8525 Background: SHR-1826 is a novel ADC comprising a humanized IgG2 monoclonal antibody targeting c-MET, conjugated via a cleavable peptide-based linker to a topoisomerase I inhibitor payload. We conducted a multi-center, first-in-human, phase 1 trial of SHR-1826 in patients with advanced solid tumors. Here we report updated results, with a focus on patients with EGFR -mutated ( EGFRmut ) lung adenocarcinoma (LUAD). Methods: The study consisted of dose-escalation (i3+3 design), dose-expansion and efficacy-expansion phases. Patients with advanced solid tumors harboring MET alterations, who had failed standard therapy or had no available standard treatment options, were enrolled and received SHR-1826 intravenously at 2.2–6.0 mg/kg Q3W. In patients with EGFRmut LUAD, 4.0 and 5.0 mg/kg Q3W were evaluated during dose and efficacy expansion. Results: As of Dec. 3, 2025, 195 patients with lung (n=126), colorectal (n=40), gastric (n=22), liver (n=5), or pancreatic (n=2) cancer were treated. Median age was 59.0 yrs; 89.7% had ECOG performance status 1. Among 36 patients with EGFRmut LUAD, median number of prior lines of therapy was 2 (range 1–9); 97.2% had previously received EGFR-TKI (3 rd generation, 88.9%) and 75.0% received platinum-based chemotherapy. As of data cutoff, median follow-up was 14.4 months. Efficacy in EGFRmut LUAD across doses is shown in Table 1. Overall, the confirmed objective response rate (ORR) was 41.7% (95% CI 25.5–59.2) and median duration of response (DoR) was 14.1 months (95% CI 5.6–not reached [NR]). Median progression-free survival (PFS) was 9.8 mo (95% CI 5.8–15.4). Median overall survival (OS) was not reached; 12-month OS rate was 67.4% (95% CI 48.9–80.5). In all 195 patients, grade ≥3 treatment-related adverse events (TRAEs) were reported in 129 patients (66.2%), with all occurring in ≥5% being hematological toxicities. Interstitial lung disease occurred in 4 (3.1%; grade ≥3, n=2 [1.6%]) patients. TRAEs led to treatment discontinuation in 8 (4.1%) patients. No treatment-related deaths were reported. Conclusions: SHR-1826 demonstrated encouraging activity with manageable safety in heavily pretreated patients with MET-altered EGFRmut LUAD. Multiple trials are ongoing to assess SHR-1826 combined with other anti-tumor therapies in NSCLC. Clinical trial information: NCT06094556 . Efficacy outcomes in EGFRmut LUAD. 4.0 mg/kg (n=16) 5.0 mg/g (n=18) All patients (n=36) Confirmed ORR (n/N; 95% CI), % 31.3 (5/16; 11.0–58.7) 50.0 (9/18; 26.0–74.0) 41.7 (15/36; 25.5–59.2) DCR (n/N; 95% CI), % 87.5 (14/16; 61.7–98.4) 100.0 (18/18; 81.5–100.0) 94.4 (34/36; 81.3–99.3) Median DoR (95% CI), mo NR (8.6–NR) 9.7 (4.2–NR) 14.1 (5.6–NR) Median PFS (95% CI), mo 12.4 (2.6–NR) 8.4 (4.5–15.4) 9.8 (5.8–15.4) 12-mo OS (95% CI), % 67.0 (37.9–84.7) 69.1 (40.7–85.9) 67.4 (48.9–80.5) Data are based on the full analysis set. DCR, disease control rate.

Mefatinib, a novel second-generation epidermal growth factor (EGFR) tyrosine kinase inhibitor that has shown promising antitumor activity in targeting non-small cell lung cancer (NSCLC) with common and uncommon EGFR-activating mutations. In this phase III, randomized, double-blind trial in China, 336 eligible patients with advanced nonsquamous NSCLC harboring EGFR L858R or exon 19 deletion (ex19del) were assigned (2:1) to receive either mefatinib (60 mg daily, n = 223) or gefitinib (250 mg daily, n = 113). The primary endpoint was progression-free survival (PFS), assessed by an independent review committee (IRC). The trial is registered with chinadrugtrials.org.cn (CTR20192297). After a median follow-up of 15.9 months for mefatinib and 18.5 months for gefitinib, mefatinib demonstrated a significantly longer median IRC-assessed PFS compared to gefitinib (13.7 vs. 9.7 months; hazard ratio [HR] = 0.68; 95% confidence intervals [CI]: 0.53-0.87; p = 0.002). The 30-month overall survival rate was 60.2% for mefatinib and 54.3% for gefitinib. Patients with EGFR ex19del had comparable PFS for both treatment arms (p > 0.100), whereas patients with EGFR L858R had significantly longer median PFS when treated with mefatinib than gefitinib (13.7 vs 8.3 months HR = 0.55 [95% CI: 0.38-0.78]; p = 0.001). Patients with EGFR L858R had a 30-month overall survival rate of 56.6% with mefatinib and 43.7% with gefitinib. Treatment-related adverse events ≥grade 3 were reported in 45.7% of the mefatinib group and 24.8% of the gefitinib group. No new safety signals were observed for mefatinib. Mefatinib demonstrated superior efficacy to gefitinib with a similar tolerability profile in the first-line treatment of EGFR-mutated advanced NSCLC.

