Autoimmune encephalitis in a woman with lung adenocarcinoma undergoing treatment with an immune checkpoint inhibitor (Pembrolizumab). What was the trigger: The neoplasm or the treatment?

Introduction: In a major paradigm shift of management of high-risk early-stage triple negative breast cancer (TNBC), the KEYNOTE-522 trial showed evidence to suggest that the addition of the immune checkpoint inhibitor (ICI) pembrolizumab to current standard-of-care chemotherapy leads to greater clinical efficacy than that of chemotherapy alone. However, the addition of an ICI carries with it the risk of immunotherapy-related cardiotoxicities. This raises concern for additive risks for cardiotoxicity for patients with high-risk early-stage TNBC receiving both anthracycline and ICI. Hypothesis: Management of high-risk early-stage TNBC with a treatment regimen consisting of anthracycline and ICI will have no increase in cardiotoxicity when compared to those receiving anthracycline alone. Aims: The purpose of this study is to identify if the combination of anthracycline and ICI in the management of high-risk early-stage TNBC is associated with greater cardiotoxicity than that of those on anthracycline alone. Methods: Patients with TNBC were identified within the electronic health record system at our institution. Cohorts were created based on management strategy: anthracycline with ICI and anthracycline without ICI. Patient demographics, comorbidities, functional status, medications, cardiac imaging, management, and outcomes were analyzed retrospectively. Cohorts were then compared for analysis of time to adverse cardiac event. An alpha value of 0.05 was used to determine statistical significance. Results: A total of 385 patients with TNBC were included in the study, with 312 receiving anthracycline without ICI and 73 receiving anthracycline with ICI. Baseline characteristics between the two cohorts were well balanced with no significant differences in prevalence of comorbidities. There were no significant differences in incidence of general cardiac events, heart failure, acute coronary syndrome, cardiac arrhythmias, and pericardial effusion between these two cohorts following each respective treatment regimen. Furthermore, there was no significant difference in time to cardiac events between the two groups. Conclusion: There appears to be no significant differences in cardiac events between patients with TNBC on anthracycline with ICI and those on anthracycline without ICI. Given no significant differences in cardiotoxicity, these findings further favor use of an ICI in management of high-risk early-stage TNBC and serve to reduce clinician hesitancy.

Simple SummaryAdjuvant treatment with the immune checkpoint inhibitors (ICI) pembrolizumab or nivolumab, or the targeted therapies dabrafenib and trametinib is recommended for patients with completely resected stage III melanoma and significantly decreases recurrence risk. Currently, limited data are available on physicians’ prescription preferences regarding ICI and targeted therapies and patient outcome in clinical practice. This study investigates the real-world situation of 109 patients from the Cancer Center of the University Hospital Bern, Switzerland, with an indication for adjuvant treatment since 2018. We describe treatment patterns, recurrence, and toxicity rates under immune checkpoint inhibitors, and targeted therapies.Approved adjuvant treatment options for stage III melanoma are the immune checkpoint inhibitors (ICI) pembrolizumab and nivolumab, and in presence of a BRAF V600E/K mutation additionally dabrafenib in combination with trametinib (BRAFi/MEKi). This study aims to describe prescription patterns and recurrence and toxicity rates of adjuvant-treated melanoma patients from the Cancer Center of the University Hospital Bern, Switzerland. One hundred and nine patients with an indication for adjuvant treatment were identified. Five (4.6%) had contraindications and, as such, were not proposed any adjuvant treatment, while 10 patients (9.2%) declined treatment. BRAF status was known for 91 (83.5%) patients. Of 40 (36.7%) patients with BRAF V600E/K melanoma, pembrolizumab was prescribed to 18 (45.0%), nivolumab to 16 (40.0%), and dabrafenib/trametinib to three (7.5%) patients. Grade 3–4 toxicity was reported in 18.9% and 16.7% of all the patients treated with pembrolizumab and nivolumab, respectively. No toxicities were observed for dabrafenib/trametinib. Thirty-eight percent of the patients treated with pembrolizumab and 40.0% of those treated with nivolumab relapsed. No relapses were reported for dabrafenib/trametinib. Prescription patterns indicate a clear preference for adjuvant ICI treatment.

