Association of Immune-Related Adverse Events and the Efficacy of Anti-PD-(L)1 Monotherapy in Non-Small Cell Lung Cancer: Adjusting for Immortal-Time Bias.

Purpose: The association between immune-related adverse events (irAEs) and survival outcomes in non-small cell lung cancer (NSCLC) patients treated with programmed-death-(ligand)1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB). Materials and Methods: We retrospectively enrolled 425 advanced NSCLC patients who received anti-PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAE (n=127) and non-irAE (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark (2-, 3-, 6-, and 9-month) and time-dependent Cox analyses were performed to eliminate ITB. Results: With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs. 3.4 months, p<0.0001) and OS (31.4 vs. 14.0 months, p<0.0001), which persisted in landmark and time-dependent Cox analyses. For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival. Conclusion: After adequately adjusting ITB, the occurrence of overall irAEs predicts for favorable efficacy of anti-PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.

Nutritional status as prognostic factor of advanced oesophageal cancer patients treated with immune checkpoint inhibitors.

BACKGROUND & AIMS: Malnutrition is reported in 60%-85% of oesophageal cancer (EC) patients. Indicators commonly used in the clinic to evaluate the nutritional status of patients include haemoglobin (Hb), body mass index (BMI), albumin (ALB), prognostic nutritional index (PNI), prealbumin (PAB), transferrin (TRF), and NRS2002 scores. In this study, we explored the associations between pretreatment nutrition-related indicators and clinical outcomes in patients with advanced EC who were treated with immune checkpoint inhibitors (ICIs). METHODS: The general clinical data of patients, NRS2002 scores, PNI, and levels of BMI, ALB, Hb, PAB, and TRF at baseline were collected. Categorical variables were compared using the chi-squared test. The chi-squared test was used to compare the differences in the objective response rate (ORR) and the disease control rate (DCR) between groups. The Kaplan-Meier method was used to compute the survival curves. Cox proportional hazard regression was performed to evaluate factors independently associated with OS and PFS. RESULT: Of the 1340 patients diagnosed with EC at Zhejiang Cancer Hospital between June 2018 and September 2022, 354 patients with advanced EC who underwent ICI therapy were enrolled. In total, the ORR and DCR were 38.1% and 82.2%, respectively. A significantly worse response to ICI therapy was observed in the Hb-L group and the BMI-L group. The median PFS and OS among all enrolled patients were 6.0 months and 13.3 months, respectively. PFS was significantly associated with pretreatment levels of Hb, ALB, and PAB. OS was significantly associated with pretreatment levels of Hb, ALB, BMI, PNI, TRF, and PAB. The multivariate analysis further demonstrated that Hb was an independent prognostic factor of both OS (P = 0.004) and PFS (P = 0.047), and ALB was an independent prognostic factor of OS (P = 0.045). No independent relevance for OS or PFS was found in the BMI, PNI, TRF, or PAB groups. In this study, the NRS2002 scores was not significantly correlated with the therapeutic response or prognosis of ICI therapy. CONCLUSION: Our study indicated the relevance of nutritional status to the efficacy and prognosis of advanced EC patients treated with ICIs. The pretreatment levels of Hb and BMI were significantly related to therapeutic response. The pretreatment levels of Hb, BMI, ALB, PAB, TRF, and PNI were partially associated with survival. Notably, Hb is not only related to therapeutic response but is also an independent prognostic indicator of survival outcomes.

Small molecule multitarget antiangiogenic inhibitor treatments for advanced thymic epithelial tumors: A retrospective study.

BACKGROUND: Thymic epithelial tumors (TETs) are rare malignant tumors with limited treatment options. No established second-line treatment regimen is available following the preferred first-line chemotherapy, resulting in unsatisfactory efficacy and poor prognosis for patients with advanced TETs. This study aimed to evaluate the efficacy of small molecule multitarget antiangiogenic inhibitors as well as the prognostic factors for advanced TETs. METHODS: A retrospective study was conducted using data from a real-world database. Clinical information and survival follow-up data were collected from 52 patients with advanced TETs who received small molecule multitarget antiangiogenic inhibitors at Zhejiang Cancer Hospital between August 10, 2016 and August 10, 2022. The short-term efficacy of the treatments, survival time of the patients, and relevant prognostic factors of advanced TETs were analyzed. RESULTS: Out of the 52 patients included in this study, 16 had thymoma and 36 had thymic carcinoma. The 52 patients had an overall response rate of 21.1% and a disease control rate of 94.2%. In addition, the median progression-free survival (PFS) was 8.05 months, and the overall survival (OS) was 25.00 months. Apatinib was given to 33 patients, anlotinib to 15 patients, and sunitinib or lenvatinib to four patients. Only seven patients received antiangiogenic inhibitors as their first-line therapy, 27 patients as their second-line therapy, and 18 patients as third-line or subsequent therapy. Meanwhile, 42 patients received monotherapy with an antiangiogenesis inhibitor, while 10 patients received combination therapy. Univariate analysis indicated that the combined treatment was associated with a superior OS (p = 0.044); multivariate analysis indicated that the combined treatment was an independent prognostic factor for PFS (p = 0.014) and OS (p = 0.012). CONCLUSION: The findings suggest that small molecule multitarget antiangiogenic inhibitors are efficacious as second or post-line treatments as a viable alternative treatment option for patients with advanced TETs.