INTRODUCTION:Lung cancer remains a leading cause of cancer mortality globally, emphasising the critical need for non-invasive and cost-effective early screening methods. Breath analysis, detecting disease-specific volatile organic compounds (VOCs), presents a promising diagnostic avenue. METHODS:This cross-sectional study enrolled 4515 participants, including 4099 nonmalignant controls and 416 lung cancer patients. Exhaled breath samples were analysed using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF MS). Machine learning algorithms, particularly Light Gradient Boosting Machine (LGBM), were employed to construct classification models for distinguishing lung cancer from healthy controls and early-stage lung cancer from benign pulmonary nodules. Model interpretability was assessed using SHAP values. RESULTS:The LGBM model demonstrated superior performance, achieving 95% sensitivity, 98% specificity, and 98% accuracy for discriminating lung cancer from healthy controls. For the clinically challenging task of distinguishing early-stage lung cancer from benign nodules, LGBM achieved 97% sensitivity, 98% specificity, and 98% accuracy. SHAP analysis identified alpha-pinene (m/z 137) and methyl methacrylate (m/z 101) as the most significant VOCs. CONCLUSION:This large-scale study validates PTR-TOF MS based breath analysis combined with machine learning as a robust, non-invasive tool for early lung cancer detection. The LGBM model, supported by SHAP interpretability, offers high diagnostic accuracy in large cohorts. Future work will expand to diverse histological subtypes and multicenter validation. TRIAL REGISTRATION:ChiCTR2500101879.

Utilizing CAR-T cells to eliminate circulating tumor cells (CTCs) and inhibit metastasis is a promising strategy. However, this approach is hindered by the lack of specific antigens. Membrane-bound HSP70 (mHSP70) is commonly expressed on the cell membrane of numerous tumor types, notably on CTCs, making it an ideal target for CAR-T therapy to treat these malignancies and prevent metastasis. Here, we generated CAR T cells based on natural ligand granzyme B (GrB-CAR T) targeting mHSP70. GrB-CAR T cells exhibited potent cytotoxicity against a broad spectrum of cancer cell lines and stem-like cancer cells in vitro and effectively inhibited xenograft tumor growth in vivo. Importantly, CTCs maintain mHSP70 expression in xenograft models, and GrB-CAR T cells markedly decreased the number of CTCs, thereby preventing cancer metastasis. Moreover, despite human granzyme B exhibits cross-reactivity with mouse and macaque mHSP70—particularly given the complete homology between macaque and human mHSP70—no obvious adverse effects were observed in the animals treated with GrB-CAR T cells. These results demonstrate GrB-CAR T cells as a safe and effective approach with broad-spectrum anticancer activity and provide compelling experimental evidence for CAR T cell-mediated metastasis inhibition through targeting CTCs.

Mesenchymal-epithelial transition exon 14 skipping mutations (METex14) define a targetable molecular subset of non-small cell lung cancer (NSCLC), but optimal circulating tumor DNA (ctDNA) biomarkers to guide MET tyrosine kinase inhibitor therapy remain undefined. Within the EMBRACE trial of ensartinib, we conducted a prospective biomarker analysis with plasma collected at baseline (V0) and 4 weeks after treatment initiation (V1). ctDNA was profiled using a hybrid-capture next-generation sequencing panel covering 229 cancer-related genes, and mutations were classified into three monitoring paradigms: MET-specific alterations, canonical alterations (tier I/II), and pan-alterations (any variant in any gene on the panel). Baseline ctDNA positivity rates were 48.3%, 48.3%, and 75.9% for MET-specific, canonical, and pan-alterations, respectively, and declined across all categories at V1. Conversion to ctDNA negativity in any paradigm was associated with a tendency toward higher objective response rate (ORR) and longer progression-free survival (PFS). Moreover, clearance of MET-specific alterations conferred the greatest clinical benefit, with an ORR of 75.0% versus 16.7% and a median PFS of 9.3 months versus 2.2 months (p = 0.005). Among the three paradigms, MET-specific monitoring provided the most favorable diagnostic performance to identify long-term responders, with a specificity of 90% and a positive predictive value of 80%. These data demonstrate that early MET-specific ctDNA clearance is a robust on-treatment biomarker for ensartinib benefit in METex14 NSCLC, while broader ctDNA profiling remains valuable for uncovering emerging resistance mechanisms.

