Real-world comparative effectiveness of sotorasib versus docetaxel in second line and beyond among patients with advanced non-small cell lung cancer (NSCLC).

OBJECTIVES: To evaluate the comparative effectiveness of sotorasib monotherapy versus docetaxel as monotherapy or combination therapy in patients with pretreated KRAS G12C-mutated advanced NSCLC in the real-world. METHODS: A US-based electronic health record-derived de-identified database was used in this study. Patients with pretreated KRAS G12C-mutated advanced NSCLC who initiated sotorasib between May 28, 2021, and September 30, 2022, and docetaxel between January 1, 2019, and September 30, 2022 (to enhance sample size), were included, with a minimum of 12-month opportunity for follow-up. Treatment groups were balanced via overlap weighting propensity score methods. Median OS in the 2L and 2L+ settings were calculated using Kaplan-Meier estimates. Hazard ratios (HRs) were estimated via Cox proportional hazard models. RESULTS: Overall, the clinical characteristics in sotorasib and docetaxel cohorts were balanced after propensity score weighting. At baseline, most patients were > 65 years of age, had ECOG performance status of 0-1, were from the community practice setting, had advanced stage at initial diagnosis, and had prior anti-PD-(L)1 treatment and/or platinum-based chemotherapy. In the 2L setting, the median OS (95 % CI) for sotorasib (N=102) and docetaxel (N=58) patients was 10.2 (7.6-16.3) and 6.0 (4.2-11.0) months, respectively, with a corresponding mortality HR (95 % CI) of 0.62 (0.41-0.93). In the 2L+ setting, the median OS (95 % CI) for sotorasib (N=164) and docetaxel (N=116) was 10.2 (8.0-14.6) and 7.2 (5.1-10.6) months, respectively, with a corresponding mortality HR (95 % CI) of 0.65 (0.49-0.87). In patients with prior anti-PD-(L)1 treatment, the mortality HR (95 % CI) in the sotorasib group versus docetaxel was 0.61 (0.39-0.94) and 0.65 (0.48-0.89) in the 2L and 2L+ settings, respectively. Findings from other subgroups were consistent with the primary analyses. CONCLUSION: In this real-world comparative analysis of patients with pretreated KRAS G12C-mutated advanced NSCLC, sotorasib monotherapy demonstrated a longer median OS compared to docetaxel monotherapy or combination therapy.

Feasibility Study of Nivolumab in Combination with Carboplatin Plus Paclitaxel and Concurrent Thoracic Radiation in Patients with Untreated Unresectable Locally Advanced Non-Small Cell Lung Cancer.

Despite advancements in diagnosing and treating non-small cell lung cancer (NSCLC), the prognosis remains poor. Immune checkpoint inhibitors have shown promise in enhancing survival rates. Therefore, this study aimed to investigate the safety of nivolumab administration with concurrent chemoradiation therapy (CCRT) in patients with unresectable locally advanced NSCLC. Twelve patients with unresectable locally advanced NSCLC at Kansai Medical University Hospital and Izumi City General Medical Center were enrolled from May 2018 to September 2020. They received nivolumab (360 mg) tri-weekly twice, weekly carboplatin (AUC 2 min × mg/mL) and paclitaxel (40 mg/m2) for 6 weeks, and thoracic radiotherapy (60 Gy/30 fractions), followed by maintenance nivolumab therapy (360 mg, tri-weekly) for 6 months. The primary endpoint was incidence of dose-limiting toxicities (DLTs), and the secondary endpoints included safety, response rate, progression-free survival (PFS), overall survival (OS), 2-year survival rate, and treatment completion rate. Three patients completed the protocol. Nine discontinued due directly to interstitial pneumonia (three) and pneumonia (one). Ten patients (83.3%) experienced a grade 3 or higher event, of which three (25%) experienced a grade 4 or higher event, and of these, one (8.3%) experienced a grade 5 event. Three patients experienced DLTs. Concurrent nivolumab with CCRT was tolerated in unresectable locally advanced NSCLC, which offers potential treatment benefits.

A comparative study of the efficacy and safety of PD-1/L1 inhibitor and platinum-containing dual-agent chemotherapy in patients with advanced non-small cell lung cancer resistant to EGFR-TKIs.