Immune checkpoint inhibitors (ICIs) are being used in patients with various advanced malignancies, and patient outcomes have improved considerably. Although ICIs can effectively treat tumors, 30–60% of patients experience immune-related adverse events (irAEs). Autoimmune encephalitis (AE) is a rare irAE that has become a novel topic in neuroimmunology and has received increasing attention in recent years. Herein, we report a rare case of GAD65-antibody–associated AE after metastatic small cell lung cancer treatment with pembrolizumab. The patient received IVIg therapy for AE and continuous pembrolizumab therapy without suspension of tumor treatment. At 1 year follow-up, both the patient’s AE symptoms and tumors were stable. We consider that the treatment of ICI-associated AE should be more individualized with prudent decision-making and should balance the tumor progression and AE treatment. In addition, we have also comprehensively reviewed the literature of ICI-associated AE, and summarized the clinical features, treatment, and prognosis of AE caused by ICI, thus broadening our understanding of the neurological complications caused by ICI.

Introduction: the use of immunotherapy agents in combination with chemotherapy has shown its effectiveness in randomized trials for the first-line treatment of metastatic gastric cancer. The paper considers the experience of the Moscow oncological service in evaluating the effectiveness of pembrolizumab and nivolumab in patients with metastatic gastric cancer, depending on morphological (CPS, MSI) characteristics.Aim of the study: to compare progression-free survival (PFS) and overall survival (OS) in patients with advanced gastric cancer who underwent immunotherapy (as monotherapy or in combination with chemotherapy) or standard chemotherapy with oxaliplatin and fluoropyrimidines.Patients and methods: 194 patients met the inclusion criteria. Of these, 52 patients received checkpoint inhibitors (ICI) (18-immunotherapy alone; 31-in combination with chemotherapy, 15 patients received pembrolizumab and 37 patients received nivolumab); 142 patients received chemotherapy CAPOX or FOLFOX without ICI. The median follow-up was 29.5 months (17.4–62 months). Males were 55.8 % and 57.7 % with average age of 64.5 and 65.9 years, ECOG 2 was detected in 15.4 % and 8.5 % of patients. Other characteristics were also comparable: CPS > 10 69.2 % and 19.7 % (p = 0.0001), MSI 26.2 % and 4.9 % (p = 0.009), 2nd lines and further treatment were received by 36.5 % and 69.3 % (p = 0.0001), respectively.Results: in the entire population PFS was 7.9 months and 6.4 months (HR 0.46; 95 % CI 0.32–0.67, p = 0.0001), and OS was 17.3 months and 14.6 months (HR 0.71; 95 % CI 0.49–1.04, p = 0.076), respectively. The univariate analysis showed that only 1 prognostic factor for survival — the number of organs with metastases. In accordance with this, in case of the presence of metastases in 1–2 organs the use of ICI had an advantage in terms of PFS (p = 0.051 and p = 0.001), while in case of 3 or more organs involved there was no advantage (p = 0.62). Assessing the effect of the CPS level in patients with MSS phenotype, it was shown that at CPS0–9 there was no advantage in PFS (6.1 months and 6.9 months, p = 0.7) and OS (8.8 months and 14.9 months, p = 0.39). With CPS > 10, an advantage was noted when adding ICI for PFS (9.9 months and 4.4 months, p = 0.0001), and OS 18.2 months and 12.1 months (p = 0.23). However, the results did not differ at the CPS level > 50. When evaluating patients with MSI, we demonstrated that with a median PFS of 6.6 months and 5.2 months, respectively (HR 0.48; 95 % CI 0.17–1.4; p = 0.165), the median OS in patients who received ICI with or without CT was significantly higher — 24.3 months and 11.1 months, respectively (HR 0.4; 95 % CI 0.13–1.21; p = 0.11).Conclusions: the use of ICI in the first line therapy for metastatic gastric cancer (compared with CT alone) increases the proportion of patients living without progression for 12 months or more, and the overall survival rate was also increased by more than 2 times. The threshold level of CPS for ICI assignment needs to be > 10. The relationship between the effectiveness of immunotherapy and PD-L1 expression in gastric cancer with MSI tumors requires further study in a larger sample of patients. Information at the CPS level, the presence of MSI and HER2 / neu should be presented at the time of discussion of treatment tactics at the onset of metastatic disease.