BRAF is the most frequently mutated protein kinase in human cancers, and in particular, the V600E mutation in the kinase domain confers a constitutively active conformation on the protein, thereby promoting oncogenesis. To date, several BRAF kinase inhibitors have been approved for treating cancer patients with the BRAF(V600E) mutation. However, the benefits of BRAF kinase inhibitors in clinical practice are limited, with an objective response rate of less than ∼50%. Therefore, novel diagnostic tools enabling the visualization of BRAF-mutant activity in an activity-based manner are quite desirable to determine BRAF-mutant status and guide treatment decisions for BRAF inhibitors. Here, we describe the design, synthesis, and application of a new fluorescence-enhanced probe HX50 by introducing an environment-sensitive fluorophore to the pharmacophore of BRAF inhibitors to visualize BRAF kinase activity in living cancer cells and tumor tissues (mouse models and human tumor biopsy samples). Interestingly, we found that the probe enables distinguishing the BRAF(V600E) mutation from the wild type not only in living cancer cells but also in xenograft mouse models. Furthermore, the fluorescence-enhanced probe was also able to visualize BRAF activity with high signal contrast in human tumors from lung cancer patients carrying the BRAF(V600E) mutation, but not BRAF wild-type. These results demonstrate that the strategically designed drug-based fluorescence-enhanced probe enables assessment of BRAF-mutant activity in tumor samples and holds promise as a useful diagnostic tool for predicting drug sensitivity and informing therapeutic strategy decisions for BRAF inhibitors.

Background: Following the 2021 first International Consensus on Severe Lung Cancer, global attention to patients with PS 2-4 has grown significantly. Recent advances in novel therapies, interventional techniques, and supportive care, along with emerging real world data, have expanded treatment opportunities for this population. To incorporate these advances, we have updated the consensus. Methods: A multidisciplinary panel comprising experts from oncology, radiation oncology, thoracic surgery, radiology, interventional medicine, respiratory medicine, critical care medicine, and nursing. After being presented with a comprehensive review of the current evidence pertaining to severe lung cancer and thorough discussions, the panel reached a consensus on 11 recommendations, each with over 70% expert agreement. Results: The 11 consensus points focused on definition and causes (n=2), assessment and general strategies (n=4), and specific treatment modalities (n=5) were updated or newly developed. This updated consensus emphasizes dynamic and precise detection, robust life support, flexible application of novel therapies, and MDT guided treatment adjustment based on PS dynamics. Early rehabilitation and comprehensive supportive care are integral to disease management. Conclusions: This consensus updates the definition, diagnostic evaluation, and treatment strategies, providing a practical framework for clinicians based on current evidence and multidisciplinary expert consensus. Prospective trials focusing specifically on patients with severe lung cancer are urgently needed.

IL‑6, a pleiotropic inflammatory cytokine predominantly secreted by fibroblasts, myeloid‑derived suppressor cells, tumor‑associated macrophages and tumor cells, is associated with poor prognosis of and therapeutic resistance in non‑small cell lung cancer (NSCLC). The activation of signaling pathways, including the JAK/STAT3, MAPK and PI3K/AKT pathways, promotes tumor survival. Furthermore, the IL‑6/JAK/STAT3 signaling axis has emerged as a key driver of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKI) resistance, orchestrating intricate crosstalk within the tumor microenvironment (TME) to promote cell survival and immunosuppression. The present review synthesized current evidence on the dual role of IL‑6 in mediating EGFR‑TKI resistance and blunting anti‑tumor immunity. The present review highlights the preclinical rationale for combining IL‑6 blockade with EGFR‑TKI or immune checkpoint inhibitors to overcome refractory disease. The present review also highlights the structure, molecular mechanisms and clinical insights of IL‑6 in the TME of EGFR‑mutant NSCLC and may provide optimized therapeutic strategies for EGFR‑TKI‑refractory NSCLC.