OBJECTIVE: To assess the efficacy and safety of combining Programmed Death-1/Programmed Death-Ligand 1 (PD-1/L1) inhibitors with platinum-containing chemotherapy for treating late-stage Non-Small Cell Lung Cancer (NSCLC) patients who have developed resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs). METHODS: A retrospective analysis was conducted at Baoji Traditional Chinese Medicine Hospital involving 133 patients with advanced NSCLC who had shown resistance to EGFR-TKIs and were treated from October 2018 to May 2021. The cohort was categorized into two groups: one treated with immune checkpoint inhibitors (ICIs) plus chemotherapy and antiangiogenic agents (ICIs+BCP group), and the other treated with ICIs alone (ICIs group). Baseline data collected included demographic factors, smoking status, PD-L1 Tumor Proportion Score (TPS), EGFR mutation, Eastern Cooperative Oncology Group (ECOG) score, and routine blood markers prior to second-line therapy. Computed Tomography (CT) scans were performed every two treatment courses to evaluate the treatment efficacy. RESULTS: The ICIs+BCP group exhibited a statistically significant improvement in Overall Survival (OS) compared to the ICIs group (P=0.001). Cox survival analysis uncovered age (P=0.012), PD-L1 TPS expression (P<0.001), treatment regimen (P=0.006), Neutrophil-to-Lymphocyte Ratio (NLR) (P=0.024), and Platelet-to-Lymphocyte Ratio (PLR) (P=0.005) as independent factors influencing OS in patients with advanced NSCLC resistant to primary-line EGFR-TKI therapy. The nomogram model, based on these prognostic factors, exhibited Area Under the Curve (AUC) values of 0.823 and 0.769, indicating its predictive accuracy for 1-year and 2-year survival, respectively. CONCLUSION: Combining ICIs with BCP prolongs OS in patients with NSCLC resistant to EGFR-TKIs. This study underscores the importance of personalized treatment plans and biomarker evaluations to improve outcomes in drug-resistant cases.

Analysis of the effect of baseline detection and early clearance of ct-DNA, on survival outcomes among patients with advanced EGFR-mutant non-small cell lung cancer.

BACKGROUND: To determine if circulating tumor DNA (ct-DNA) dynamics of epidermal growth factor receptor (EGFR) mutation in plasma can identify a subset of patients with EGFR-mutant (EGFR- m) non-small cell lung cancer (NSCLC) with inferior survival outcomes, we analyzed and compared survival outcomes among patients with and without baseline presence and early clearance of EGFR ct-DNA in plasma. MATERIAL AND METHODS: For 66 patients newly dia-gnosed with EGFR- m NSCLC, plasma samples were collected at baseline and 1st response assessment at 12-24 weeks for extraction of ct-DNA. Estimation of ct-DNA (EGFR exons 18, 19, 20 and 21) was done using droplet digital polymerase chain reaction (dd-PCR) on the QX200 ddPCR system (BioRad, USA). Patients with detectable EGFR ct-DNA at baseline (sample 1), with either undetectable or persistent detectable ct-DNA in sample 2 were classified as clearers and non-clearers, respectively. RESULTS: Fifty-three patients received 1st/ 2nd generation EGFR tyrosine kinase inhibitors (TKIs) and 13 received either 3rd generation TKI (osimertinib) or chemotherapy plus gefitinib. The baseline ct-DNA-positive group had more patients with extra thoracic disease (60.4 vs. 48.5%). For the entire cohort, there was no difference in median progression-free survival (PFS) among baseline ct-DNA-negative (13.57 months) vs. ct-DNA-positive patients (12.32 months) (HR 0.74). There was a significant improvement of PFS among early ct-DNA clearers vs. non-clearers (12.32 vs. 9.92 months; HR 0.57). For those treated with 1st/ 2nd generation EGFR TKIs, this improvement in median PFS among early ct-DNA clearers vs. non-clearers was more apparent (11.76 vs. 6.8 months; HR 0.34). CONCLUSIONS: Baseline detection of the presence of ct-DNA of EGFR mutation in plasma was not predictive of first-line PFS, but is associated with extra thoracic disease. Patients with EGFR mutation and persistence of ct-DNA at first follow-up have worse PFS and overall survival (OS) in comparison to those clearing the same in plasma, especially among those treated with 1st/ 2nd generation EGFR TKIs.

Efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients with rare KRAS mutations: a real-world retrospective study.