Window of opportunity trials with immune checkpoint inhibitors in triple-negative breast cancer

We present the case of 72-year-old male with metastatic de-differentiated chondrosarcoma ("DDCS"). DDCS is a rare soft tissue cancer that carries a dismal prognosis in the metastatic stage, and is resistant to both traditional chemotherapy and radiotherapy. There is a distinct lack of proven systemic therapies. This case report is distinguished in that our patient had a significant clinical response to combination therapy with an immune checkpoint inhibitor (Pembrolizumab) and a multi-targeted tyrosine kinase inhibitor (Pazopanib). Our patient presented with bony pain after suffering a pathological fracture of the left humerus after grabbing a fence. He did not report prior constitutional symptoms or bony pain. On examination he was clinically in atrial fibrillation and reported reduced exercise tolerance with a New York Heart association grading of 2. There were no other pertinent clinical findings. FDG PET-CT scan revealed a 10cmx5cm destructive intra-osseous lesion of the proximal humerus, markedly FDG-avid, without evidence of metastatic disease. He underwent immediate surgical resection, followed by adjuvant radiotherapy to the left humerus. Tumour histology revealed a high-grade DDCS. Genetic sequencing revealed alterations in IDH2, PTCH1 and TERT promoter. Restaging FDG PET scan 3 months after diagnosis revealed lung metastases. The patient was commenced on Vismodegib with best disease response of progressive disease. Eight months after diagnosis he was commenced on combination therapy of Pazopanib and Pembrolizumab, with significant reduction in size of lung metastases. He sustained a progression free period of 6 months on this regime. Treatment course was complicated primarily by hepatotoxicity, which resolved with dose reduction of Pazopanib. Eleven months after diagnosis, FDG PET-CT revealed relapse and significant progression of metastatic disease and systemic therapy was ceased. The patient passed away 14 months after diagnosis. This case report is a valuable example of promising emerging systemic therapies for advanced DDCS, where the present standard of care lacks a repertoire of effective therapies.

Immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (NAEs) are rare but serious side effects, of which autoimmune encephalitis (AIE) is a potentially fatal central nervous system disorder requiring more attention. We performed a retrospective disproportionality analysis of NAE reports in the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Event Reporting Database (JADER) from 2004 to 2024, utilizing reporting odds ratio (ROR), proportional reporting ratio (PRR), the Bayesian confidence propagation neural network BCPNN, and the multi-item gamma Poisson shrinker (MGPS) for signal detection. In total, 3,999 reports of ICI-associated NAEs were identified from the FAERS database, of which 1,998 reports were AIE. 1,558,251 reports of AEs were collected from the JADER database, which contained 890 AIE reports. ICIs, including pembrolizumab, nivolumab, atezolizumab, ipilimumab, and durvalumab, were identified among the top 30 agents in both databases, demonstrating significant signals across all 4 algorithms. Except for noninfectious myelitis, acute disseminated encephalomyelitis, and multiple sclerosis, positive signals were detected in all other preferred terms (PTs). These NAEs accounted for 23.7% of total mortality, with myasthenia gravis (MG) exhibiting the highest mortality rate at 30.63%. Specific PTs, such as aseptic meningitis, AIE, chronic inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome, MG, myelitis, and immune-related myopathy, were associated with the severity of outcomes, showing significant statistical differences between severe and non-severe cases (p < 0.05). Our study found a notable correlation between ICIs and AIE and other specific NAEs, highlighting the demographic characteristics, time to onset, and disease severity of ICI-induced NAEs, thereby facilitating the timely recognition and treatment of these ICI therapy-related complications.

Immunotherapy using immune checkpoint inhibitors (ICIs) has demonstrated efficacy in treating a wide range of oncological diseases, but the use of this group of drugs is associated with the risk of developing serious immune-related adverse events (irAEs). Although relatively rare, neurological complications associated with ICI use are often life-threatening. The most common of these include myositis, myasthenia (with or with-out myositis), peripheral neuropathies, including Guillain–Barre syndrome, autoimmune encephalitis, myelitis, and demyelinating syndromes. This article presents five clinical observations of the development of neurological complications against the background of the use of anti-PD-1 inhibitors (pembrolizumab, nivolumab) as monotherapy or in combination with an anti-CTLA-4 inhibitor (ipilimumab). The cases presented were diagnosed with transverse myelitis, peripheral neuropathies meeting the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy, and myositis, including in combination with myasthenia gravis. To relieve these conditions, glucocorticoids were used in the form of pulse therapy followed by oral administration, high-volume plasmapheresis, and cytostatic drugs. The treatment provided resulted in marked clinical improvement. The observations presented emphasise the importance of early diagnosis and effective treatment of irAEs as well as a multidisciplinary approach to the management of such patients. To date, the problems of selecting the optimal management strategy for irAEs and assessing the safety of subsequent ICIs use remain relevant and require further prospective studies. In addition to demonstrating the importance of a multidisciplinary approach, the purpose of presenting these observations is to raise awareness among neurologists about neurological immune-related adverse events caused by ICI therapy. The relevance of this task is determined by the fact that the widespread introduction of ICI into clinical practice for the treatment of various malignant neoplasms will inevitably lead to an increase in such cases in neurological practice, which predetermines the need for neurologists to be prepared to diagnose and manage such patients.