ABSTRACT The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a critical communication hub that translates extracellular signals into gene expression programs. Its aberrant activation serves as a central driver of tumorigenesis, metastasis, and immunosuppression in diverse malignancies. With research expanding from hematologic malignancies to solid tumors, the JAK/STAT pathway has gradually emerged as a promising therapeutic target for cancer treatment. This review systematically analyzes the multi‐dimensional dysregulation of the JAK/STAT pathway, encompassing somatic mutations, epigenetic modifications, and aberrant cytokine networks. We elucidate critical non‐canonical functions that underpin metabolic reprogramming and chromatin stability. Furthermore, we detail the pathway's pivotal role in bridging tumor cells with the microenvironment, focusing on myeloid‐derived suppressor cells (MDSC) recruitment and the reciprocal STAT3/PD‐L1 axis that fuels immune evasion and therapeutic resistance. Finally, we comprehensively evaluate the shifting therapeutic landscape, advocating for a transition from broad‐spectrum kinase inhibitors to high‐precision modalities such as allosteric modulators, proteolysis targeting chimeras (PROTACs), and novel combination strategies. By integrating the advance in the JAK/STAT pathway with cancer, this review underscores the potential of targeting this signaling axis for cancer therapy.

Cancer-associated fibroblast (CAF)-derived extracellular vesicles (EVs) mediate lung adenocarcinoma (LUAD) progression, but the role of their protein cargo remains poorly defined. Through quantitative proteomic profiling of EVs from patient-derived CAFs, we identify the V-ATPase subunit ATP6V1C1 as a protein highly enriched in pro-migratory CAF-EVs that critically mediates LUAD metastasis. Mechanistically, EV-delivered ATP6V1C1 suppresses insulin-like growth factor binding protein 3 (IGFBP3) expression by downregulating the transcriptional regulator ID1. This suppression of IGFBP3 induces epithelial-mesenchymal transition in LUAD cells and amplifies the oncogenic IGF1/IGF1R/Akt/ERK signaling cascade initiated by CAF-secreted IGF1. This dual action establishes a feedforward loop that exacerbates metastatic progression. Our findings identify ATP6V1C1 as a dual regulator of LUAD metastasis and suggest a potential stroma-targeted therapeutic approach.

ABSTRACT Intracranial efficacy of crizotinib and optimal postprogression therapies in c‐ros oncogene 1 (ROS1)‐positive non–small cell lung cancer(NSCLC) remain under‐explored. We performed a multicenter real‐world study across 17 Chinese hospitals (2015–2024) in 325 ROS1‐positive NSCLC patients to evaluate the intracranial efficacy of crizotinib and postprogression treatment strategies. Crizotinib achieved an overall response rate(ORR) of 78.5% and a median progression‐free survival (PFS) of 22.4 months. Patients with baseline brain metastases had a 66.7% intracranial response rate and a median central nervous system (CNS)‐PFS of 22.2 months, demonstrating intracranial benefit. After progression, next‐generation ROS1 inhibitors (active against the G2032R resistance mutation, for example, taletrectinib and repotrectinib) significantly prolonged PFS compared to older‐generation targeted agents (median 13.9 vs. 4.4 months), especially among patients with secondary ROS1 resistance mutations (ORR 66.7% vs. 14.3%). However, due to greater availability in China, earlier agents like lorlatinib and entrectinib were commonly used after crizotinib failure. In our cohort, lorlatinib demonstrated superior efficacy to entrectinib, with a trend toward longer PFS and higher overall (34% vs. 7%) and intracranial (50% vs. 0%) response rates. This large real‐world study confirms crizotinib's intracranial benefit and underscores the importance of next‐generation ROS1 inhibitors and older‐generation agents like lorlatinib—for improved patient outcomes after crizotinib resistance.