Background: Kirsten rat sarcoma homolog (KRAS) mutations are one of the key drivers in non-small cell lung cancer (NSCLC) and FDA-approved specific inhibitors of KRAS-G12C mutation are available clinically. However, inhibitors of certain KRAS mutation subtypes remain unavailable, especially rare KRAS mutations including G13C, G13D, and Q61H. In this study, we retrospectively investigated the outcomes of NSCLC patients with rare KRAS-mutation to determine if they may benefit from immune checkpoint inhibitors (ICIs). Methods: Our retrospective study involved 240 advanced NSCLC patients with KRAS mutations, who visited Shanghai Chest Hospital from July 2018 to July 2021. Complete clinical and pathological data were recorded and progression-free survival (PFS) and overall survival (OS) were adopted as primary endpoints. Results: The median follow-up time was 36.5 months (range, 30.8-42.1 months) and the median OS was 9.7 months (range, 7.6-11.8 months). Of the 240 patients evaluated, 130 (54.2%) received chemotherapy and 110 (45.8%) received ICI-based treatment. Among the patients who received chemotherapy, patients with rare KRAS-mutations presented worse survival outcomes (median PFS, 3.4 vs. 4.1 months, P=0.047; median OS, 5.2 vs. 7.1 months, P=0.02) than conventional KRAS-mutant patients. PFS and OS of rare KRAS-mutation patients were prolonged after immunotherapy (median PFS 7.3 vs. 3.4 months, P<0.001; median OS, 13.3 vs. 5.2 months, P<0.001) and had no significant difference compared with conventional KRAS-mutant patients, in part of them whose programmed death-ligand 1 (PD-L1) expression data before immunotherapy were available (n=72), patients with a higher rate of PD-L1 positive tumor cells (≥50%) presented elevated PFS and OS. Conclusions: Despite having potential survival disadvantage compared with other NSCLC patients, rare KRAS-mutant patients (other than G12A, C, D, V) could benefit specifically from ICI-based therapy and survival outcomes are correlated with PD-L1 expression.

Adjuvant Chemotherapy in Addition to Neoadjuvant Chemotherapy for Locally Advanced Non-small Cell Lung Cancer.

BACKGROUND/AIM: The prognostic impact of adjuvant cytotoxic chemotherapy for patients with resectable locally advanced non-small cell lung cancer (NSCLC) who underwent surgery after neoadjuvant chemotherapy remains unclear. PATIENTS AND METHODS: A retrospective chart review was performed to identify patients who underwent surgery following neoadjuvant therapy for clinical T3N0 or N1-N2 resectable NSCLC between 2011 and 2016 at our hospital. Survival outcomes were analyzed with the Kaplan-Meier method and a Cox proportional hazard model. RESULTS: Thirty-eight patients were identified. The median recurrence-free survival (RFS) was 50.6 months and overall survival (OS) was 75.2 months. Patients who had undergone adjuvant chemotherapy were not associated with a favorable RFS (hazard ratio=1.01, p=0.98) or OS (hazard ratio=0.72, p=0.55), as compared with those who had not. However, subgroup analysis revealed that hazard ratio based on RFS and OS varied greatly between subgroups, suggesting that selected patients might benefit from adjuvant therapy, while others might be harmed by it. For example, in surgical-pathological stage III disease, adjuvant therapy showed a favorable RFS (HR=0.22, 95%CI=0.02-2.57, p=0.23) and OS (HR=0.36, 95%CI=0.03-4.01, p=0.40). Conversely, in surgical-pathological stage 0-II disease, adjuvant therapy showed an unfavorable RFS (HR=1.40, 95%CI=0.49-3.96, p=0.53) and OS (HR=0.95, 95%CI=0.29-3.12, p=0.93). CONCLUSION: Regardless of the negative findings in our overall patient cohort, our results may be beneficial in identifying patients who may likely benefit from adjuvant therapy. This contribution could assist the planning of large-scale prospective studies.

Enhancing safety and therapeutic efficacy: PD-1 inhibitor and recombinant human endostatin combination in advanced non-small cell lung cancer patients.