Introduction:Aging is the biggest cancer risk, and immune checkpoint (IC) inhibition (ICI) is a revolutionary cancer immunotherapy approach. Nonetheless, there are limited preclinical/clinical data regarding aging effects on ICI outcomes or age effects on IC expression in different organs or tumors.Methods:Flow cytometry assessed IC on immune and non-immune cells in various organs in young and aged BL6 mice. Comparisons: aged versus young naïve WT versus interferon-γKO mice and WT challenged with B16F10 melanoma and treated with αPD-1 or αPD-L1 ICI. We co-cultured young and aged T cells and myeloid cells in vitro and used OMIQ analyses to test cell–cell interactions.Results:αPD-1 ICI treated melanoma in young and aged hosts, whereas αPD-L1 ICI was only effective in young. We found considerable, previously undescribed age effects on expression of various IC molecules participating in the ICI treatment, including PD-1, PD-L1, PD-L2, and CD80, in distinct organs and in the tumor. These data help explain differential ICI efficacy in young and aged hosts. Host interferon-γ influenced age effects on IC expression in both directions depending on specific IC molecule and tissue. IC expression was further affected by tumor challenge on immune, non-immune, and tumor cells in tumor and other organs. In in vitro co-culture, αPD-1 versus αPD-L1 distinctly influenced polyclonal T cells in young versus aged, suggesting mechanisms for distinct age-related ICI outcomes.Conclusion:Age affects IC expression on specific immune cells in an organ- and tissue-specific manner. ICs were generally higher on aged immune cells. High immune-cell PD-1 could help explain αPD-1 efficacy in aged. High co-expression of CD80 with PD-L1 on dendritic cells could help explain lack of αPD-L1 efficacy in aged hosts. Factors other than myeloid cells and interferon-γ also affect age-related IC expression and T cell function, meriting additional studies.

Simple SummaryAntibody–drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) are two promising therapeutic modalities against many types of cancers. However, many patients develop resistance. The resistance mechanisms to ADCs and ICIs have been comprehensively illuminated in this review. A combination of ADCs and ICIs has been explored to overcome resistance to ADC or ICI single treatment. Recently, a clinical study demonstrated that a combination of enfortumab vedotin (EV), an ADC against Nectin-4, with the ICI pembrolizumab achieves remarkable clinical efficacy as the first-line therapy for the treatment of locally advanced or metastatic urothelial carcinoma. The underlying mechanism is likely due to the enhancement of pembrolizumab-induced anticancer immunity mediated by EV. With the emerging use of combination therapy strategy, it is critical to understand the mechanism of successful and/or failed clinical studies for the future development of combination therapy of ADCs with ICIs.Antibody–drug conjugates (ADCs) consist of an antibody backbone that recognizes and binds to a target antigen expressed on tumor cells and a small molecule chemotherapy payload that is conjugated to the antibody via a linker. ADCs are one of the most promising therapeutic modalities for the treatment of various cancers. However, many patients have developed resistance to this form of therapy. Extensive efforts have been dedicated to identifying an effective combination of ADCs with other types of anticancer therapies to potentially overcome this resistance. A recent clinical study demonstrated that a combination of the ADC enfortumab vedotin (EV) with the immune checkpoint inhibitor (ICI) pembrolizumab can achieve remarkable clinical efficacy as the first-line therapy for the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC)—leading to the first approval of a combination therapy of an ADC with an ICI for the treatment of cancer patients. In this review, we highlight knowledge and understanding gained from the successful development of EV and the combination therapy of EV with ICI for the treatment of la/mUC. Using urothelial carcinoma as an example, we will focus on dissecting the underlying mechanisms necessary for the development of this type of combination therapy for a variety of cancers.