Epidermal growth factor receptor (EGFR) mutations are major oncogenic drivers in non-small cell lung cancer (NSCLC), occurring in 30–50

Pleural diseases is a common respiratory disorder, mainly characterized as pleural effusion and patients with pleural effusion caused by pneumonia and empyema constituted 29

BACKGROUND:This study investigated molecular testing, treatment patterns, and prognosis in Chinese patients who progressed from first-line (1 L), epidermal growth factor receptor -tyrosine kinase inhibitors (EGFR-TKIs) therapy, highlighting limited real-world data on clinical practice. METHODS:Consecutive eligible patients were prospectively enrolled in 16-centers in China. The primary endpoints were second-line (2 L) treatment patterns and clinical outcomes, including median progression-free survival (mPFS) and median overall survival (mOS) from 2 L treatment. RESULTS:Overall, 300 patients were enrolled in the study, and among them, 291 patients were included in the Full Analysis Set, and 213(73.2%) underwent molecular testing, after progression from 1 L therapy. 30.5% (65/213) had tissue samples, while 66.7% (142/213) had plasma samples. In tissue and plasma samples, T790M positive rates were 53.8% and 43.7%, respectively. mPFS and mOS for patients with T790M positive who received third generation (3 G) EGFR-TKIs as 2 L therapy were 14.7 months and 32.0 months, respectively. The mPFS for patients with T790M negative who received 3 G EGFR-TKIs, prior EGFR-TKIs plus local therapy, and chemotherapy as 2 L therapy were 7.6 months, 10.2 months, and 4.9 months, respectively. The corresponding mOS for these patients were 21.2 months, 16.6 months, and 15.0 months, respectively. No new safety signal emerged. CONCLUSIONS:Patients with acquired resistance to first generation (1 G)/second generation (2 G) EGFR-TKIs receiving 3 G EGFR-TKIs, especially T790M positive, showed better clinical outcomes after molecular testing. CLINICAL TRIAL REGISTRATION:The study has been registered at ClinicalTrials.gov (NCT04207775).

Background:The infection of Pneumocystis jirovecii pneumonia (PJP) increases the rate of malignancy-related death. It is crucial to estimate the risk of PJP in this population. Peripheral blood neutrophil-to-lymphocyte ratio (NLR) has been proven to have significant value in predicting bacterial infection. However, the associations between peripheral blood NLR and PJP in patients with solid tumors have not been investigated. We aimed to identify whether baseline peripheral-blood NLR was correlated with PJP in patients with solid tumors. Methods:We retrospectively reviewed medical records of all consecutive patients with solid tumors and a proven diagnosis of PJP according to the European Organization for Research and Treatment of Cancer (EORTC) consensus definitions. Patients were randomly grouped into a discovery cohort and a validation cohort in a 2:1 ratio. Propensity score matching was performed in a 1:2 ratio between patients with PJP and those without PJP. Demographic and clinical data were collected, which included malignancy types, baseline NLR, chest imaging, coexisting pulmonary disease, and treatment regimens. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of NLR for analyzing risk of PJP. Multivariate logistic analysis was performed to identify the risk factors of PJP. Results:A total of 249 patients were included, of whom 83 had PJP infection and 166 did not. A total of 157 (63.1%) patients were aged 65 years or older, 73.5% of participants were male, and 37.3% were never-smokers. Patients with PJP had a higher NLR level than those without PJP (P<0.001). The optimal threshold of NLR to predict PJP was 6.22. Multivariate analysis revealed independent associations with higher NLR (odds ratio: 4.96; 95% confidence interval: 1.82-13.50; P=0.002) and PJP after adjustment for age, sex, and smoking status. The incidence of PJP in the high-NLR subgroup (NLR ≥6.22) was significantly higher than that in the low-NLR subgroup (NLR <6.22) in the discovery (65.3% vs. 19.8%; P<0.001) and validation cohorts (65.4% vs. 19.0%; P<0.001). Moreover, NLR was negatively correlated with absolute CD4 and CD8 cell count. Patients with high NLR had a lower mean absolute CD4 and CD8 cell count than those with low NLR. Conclusions:Among patients with solid tumors, a baseline feature of high NLR (≥6.22) was independently associated with an increased risk of PJP development. Furthermore, the NLR demonstrates potential utility in assessing immune status. Therefore, clinicians should consider initiating PJP prophylaxis earlier or performing earlier PJP screening in patients with solid tumors and elevated peripheral blood NLR.

