8 T cells and a low density of regulatory T cells per MIBI analysis.ConclusionsSQZ-AAC-HPV treatment was generally well-tolerated and initial efficacy data are encouraging. This presentation may include safety, additional efficacy, and biomarker data from a cut-off proximal to the presentation.AcknowledgementsWe thank the patients, their families, and their caregivers for their time and their willingness to participate in this study. We also thank the investigators and the investigational site staff for their contributions to the study.Ethics ApprovalThe study was performed in accordance with ethical principles that originated in the Declaration of Helsinki consistent with the ICH/GCP and applicable regulatory requirements. The protocol was approved by IRBs/IECs at each center. Patients provided written informed consent to participate.

Survival after multiple myeloma has improved with the use of immunomodulatory drugs--thalidomide, lenalidomide, and pomalidomide. Pomalidomide, the latest immunomodulatory drug to be approved by the US Food and Drug Administration, was developed by modifying thalidomide's chemical structure to increase potency and improve safety. Pomalidomide undergoes extensive cytochrome P450-mediated metabolism and has a toxicity profile mainly characterised by myelosuppression. Here, we discuss the first case of pomalidomide-induced hepatotoxicity reported under post-marketing surveillance.