466P - Cancer immunotherapy efficacy and patients’ age: A systematic review and meta-analysis

Background: Immune checkpoint inhibitors have changed the therapeutic milieu for patients with metastatic melanoma. However, their use may promote autoimmunity in virtually any organ in the body due to the blockade of intrinsic immune down regulators such as cytotoxic T-lymphocyte antigen- 4 (CTLA-4), programmed cell death 1 (PD1) or its ligand (PDL1). Immune mediated adverse neurological events are rare with these agents, however, and are seen in &lt; 1% of treated patients. We report a patient with immune checkpoint inhibitor associated autoimmune encephalitis, with complete clinical recovery after treatment.Case Report: A 49-year-old female with metastatic melanoma currently on nivolumab therapy but recently on ipilimumab/nivolumab combined therapy presented with a new headache. She also reported associated confusion, loss of balance, personality changes and language difficulty. Magnetic resonance imaging of the brain did not reveal any evidence of metastasis, infarct, meningitis, or encephalitis. Lumbar puncture revealed an elevated protein level and pleocytosis, with a normal glucose level. She was started on empiric glucocorticoid therapy with a presumptive diagnosis of immune checkpoint inhibitor associated autoimmune encephalitis. She improved considerably by day 3 of treatment with complete resolution of neurological symptoms by day 5.Conclusion: Immune checkpoint inhibitors are increasingly important in cancer immunotherapy as they can cause sustained remissions in patients with metastatic melanoma and other malignancies. Because these drugs block immune-regulatory targets, they can lead to enhanced activation of immune system resulting in immune-related adverse events. Autoimmune encephalitis is a rare immune-related adverse event associated with immune checkpoint inhibitors. The incidence of autoimmune encephalitis is higher with combination or sequential CTLA-4 (ipilimumab) and PD1(nivolumab) inhibitor therapy than with monotherapy. With more widespread use of immunotherapy, it is important for clinicians to be aware of this rare and reversible cause of encephalitis. Early recognition and prompt initiation of immunosuppressive therapy with glucocorticoids is essential to enhance neurological recovery.

Colorectal cancer is a prevalent malignancy that necessitates personalized chemotherapy, especially with the advent of molecular-targeted drugs and immune checkpoint inhibitors. In Japan, immune checkpoint inhibitors have been approved for unresectable advanced and recurrent colorectal cancer; however, their use in preoperative therapy for colorectal cancer has not yet been approved. Globally, neoadjuvant immunotherapy has demonstrated promising outcomes in colorectal cancer cases with high immunogenicity, including microsatellite instability-high and deficient mismatch repair. We report a case of a microsatellite instability-high, clinically unresectable, locally advanced ascending colon cancer treated with immune checkpoint inhibitors, which showed significant tumor shrinkage, facilitating standard surgery while avoiding adjunct organ resection. The patient, a 70-year-old male, experienced chronic abdominal pain and diarrhea. Lower gastrointestinal endoscopy and computed tomography confirmed a diagnosis of ascending colon cancer with suspected invasion into the descending duodenum. Although curative resection was technically feasible with pancreatoduodenectomy, neoadjuvant chemotherapy was selected to reduce tumor size, considering the patient's overall condition. Companion diagnostics revealed microsatellite instability-high status and BRAF V600E mutation, leading to the initiation of chemotherapy combined with an immune checkpoint inhibitor (pembrolizumab). Subsequently, prolonged pembrolizumab administration was challenging due to suspected immune-related adverse events, including diarrhea and pruritus. However, significant tumor reduction was observed during a follow-up computed tomography scan, facilitating surgery approximately 6 months after treatment initiation. The perioperative period was uneventful, and the patient was discharged on the eighth day after operation. The final pathological results revealed complete tumor disappearance (histological effect of chemotherapy: Grade 3). This case highlights the potential of neoadjuvant immunotherapy in reducing surgical invasiveness in patients with colorectal cancer.