OBJECTIVE: To assess the therapeutic efficacy of combining a programmed death-1 (PD-1) inhibitor with recombinant human endostatin in patients diagnosed with advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively collected data from 83 patients with advanced NSCLC who received treatment at Xi'an Daxing Hospital between May 2020 and July 2022. Among them, 42 patients were treated with a PD-1 inhibitor combined with recombinant human endostatin (observation group), while 41 patients received PD-1 inhibitor monotherapy (control group). We evaluated the objective response rate, changes in serum tumor markers pre- and post-treatment, occurrence of adverse reactions, progression-free survival (PFS), 1-year survival rate, and identified independent risk factors affecting prognosis in both groups. RESULTS: The treatment efficacy in the observation group significantly surpassed that in the control group. Following treatment, the levels of cytokeratin 19 fragment antigen 21-1, carcinoembryonic antigen, and carbohydrate antigen 125 decreased significantly in the observation group compared to the control group (P < 0.001). There was no notable difference in the incidence of adverse reactions between the two groups (P < 0.001). The median PFS and 1-year survival rate were notably higher in the observation group (P < 0.001). Age, liver metastasis, and treatment regimen emerged as independent risk factors affecting poor prognosis in patients (P < 0.001). CONCLUSION: Combining a PD-1 inhibitor with recombinant human endostatin in patients with advanced NSCLC not only enhances clinical efficacy but also increases PFS and the 1-year survival rate while ensuring treatment safety. This combination therapy shows promise for clinical application.

The impact of different modalities of chemoradiation therapy and chemotherapy regimens on lymphopenia in patients with locally advanced non-small cell lung cancer.

Background: Chemotherapy and radiotherapy (RT) would induce lymphopenia, leading to a poor prognosis. This study investigated whether chemotherapy increased lymphopenia during RT and explored the impacts of different chemotherapy regimens on the lymphocyte counts of patients receiving RT. Methods: Clinical parameters and lymphocyte data were collected from 215 patients with locally advanced non-small cell lung cancer (LA-NSCLC). Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) of ≤0.2×103 cells/µL. Patient overall survival (OS) was analyzed using the Kaplan-Meier method. The predictors of SRL were extracted using univariate and multivariate regression analyses with backward likelihood ratio elimination. Results: Compared with patients without SRL, patients with SRL with LA-NSCLC showed a poorer prognosis in terms of OS (P=0.003). Of the 215 patients, 130 underwent concurrent chemoradiotherapy (CCRT) and 85 underwent sequential chemoradiotherapy (SCRT). The OS was better in patients without SRL (in the CCRT group, P=0.01 and in the SCRT group, P=0.08). The mean ALCs for CCRT and SCRT did not differ significantly (P=0.27). The minimum ALC of CCRT was significantly lower than that of SCRT (P<0.0001). CCRT was a predictor of SRL (P=0.008). However, multivariate analysis showed that the different chemotherapy regimens were not predictors of SRL (all P>0.1). Conclusions: In LA-NSCLC, the outcomes of patients with SRL were poorer than those without SRL. RT and chemotherapy were the main factors affecting SRL development, while different chemotherapy regimens were not significantly associated with lymphocyte counts in LA-NSCLC.

Spatial tertiary lymphoid structures imply response to anti-PD-1 plus anlotinib in advanced non-small cell lung cancer.

Despite breakthroughs of immunotherapy synergistically combined with blockade of vascular endothelial growth factor receptor, several patients with advanced non-small cell lung cancer (NSCLC) experience non-response or followed relapse. Organized lymphoid aggregates, termed tertiary lymphoid structures (TLSs), are found to be associated with improved response to immunotherapy. Here, we explore the landscapes of TLSs in tumour tissues from a real-world retrospective study. Our investigation showed that with a median follow-up of 11.2 months, the ORR was 28.6% (18/63, 95% CI 17.9-41.3) and the median PFS was 6.1 (95% CI 5.5-6.6) months in NSCLC patients treated with PD-1 blockade combined with anlotinib. By multiplex immunofluorescence (mIF) analysis, spatially, more TLSs and high CD20+ B-cell ratio in TLSs were associated with higher ORR. High density of intratumoral CD8+ T cells showed better ORR and PFS. The numbers of CD8+ T cells with a distance within 20 µm and 20-50 µm between tumour cells were higher in responders than non-responders. But responders had significantly higher TLSs within 20 µm rather than within 20-50 µm of tumour cells than non-responders. The inflamed immunophenotyping occupied higher proportions in responders and was associated with better PFS. Besides, tumour cells in non-responders were found more temporal cell-in-cell structures than responders, which could protect inner cells from T-cell attacks. Taken together, landscape of TLSs and proximity architecture may imply superior responses to PD-1 blockade combined with anlotinib for patients with advanced non-small cell lung cancer.

