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Abstract Background and Aim Immune checkpoint inhibitors have significantly improved the clinical outcomes of many cancer types, but they induce a range of immune‐related adverse events (irAEs). Although adrenal insufficiency (AI) is a rare irAE, it can lead to serious consequences. This study aimed to determine the clinical features of patients with advanced non‐small‐cell lung cancer (NSCLC) who developed AI following pembrolizumab treatment. Methods We retrospectively reviewed and analyzed the clinical data of all patients with NSCLC treated with pembrolizumab at Juntendo University Hospital from February 2017 to December 2020. The diagnosis of AI was established based on the Endocrine Emergency Guidance for the acute management of endocrine complications of checkpoint inhibitor therapy in the UK and the clinical practice guidelines of the Japan Endocrine Society. Result AI was clinically suspected in 59 out of 186 patients treated with pembrolizumab, and 10 (5.4%) cases were confirmed. The symptoms included hyponatremia (n = 9), fatigue (n = 8), and loss of appetite (n = 6). All patients had low adrenocorticotropic hormone (ACTH) levels, and five patients were diagnosed with isolated ACTH deficiency. All patients completely recovered with corticosteroid replacement. The median time to onset of AI was 8.0 (range 3.8–15.2) months. The median progression‐free survival in these patients was 22.4 (95% confidence interval 11.2–not reached) months. Conclusion The incidence of AI among patients treated with pembrolizumab is more frequent than previously reported. In addition, secondary AI, especially isolated ACTH deficiency, is a major form of AI induced by pembrolizumab.

Abstract Background The combination of immune-checkpoint inhibitors with chemotherapy has become the standard of treatment for non-small cell lung cancer (NSCLC) patients. However, the association between therapeutic efficacy and the development of immune-related adverse events (irAEs) remains unclear in patients treated with combination therapy. We aimed to investigate the frequency of irAEs, and the association between therapeutic efficacy and the development of irAEs in patients with NSCLC. Materials and methods We retrospectively surveyed patients with chemo-naïve advanced NSCLC who received pembrolizumab plus platinum-based chemotherapy or pembrolizumab monotherapy at Juntendo University Hospital, Japan, between February 2017 and May 2021. Results Among 148 patients (median [range] age, 68 (33–85) years; 107 men [72.3%] and 41 women [27.7%]), 74 each received pembrolizumab plus chemotherapy and pembrolizumab monotherapy. IrAEs were observed in 46 (62.2%) and 41 patients (55.4%) in the combination therapy and monotherapy group, respectively. Patients with irAEs showed significantly longer progression-free survival (PFS) than those without irAEs in the combination therapy group (8.9 vs. 5.7 months; Hazard Ratio [HR], 0.53; 95% CI, 0.29–0.98; P = 0.041) and monotherapy group (11.7 vs. 5.0 months; HR, 0.40; 95% CI, 0.22–0.70; P = 0.001). In the multivariable analysis, development of irAEs was positively associated with PFS in both the groups (HR, 0.48; 95% CI, 0.26–0.89; P = 0.019 and HR, 0.38; 95% CI, 0.21–0.68; P

Abstract Background The prognosis of patients with NSCLC harboring oncogenic driver gene alterations, such as EGFR gene mutations or ALK fusion, has improved dramatically with the advent of corresponding molecularly targeted drugs. As patients were followed up for about five years in most clinical trials, the long-term outcomes beyond 5 years are unclear. The objectives of this study are to explore the clinical course beyond five years of chemotherapy initiation and to investigate factors that lead to long-term survival. Methods One hundred and seventy-seven patients with advanced, EGFR-mutated or ALK-rearranged NSCLC who received their first chemotherapy between December 2008 and September 2015 were included. Kaplan Meier curves were drawn for the total cohort and according to subgroups of patients’ characteristics. Results Median OS in the total cohort was 40.6 months, the one-year survival rate was 89%, the three-year survival rate was 54%, and the five-year survival rate was 28%. Median OS was 36.9 months in EGFR-mutated patients and 55.4 months in ALK-rearranged patients. The OS curve seemed to plateau after 72 months, and most of the patients who were still alive after more than five years are on treatment. Female sex, age under 75 years, an ECOG PS of 0 to 1, ALK rearrangement, postoperative recurrence, and presence of brain metastasis were significantly associated with longer OS. Conclusions A tail plateau was found in the survival curves of patients with advanced, EGFR-mutated and ALK-rearranged NSCLC, but most were on treatment, especially with EGFR-mutated NSCLC.