Immune checkpoint inhibitors (ICI) cemiplimab and pembrolizumab have revolutionized the treatment of advanced cutaneous squamous cell carcinoma (cSCC). We aimed to evaluate the effectiveness and safety of ICI in a real-world cSCC population, including patients with conditions that would exclude clinical trial participation. In this single-center, retrospective cohort study, we included all non-trial patients with advanced cSCC treated with ICI between 2017 and 2022. We evaluated investigator-assessed best overall response (BOR) and immune-related adverse events (irAEs). We correlated survival outcomes with age, performance status, immune status and irAEs. Of the 36 patients identified, the best overall response (BOR) to ICI was a partial response (PR) in 41.7%, a complete response (CR) in 27.8%, and stable disease in (SD) 13.9%. The progression-free survival (PFS) rate for 1 year was 58.1%; the median PFS was 21.3 months (95% CI 6.4-NE). The 1-year overall survival (OS) was 76.7%, and the median OS was 38.6 months (95% CI 25.4-NE). Immune-compromised patients, ECOG performance 2-3, and age ≥ 75 years were not significantly associated with PFS or OS. IrAE grades 3-4 were seen in 13.9% of patients. In our Canadian experience with real-world patients, ICI was an effective and safe treatment for advanced cSCC patients. Patients achieved great benefits with ICI regardless of age, immune status or ECOG performance status. We acknowledge the small sample size and retrospective methodology as the main limitations of our study.

e20125 Background: The addition of immunotherapy represents a significant breakthrough in the treatment paradigm of extensive-stage small cell lung cancer (ES-SCLC). Subgroup analyses highlight certain prognostic factors (i.e., performance status, cisplatin use, and the absence of brain metastases at diagnosis) associate with longer survival in SCLC. However, little is known related to clinical biomarkers to predict response to immunotherapy. Here, we inquire if certain SCLC-related variables may impact outcomes in this setting. Methods: We retrospectively reviewed charts of 149 patients diagnosed with SCLC treated at Indiana University Health and IU Simon Cancer Center from January 2018 to August 2024. Patients diagnosed with ES-SCLC who ever received immune checkpoint inhibitor (ICI) (durvalumab, atezolizumab, pembrolizumab, ipilimumab, and/or nivolumab) were included. Patients were divided into two groups based on progression-free survival (PFS) with ICI use: &lt;150 days (non-responders) and ≥150 days (responders). Univariate analysis was used to compare the demographics and pertinent malignancy- and therapy-related variables. Results: A total of 89 patients diagnosed with ES-SCLC with any ICI use were identified, with 57 patients (64%, non-responders) and 32 patients (36%, responders, Table 1). Multivariate analysis confirmed that a greater number of combined cycles ( P = .005) or the diagnosis of malignancy-related thromboembolism (VTE) (OR, 7.03; 95% CI, 0.99–49, P = .05) were associated with improved PFS. Univariate analysis revealed that responders received more combined chemotherapy plus ICI cycles (4 vs 3 cycles, P = .012). Syndrome of inappropriate antidiuretic hormone (SIADH), use of GCSF, or the presence of brain and/or liver metastases did not impact PFS with ICI use in SCLC. Similar maximum standard uptake values (max SUV) on baseline positron emission tomography (PET) scan were observed (16.5 vs. 14.7, P = .58). No difference in active tobacco use was observed between the groups. Conclusions: Many SCLC-related diagnoses failed to predict durable response to ICI. Patients who received 4 cycles of combined chemo-ICI for ES-SCLC had improved PFS, compared to those receiving fewer cycles. The diagnosis of malignancy-related VTE may be associated with improved PFS in this cohort. Additional understanding of clinical variables related to ICI response is needed. Patients’ characteristics by group. P -value Variable OverallN=89 Non-respondersN=57 RespondersN=32 Odds Ratio [95% Wald CI] History of VTE 8 (9%) 3 (5.3%) 5 (15.6%) 3.33 [0.741, 15] 0.117 ECOG PS 0 17 (25.4%) 10 (22.7%) 7 (30.4%) 2.28 [0.518, 9.989] 0.276 Presence of brain metastases 25 (28.1%) 17 (29.8%) 8 (25%) 0.78 [0.294, 2.092] 0.627 Cycles of concurrent chemo-ICI received 4 (3, 4) 3 (2, 4) 4 (3, 5) 1.58 [1.108, 2.245] 0.012 Current tobacco use 49 (55.1%) 31 (54.4%) 18 (56.3%) 1.35 [0.545, 3.362] 0.515