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The article provides information on common clinical situations encountered by oncologists caring for patients with advanced non-small cell lung cancer (NSCLC). Topics discussed include how to approach a newly diagnosed patient with metastatic NSCLC who has high PD-L1 expression but their molecular profile is pending, how to manage patients who have progressed on chemotherapy regardless of line of therapy, and what they recommend to a newly diagnosed patient with EGFR-positive metastatic NSCLC.

The increasing incidence of lung cancer diagnosis during pregnancy has brought new challenges and opportunities to expand the knowledge gap in this protected patient population. Here, available data and top recommendations for the practicing oncologist are discussed. [ABSTRACT FROM AUTHOR]

PURPOSE: KRAS is the most commonly mutated driver oncogene in non–small cell lung cancer (NSCLC). Sotorasib and adagrasib, KRASG12C inhibitors, have been granted accelerated US approval; however, hepatotoxicity is a common side effect with higher rates in patients treated with sotorasib proximal to checkpoint inhibitor (CPI) therapy. The aim of this study was to assess the feasibility and safety of adagrasib after discontinuation of sotorasib because of treatment-related grade 3 hepatotoxicity through real-world and clinical cases. METHODS: Medical records from five patients treated in real-world settings were retrospectively reviewed. Patients had locally advanced or metastatic KRAS G12C-mutated NSCLC and received adagrasib after sotorasib in the absence of extracranial disease progression. Additional data were collected for 12 patients with KRAS G12C-mutated NSCLC enrolled in a phase Ib cohort of the KRYSTAL-1 study and previously treated with sotorasib. The end points associated with both drugs included timing and severity of hepatotoxicity, best overall response, and duration of therapy. RESULTS: All patients were treated with CPIs followed by sotorasib (initiated 0-64 days after CPI). All five real-world patients experienced hepatotoxicity with sotorasib that led to treatment discontinuation, whereas none experienced treatment-related hepatotoxicity with subsequent adagrasib treatment. Three patients from KRYSTAL-1 transitioned from sotorasib to adagrasib because of hepatotoxicity; one experienced grade 3 ALT elevation on adagrasib that resolved with therapy interruption and dose reduction. CONCLUSION: Adagrasib may have a distinct hepatotoxicity profile from sotorasib and is more easily combined with CPIs either sequentially or concurrently. These differences may be used to inform clinical decisions regarding an initial KRASG12C inhibitor for patients who recently discontinued a CPI or experience hepatotoxicity on sotorasib. [ABSTRACT FROM AUTHOR]

Simple Summary: Precision immuno-oncology, the development of personalized treatments using the unique nature of an individual's DNA, immune cells, and their tumor's molecular profile, offers great promise. However, it has been well documented that biological sex considerably influences innate and adaptive immune responses, thereby conferring differences in the efficacy of lung cancer therapy between men and women. Despite this, women remain underrepresented in oncology clinical trials; this exclusion has resulted in our harboring of a limited understanding of the impact of immunotherapy on females and their survivorship, in addition to imprecise clinical recommendations. This review provides an overview of the sex-specific differences in immunity and immunotherapy efficacy, discusses contributing factors for the lack of women in clinical trials, and suggests future directions for precision oncology research, to ultimately aid in the development of treatment guidelines and recommendations that wholly consider the unique impact of immunotherapy on females and the intersectionality among them. Precision immuno-oncology involves the development of personalized cancer treatments that are influenced by the unique nature of an individual's DNA, immune cells, and their tumor's molecular characterization. Biological sex influences immunity; females typically mount stronger innate and adaptive immune responses than males. Though more research is warranted, we continue to observe an enhanced benefit for females with lung cancer when treated with combination chemoimmunotherapy in contrast to the preferred approach of utilizing immunotherapy alone in men. Despite the observed sex differences in response to treatments, women remain underrepresented in oncology clinical trials, largely as a result of gender-biased misconceptions. Such exclusion has resulted in the development of less efficacious treatment guidelines and clinical recommendations and has created a knowledge gap in regard to immunotherapy-related survivorship issues such as fertility. To develop a more precise approach to care and overcome the exclusion of women from clinical trials, flexible trial schedules, multilingual communication strategies, financial, and transportation assistance for participants should be adopted. The impact of intersectionality and other determinants of health that affect the diagnosis, treatment, and outcomes in women must also be considered in order to develop a comprehensive understanding of the unique impact of immunotherapy in all women with lung cancer. [ABSTRACT FROM AUTHOR]

Background: Sexual health is understudied and underreported in patients with lung cancer, and most data precede the approval of widely used targeted therapies and immune checkpoint inhibitors. The authors sought to evaluate the prevalence of sexual dysfunction in women with lung cancer in our current clinical environment. Methods: This cross‐sectional survey study was administered online to 249 women via the GO2 for Lung Cancer (GO2) Registry, using the Patient‐Reported Outcomes Measurement Information System Sexual Function and Satisfaction Measures questionnaire. Participants were recruited between June 2020 to June 2021. Eligibility criteria included age >18 years, self‐identifying as a woman, fluency in English, and a lung cancer diagnosis within 10 years. Results: Most (67%) had stage IV lung cancer and 47% were receiving targeted therapy; 66% were undergoing active treatment. Despite 54% of participants reporting "recent" sexual activity, most (77%) indicated having little to no interest in sexual activity and 48% reported recent minimal satisfaction with their sex life. The most common reasons negatively affecting participants' satisfaction with their sex life included fatigue (40%) and feeling sad/unhappy (28%). Common reasons for lack of recent sexual activity included lack of interest (68%) and vaginal dryness or pain (30%). Compared to pre‐diagnosis, women were significantly less likely to have recent interest in sexual activity. In multivariable logistic‐regression, vaginal dryness showed a significant negative association with recent interest in sexual activity. Conclusions: Sexual dysfunction is prevalent in women with lung cancer. Sexual health should be integrated into routine care for patients with lung cancer. Most women with a lung cancer diagnosis in the past 10 years reported having little to no interest in sexual activity and recent minimal satisfaction with their sex life. Common reasons for lack of recent sexual activity included lack of interest and vaginal dryness or pain. [ABSTRACT FROM AUTHOR]