Long-term outcome of definitive radiotherapy for locally advanced non-small cell lung cancer: A real-world single-center study in the pre-durvalumab era.

BACKGROUND: There was limited research data on large-scale locally advanced non-small cell lung cancer (LA-NSCLC) radical radiotherapy (RT) reported in China. This study examined overall survival (OS), progression-free survival (PFS), treatment effectiveness, and toxicity in patients with LA-NSCLC treated with definitive RT in the pre-durvalumab era. METHODS: A retrospective analysis of demographic information, clinical characteristics, treatment patterns, and clinical outcomes of 789 patients with LA-NSCLC who underwent radical RT at our center between January 2005 and December 2015 was performed. The Kaplan-Meier method and log-rank test were used for survival comparisons, and Cox regression was used for multivariate analysis. RESULTS: There were 328 patients with stage IIIA disease and 461 with stage IIIB disease. By the last follow-up, there were 365 overall deaths and 576 cases of recurrence, metastasis, or death. The median survival time was 31 months. The OS rates at 1, 2, 5, and 10 years were 83.7%, 59.5%, 28.8%, and 18.9%, respectively. PFS rates at 1, 2, 5, and 10 years were 48%, 24.5%, 11.9%, and 5.5%, respectively. Rates of ≥grade 3 acute radiation pneumonitis or esophagitis were 7.6% and 1.9%, respectively. Rates of ≥grade 3 chronic radiation pneumonitis and esophagitis were 11% and 0.4%, respectively. Multivariate analysis showed that the Karnofsky Performance Status (KPS) score, smoking status, and combined chemotherapy were prognostic factors for OS (p < 0.05). Multivariate analysis revealed that combined chemotherapy and radiation dose were prognostic factors for PFS (p < 0.05). CONCLUSIONS: Our center's data showed that the survival prognosis of locally advanced patients receiving RT and chemotherapy in China was consistent with international levels during the same period. Patients with a KPS score of 80 or higher, who had never smoked or received combined RT, had a more favorable prognosis than those with a KPS of less than 80, who had smoked, or only received RT. The combination of RT and chemotherapy, with a reasonable radiation dose, was the key to improving the therapeutic effect.

Optimization of treatment strategies for elderly patients with advanced non-small cell lung cancer.

Lung cancer stands as a malignant neoplasm bearing the highest burden of morbidity and mortality within the elderly population on a global scale. Among the lung cancer subtypes, non-small cell lung cancer (NSCLC) prevails as the most prevalent. As age advances, elderly patients often present with an increased prevalence of comorbidities, diminished organ reserve function, and alterations in drug pharmacokinetics, including absorption, distribution, metabolism, and clearance. These factors collectively contribute to a reduction in their capacity to tolerate therapeutic interventions. Regrettably, there exists a paucity of research data and evidence regarding the management of elderly patients afflicted by advanced lung cancer. This article endeavors to compile and elucidate strategies for the enhancement of treatment approaches, with the aim of aiding clinical decision-making. Prior to the selection of clinical treatment modalities for elderly patients with advanced NSCLC, a comprehensive assessment should be conducted, taking into account various facets, including tumor characteristics, patient age, physiological status, and the presence of comorbidities. The treatment strategy should be implemented in a tiered fashion, thereby affording the opportunity for the tailoring of individualized therapeutic approaches for elderly patients afflicted by advanced NSCLC. The demographic of elderly patients confronting advanced NSCLC presents a complex landscape marked by intricate underlying conditions, necessitating the imperative optimization of treatment strategies.

Treatment sequences in EGFR mutant advanced NSCLC.