Background:MET exon14 skipping mutations (METex14) is an established actionable driver oncogene of non-small-cell lung cancer (NSCLC). While ensartinib is a known second-generation tyrosine kinase inhibitor with primary activity against ALK translocation, it is also classified as a type Ia MET inhibitor. We have previously shown anti-tumor activity against METex14 positive NSCLC both in vivo and in vitro. The EMBRACE trial aims to evaluate the clinical efficacy and safety of ensartinib for treatment of METex14 positive NSCLC. Methods:This is a multicenter single arm phase II investigator-initiated study that enrolled METex14 positive lung cancer after failing first line chemotherapy and/or immunotherapy. Eligible patients received ensartinib 225 mg orally once daily in a continuous 28-day treatment cycle until disease progression, unacceptable side effect, or death. Primary endpoint was investigator-assessed objective response rate (ORR), and the secondary end point included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR) and safety profiles. The study was registered with the Chinese Clinical Trial Registry (ChiCTR2100048767). Findings:From July 2021 to February 2024, a total of 31 patients were enrolled and received ensartinib. Median follow-up time of the 30 evaluable patients was 9.2 months (95% Confidence Interval [CI], 6.3-not estimable). The ORR was 53.3% (16/30; 95% CI, 35.5-71.2) and DCR was 86.7% (26/30; 95% CI, 74.5-98.8). Median PFS was 6.0 months (95% CI, 3.0-8.8) and median DoR was 7.9 months (95% CI, 4.8-8.7). Adverse events (AEs) were reported in 24 patients (80%), with 7 (23.3%) of grade 3. The most common AEs were rash (14/30, 46.7%), followed by anemia (7/30, 23.3%), increased ALT (7/30, 23.3%), increased AST (7/30, 23.3%), and pruritus (6/30, 20%). No serious adverse events or treatment-related deaths occurred. Importantly, the exploratory ctDNA analysis indicates that clearance of circulating tumor DNA (ctDNA) at four weeks treatment was associated with more favorable treatment outcomes comparing with patients having positive ctDNA. Interpretation:Ensartinib has a promising anti-tumor activity and manageable safety in previously treated patients with METex14 positive lung cancer. Funding:This work was supported by the National Natural Science Foundation of China [82370028, 82422001] and the CSCO-MET Aberrant Solid Tumor Research Grant [Y-2022METAZMS-0066].

INTRODUCTION:Amivantamab plus lazertinib significantly improved progression-free and overall survival versus osimertinib in patients with previously untreated, EGFR-mutant advanced NSCLC. EGFR-targeted therapies are associated with dermatologic adverse events (AEs), which can affect quality of life (QoL). COCOON was conducted to assess prophylactic management and improve treatment experience. METHODS:In the phase 2 COCOON study (NCT06120140), participants with previously untreated, EGFR-mutant, locally advanced or metastatic NSCLC received intravenous amivantamab plus oral lazertinib and were randomized 1:1 to enhanced dermatologic management (COCOON DM) or standard of care (SoC DM) per local guidelines. COCOON DM included oral doxycycline or minocycline (100 mg twice daily; weeks 1-12), clindamycin 1% (on scalp daily; weeks 13-52), chlorhexidine 4% (on fingernails and toenails daily), and ceramide-based moisturizer (on body and face at least daily). Primary end point was incidence of grade 2 or higher dermatologic AEs of interest (DAEIs) by week 12. RESULTS:In total, 201 participants were randomized (99 to COCOON DM and 102 to SoC DM). At a median follow-up of 7.1 months, COCOON DM demonstrated significant reduction in the primary end point versus SoC DM (42% versus 75%; OR, 0.24; 95% confidence interval, 0.13-0.45; p < 0.0001). By week 12, the largest benefit with COCOON DM was observed in DAEIs involving the face and body (excludes paronychia; 26% versus 60%; p < 0.0001) and DAEIs involving the scalp (10% versus 26%; p = 0.0049). This benefit was maintained at 6 months, with significant reductions of DAEIs involving face, body, and scalp (excluding paronychia). Patient-reported outcomes favored COCOON DM, indicating reduced impact of dermatologic symptoms on QoL. CONCLUSION:An uncomplicated, widely available, prophylactic regimen (COCOON DM) reduced the incidence of DAEIs with amivantamab-lazertinib and the impact of symptoms on QoL.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective in non-small-cell lung cancer (NSCLC) with sensitizing mutations. However, patients with uncommon EGFR mutations show variable responses, and resistance often develops. The C797S mutation is a common resistance mechanism after third-generation EGFR-TKI osimertinib therapy, with no standard treatment established. A 37-year-old Chinese woman with advanced NSCLC harboring EGFR G719S/S768I mutations developed an acquired C797S mutation without T790M after second- and third-generation EGFR-TKI therapy. She was treated with a combination of gefitinib and bevacizumab, achieving a partial response, particularly in liver metastases. Her overall survival exceeded 60 months. Gefitinib combined with bevacizumab demonstrates efficacy in managing NSCLC with uncommon EGFR mutations and overcoming acquired C797S resistance. This combination therapy offers a promising treatment strategy for patients with limited options after resistance to second- and third-generation EGFR-TKIs.