Common EGFR gene mutations (exon 19 deletion and L858R in exon 21) are the most frequent cause of actionable genomic alterations in non-small cell lung cancer (NSCLC) patients. The introduction of EGFR tyrosine kinase inhibitors (TKIs) as 1st-line treatment of advanced stages of the disease has changed the natural history of the disease and extended survival rates, establishing third generation TKIs as a new standard of frontline treatment. Nonetheless, the prolongation of overall survival remains modest, as multiple escape pathways and tumor increasing heterogeneity inevitably develop over time. Several strategies are currently developed to improve these patients' outcome: prevent the emergence of resistance mechanisms by therapeutic combinations introduced from the first line, act on the residual disease at the time of maximum response to 1st line treatment, develop therapeutic strategies at the time of acquired resistance to TKIs, either dependent on the resistance mechanisms, or agnostic of the resistance pathways. Recent advancements in treatment combinations have shown promising results in prolonging progression-free survival, but often at the cost of more severe side effects in comparison with the current standard of care. These emerging new treatment options open up possibilities for diverse therapeutic sequences in the management of advanced NSCLC depending on common EGFR mutations. The impact on the disease natural history, the patients' survival and quality of life is not yet fully understood. In this review, we propose an overview of published and forthcoming advances, and a management algorithm considering the different first-line options, integrating the clinical and biological parameters that are critical to clinicians' decision-making process.

Reduced frequency and severity of radiation esophagitis without marginal failure risk by contralateral esophagus sparing IMRT in stage III non-small cell lung cancer patients undergoing definitive concurrent chemoradiotherapy.

PURPOSE: Radiation esophagitis is frequent and annoying toxicity in high dose thoracic radiation therapy. Contalateral esophagus sparing intensity modulated radiation therapy (CES-IMRT) has been proposed to mitigate this problem, and this is to report the impact of CES-IMRT in definitive concurrent chemoradiotherapy (dCCRT) for lung cancer patients. MATERIALS AND METHODS: From January 2021 till May 2023, 183 stage III non-small cell lung cancer patients underwent dCCRT. Esophagus was located within 1 cm from internal target volume in 159 patients. We comparatively evaluated the frequency and severity of esophagitis by pain-killer usage, analgesic quantification algorithm (AQA) score, and failure patterns in 159 CES-necessary patients. RESULTS: All patients underwent dCCRT (66 Gy in 30 fractions with concurrent chemotherapy). Actual CES-IMRT application was determined based on the discretion of responsible radiation oncologists: CES-applied in 41 patients; and CES-unapplied in 118. CES-applied patients experienced pain events less frequently (pain-killer usage: 53.7 % vs. 77.1 %, p = 0.008) and less severely (AQA score of 2-3: 39.0 % vs. 68.6 %, p = 0.002). On multivariate analyses, overlapping volume of esophagus and planning target (HR = 1.32, 95 % CI 1.12-1.55, p = 0.001) and CES-IMRT application (HR = 0.31, 95 % CI 0.13-0.76, p = 0.010) were associated with AQA score of 2-3 less frequently. There were no differences in failure pattern, progression-free survival, and overall survival. CONCLUSIONS: CES-IMRT application resulted in less frequent and less severe pain events without compromising oncologic outcomes. Further studies, preferably in a randomized fashion, would be desired.

Healthcare Resource Utilization and Associated Costs among Patients with Advanced Non-Small-Cell Lung Cancer Receiving Chemotherapy or Immunotherapy in Spain: A Single-Center, Real-World, Exploratory Study.

The objective of this observational, single-center, retrospective study conducted in a Spanish tertiary hospital was to describe the real-world (RW) healthcare resource utilization (HCRU) among patients with advanced non-small-cell lung cancer (aNSCLC) who received chemotherapy (CT) or immunotherapy (IT) as first and second lines of treatment. A total of 173 patients diagnosed with aNSCLC and treated between January 2016 and August 2020 were included. The standardized average costs per patient/year were EUR 40,973.2 and EUR 22,502.4 for first-line CT and IT and EUR 140,601.3 and EUR 20,175.9 for second-line CT and IT, respectively. The average annual costs per patient associated with adverse-event (AE) onset were EUR 29,939.7 and EUR 460.7 for first-line CT and IT and EUR 35,906.4 and EUR 3206.1 for second-line CT and IT, respectively. The costs associated with disease management were EUR 33,178.0 and EUR 22,448.4 for first-line CT and IT and EUR 127,134.2 and EUR 19,663.9 for second-line CT and IT, respectively. In conclusion, IT use showed a lower average annual cost per patient, which was associated with lower HCRU for both disease and AE management, compared to the use of CT. However, these results should be further confirmed in the context of the currently implemented treatment schemes, including the combination of CT with single or dual IT.

The combination of tumor mutational burden and T-cell receptor repertoire predicts the response to immunotherapy in patients with advanced non-small cell lung cancer.

Tumor mutational burden (TMB) and T-cell receptor (TCR) might predict the response to immunotherapy in patients with non-small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB-and-TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (n = 17) and validation set (n = 21). A higher TMR score was associated with better response and longer progression-free survival to immunotherapy in both the discovery set and validation set. The performance of TMR score was confirmed in the two external validation cohorts of 225 NSCLC patients and 306 NSCLC patients. Tumors with higher TMR scores were more likely to combine with LRP1B gene mutation (p = 0.027) and top 1% CDR3 sequences (p = 0.001). Furthermore, LRP1B allele frequency was negatively correlated with the top 1% CDR3 sequences (r = -0.55, p = 0.033) and positively correlated with tumor shrinkage (r = 0.68, p = 0.007). The TMR score could serve as a potential predictive biomarker for the response to immunotherapy in advanced NSCLC.

Clinical Association Between Immune-related Adverse Events and Treatment Efficacy in Patients With Non-small-cell Lung Cancer Treated With Nivolumab-Ipilimumab-based Therapy.

BACKGROUND/AIM: Nivolumab and ipilimumab combination therapy has been extensively explored for the treatment of advanced non-small-cell lung cancer (NSCLC) through the pivotal phase III trials CheckMate 227 and CheckMate 9LA. However, the relationship between immune-related adverse events (irAEs) and the effectiveness of nivolumab plus ipilimumab-based therapy in a real-world clinical setting remains uncertain. PATIENTS AND METHODS: We performed a retrospective analysis of 28 patients with advanced or recurrent NSCLC who underwent treatment with nivolumab plus ipilimumab, with or without platinum-doublet chemotherapy, from February 2021 to January 2023. The primary objective was to elucidate the clinical association between irAEs and treatment efficacy associated with nivolumab plus ipilimumab-based therapy. RESULTS: Among the 28 patients, 22 (78.6%) experienced irAEs. The median progression-free survival (PFS) was significantly longer for patients with irAEs than for those without (p=0.0158), as was overall survival (OS) (p=0.000394). The severity of irAEs had no significant influence on PFS or OS. The objective response rate tended to be higher in patients with irAEs than in those without (50.0% versus 0.0%, respectively; p=0.0549). Multivariate analysis indicated that irAE occurrence was an independent factor for improved PFS (hazard ratio=0.2084, p=0.01383) and OS (hazard ratio=0.0857, p=0.001588). Interstitial lung disease was inferior to other irAE profiles for both PFS and OS. CONCLUSION: Patients with advanced NSCLC experiencing irAEs demonstrated superior clinical outcomes when treated with nivolumab plus ipilimumab-based therapy compared with those without irAEs. However, immune-related interstitial lung disease may be less linked with PFS and OS than other irAE profiles.

Real-world outcomes on platinum-containing chemotherapy for EGFR-mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors.

Background: Front-line therapy with an EGFR tyrosine kinase inhibitor (TKI) is the standard of care for treating patients with advanced nonsquamous NSCLC with the common sensitizing EGFR exon 19 deletion and exon 21 L858R point mutations. However, EGFR TKI resistance inevitably develops. The optimal subsequent therapy remains to be identified, although platinum-containing chemotherapy regimens are often administered. Our objectives were to describe baseline characteristics, survival, and subsequent treatment patterns for patients with advanced nonsquamous NSCLC with EGFR exon 19 deletion or L858R mutation who received a platinum-based combination regimen after front-line EGFR TKI therapy. Methods: This retrospective study used a nationwide electronic health record-derived deidentified database to select adult patients with advanced nonsquamous NSCLC, evidence of EGFR exon 19 deletion or L858R mutation, and ECOG performance status of 0-2 who initiated platinum-containing chemotherapy, with or without concomitant immunotherapy, from 1-January-2011 to 30-June-2020 following receipt of any EGFR TKI as first-line therapy or, alternatively, a first- or second-generation EGFR TKI (erlotinib, afatinib, gefitinib, dacomitinib) as first-line therapy followed by the third-generation EGFR TKI osimertinib as second-line therapy. Data cut-off was 30-June-2022. The Kaplan-Meier method was used to estimate overall survival (OS) after initiation of pemetrexed-platinum (n=119) or any platinum-based combination regimen (platinum cohort; n=311). Results: The two cohorts included two-thirds women (65%-66%) and 57%-58% nonsmokers; median ages were 66 and 65 years in pemetrexed-platinum and platinum cohorts, respectively. Median OS was 10.3 months (95% CI, 8.1-13.9) from pemetrexed-platinum initiation and 12.4 months (95% CI, 10.2-15.2) from platinum initiation; 12-month survival rates were 48% and 51%, respectively; 260 patients (84%) had died by the end of the study. Conclusion: The suboptimal survival outcomes recorded in this study demonstrate the unmet need to identify more effective subsequent treatment regimens for patients with EGFR-mutated advanced nonsquamous NSCLC after EGFR TKI resistance develops.

Cost-effectiveness of Kang Ai injection plus chemotherapy vs. Shenqi Fuzheng injection plus chemotherapy in the first-line treatment of advanced non-small cell lung cancer.

Objective: This study aimed to evaluate the cost-effectiveness of two Chinese patent medicines, including Kang Ai injection and Shenqi Fuzheng injection with each combined with platinum-based chemotherapy as the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) in China. Methods: From Chinese healthcare system perspective, a three state Markov model with a cycle of 3 weeks and a 10-year horizon was constructed to derive the incremental cost-effectiveness ratio (ICER). Since only individual patient data of progression-free survival (PFS) of Kang Ai injection group can be obtained, we extrapolated median overall survival (mOS) of Kang Ai injection group and median progression-free survival (mPFS) and mOS of Shenqi Fuzheng injection group based on published literature and methods. Then survival curves were estimated by the method of declining exponential approximation of life expectancy (DEALE), which is based on the assumption that survival follows a declining exponential function. We performed one-way sensitivity analysis and probabilistic sensitivity analysis to test the robustness. Additionally, a scenario analysis was adopted to investigate the impact of using best-fitting distribution for PFS curve of Kang Ai injection group on the economic conclusion. Results: The base-case result indicated that Kang Ai injection group provided 0.217 incremental quality-adjusted life years (QALYs) at an incremental cost of $103.38 compared with Shenqi Fuzheng injection group. The ICER was $476.41/QALY, which was much lower than the willingness to pay threshold of one time the GDP per capita of China in 2022 ($12,070/QALY). Deterministic sensitivity analysis result showed that ICER was most sensitive to the changes in odds ratio (OR) value. The probabilistic sensitivity analysis confirmed the robustness of base-case analysis results. The scenario analysis result showed that by using Log-Normal distribution to fit the PFS curve of Kang Ai injection group and shortening the time horizon to 5 years, the ICER was $4,081.83/QALY, which was still much lower than the willingness to pay threshold. Conclusion: Kang Ai injection combined with platinum-based chemotherapy appeared to be more cost-effective for the treatment of advanced NSCLC than Shenqi Fuzheng injection combined with platinum-based chemotherapy.

The Impact of Kinlessness on Survival in Patients With Advanced Non-small Cell Lung Cancer: A Single-Center Retrospective Study.

Objectives Among patients with advanced non-small cell lung cancer (NSCLC), there are those who do not have a spouse, family members, or friends to support them in their cancer treatment and daily life: the kinless patients. Therefore, we designed an exploratory study of kinlessness and the prognosis of advanced NSCLC. Methods We retrospectively analyzed the prognosis of clinical factors and treatment and kinlessness in patients with advanced NSCLC with wild-type or unknown status for epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) and who visited our hospital from November 2018 to February 2023. In addition to the survival analysis by kinlessness, a multivariable analysis of survival was performed for all clinical factors. In a secondary analysis, a multivariable analysis of the choice of best supportive care (BSC) was performed for all clinical factors. Results One hundred forty-four patients are included in our cohort. There were 131 patients with kin, with a median survival of 1.34 years (95% CI of 1.01-1.79 years). There were 13 patients has no kin, with a median survival of 0.53 years (95% CI 0.23-0.76 years). The log-rank analysis showed that kinless patients had significantly shorter overall survival than patients who have kin. A Cox regression analysis showed that age, distant metastasis, performance status, and kinlessness were associated with overall survival. Secondary analysis showed that there was no statistical association between kinlessness and the choice of BSC in our cohort. Conclusions Kinless patients had shorter survival than patients who have kin in our single-center, retrospective study of patients with advanced NSCLC with wild-type or unknown status for (EGFR/ALK). Further research to evaluate the clinical impact of kinlessness in the treatment of advanced NSCLC is needed.