Real-world outcomes of nivolumab plus ipilimumab and pembrolizumab with platinum-based chemotherapy in advanced non-small cell lung cancer: a multicenter retrospective comparative study.

INTRODUCTION: Nivolumab plus ipilimumab with chemotherapy (NICT) and pembrolizumab with chemotherapy (PCT) are commonly used in patients with advanced non-small cell lung cancer (NSCLC). Compared with immune checkpoint inhibitor (ICI) monotherapy, ICI combination therapy can increase immune-related toxicity instead of prolonging survival. This study aimed to compare the efficacy and safety of NICT and PCT to decide on the favorable treatment. METHODS: We conducted a multi-center retrospective cohort study on patients who underwent NICT or PCT between December 2018 and May 2022. Propensity score matching (PSM) was performed with the variables age, sex, smoking status, performance status, stage, histology, and programmed cell death ligand-1 (PD-L1). The Kaplan-Meier method was used to compare survival for the matched patients. RESULTS: Six hundred consecutive patients were included. After PSM, 81 and 162 patients were enrolled in the NICT and PCT groups, respectively. The baseline characteristics were well-balanced. The median progression-free survival was equivalent (11.6 vs. 7.4 months; P = 0.582); however, the median overall survival (OS) was significantly longer in the NICT group than in the PCT group (26.0 vs. 16.8 months; P = 0.005). Furthermore, OS was better in PD-L1-negative patients who underwent NICT than in those who underwent PCT (26.0 vs. 16.8 months; P = 0.045). Safety profiles did not differ significantly in terms of severe adverse event and treatment-related death rates (P = 0.560, and 0.722, respectively). CONCLUSIONS: Real-world data suggests that NICT could be a favorable treatment option compared with PCT for patients with advanced NSCLC. Further follow-up is needed to determine the long-term prognostic benefit.

[A Case of Cytomegalovirus Reactivation after Chemoradiotherapy for Esophageal Cancer].

An 80-year-old man visited our hospital because of abdominal distension and epigastralgia. He was diagnosed esophageal cancer(Mt, SCC, T3N0M0, Stage Ⅱ). Because he was elderly, he received chemoradiotherapy(CRT)with S-1. At 54 Gy/27 Fr, he was admitted to the hospital because of cough exacerbation, fever, and food intake loss. A chest and abdominal CT showed a pneumonia pattern. First, antibiotics were started for suspected bacterial pneumonia. Nevertheless, elevation of inflammatory reactions and continuous fever were observed. As interstitial pneumonia was suspected, we started to administer an injection of prednisolone 60 mg. His respiratory symptoms were improved. However, we observed that disseminated erythema of the trunk spread throughout the body and liver enzymes further increased. As blood examination revealed elevated CMV-IgG antibody and C7-HRP positive, we diagnosed cytomegalovirus(CMV)reactivation. Administration of ganciclovir improved liver damage and disseminated erythema. He discharged our hospital while the steroid dose was reduced and valganciclovir continued administrating. The therapeutic effect of esophageal cancer was partial response(PR). We are following his symptoms and CT scan while adjusting the steroid dose. This is a rare case of CMV reactivation due to immunosuppression caused by steroids therapy during CRT against esophageal cancer. We should be aware of CMV infection during CRT and steroid therapy.

[Subtotal Esophagectomy for Mediastinal Lymph Node Oligo-Recurrence of ALK-Positive Lung Adenocarcinoma - A Case Report].

The patient was a 54-year-old woman with anaplastic lymphoma kinase-positive stage III B lung cancer. She received 4 courses of carboplatin(CBDCA)plus paclitaxel(PTX)plus bevacizumab(Bev)chemotherapy and crizotinib. Chemotherapy reduced the size of the primary site and mediastinal lymphadenopathy; however, the right supraclavicular and subcarinal lymph nodes were enlarged again during crizotinib treatment. Because it was an oligo-recurrence, we performed radiotherapy for these lymph nodes and changed systemic chemotherapy to alectinib. After 16 months, the patient exhibited esophageal stenosis due to subcarinal lymphadenopathy. We performed a subtotal esophagectomy, which improved the quality of life, and she was continued on an oral treatment of alectinib. Therefore, we suggest that an invasive surgical treatment is useful for oligo-recurrence cases.

[A case of metastatic cancer of unknown primary origin that progressed rapidly after complete remission via second-line chemotherapy].

Leptomeningeal metastasis occurs in approximately 5% of patients with metastatic solid carcinomas, and it is often diagnosed in patients with breast cancer, lung cancer, malignant melanoma, and digestive cancer. Herein, we report a case of a metastatic cancer of unknown primary origin. The leptomeningeal metastasis progressed quite rapidly, and the patient died despite achieving complete remission via second-line chemotherapy.

Impact of Lymphopenia Recovery After Chemoradiotherapy on Durvalumab Consolidation Therapy in Stage III NSCLC.

Introduction: Durvalumab maintenance therapy after definitive concurrent chemoradiotherapy (CRT) is the standard treatment modality for stage III NSCLC. Although severe treatment-related lymphopenia (TRL) during CRT may impair the efficacy of subsequent durvalumab therapy, data on the effect of TRL recovery on consolidation durvalumab therapy are lacking. Methods: This retrospective study evaluated patients with unresectable stage III NSCLC treated with durvalumab after concurrent CRT. The patients were enrolled across nine institutes throughout Japan between August 2018 and March 2020. The effect of TRL recovery on survival was evaluated. The patients were divided into two groups on the basis of their lymphocyte recovery status: the recovery group involved patients who did not experience severe TRL or experienced TRL but exhibited lymphocyte count recovery at durvalumab initiation, and the nonrecovery group involved patients who experienced severe TRL and did not exhibit lymphocyte count recovery on durvalumab initiation. Results: Among the 151 patients evaluated, 41 (27%) and 110 (73%) patients were classified into the recovery and the nonrecovery groups, respectively. The nonrecovery group had significantly worse progression-free survival than the recovery group (21.9 mo versus not reached, p = 0.018). Recovery from TRL (p = 0.027) and high pre-CRT lymphocyte count (p = 0.028) independently influenced progression-free survival. Conclusions: Baseline lymphocyte count and recovery from TRL at the start of durvalumab therapy were predictive factors for survival outcomes in patients with NSCLC treated with durvalumab consolidation after concurrent CRT.

Pneumonitis During Durvalumab Consolidation Therapy Affects Survival in Stage III NSCLC.

Introduction: Durvalumab consolidation therapy is the standard of care after concurrent chemoradiotherapy (CRT) for stage III NSCLC. Immune-related pneumonitis during durvalumab treatment is potentially fatal; however, information is lacking regarding the impact of pneumonitis on patient survival. This study investigates the effect of pulmonary and nonpulmonary immune-related adverse events (irAEs) on the efficacy of durvalumab treatment in patients with stage III NSCLC. Methods: We retrospectively assessed 158 patients who received durvalumab after CRT at nine Japanese institutions between July 2018 and March 2020. Survival outcomes were compared between patients who developed pneumonitis with those who developed irAEs other than pneumonitis. Patients who survived for less than 3 months were excluded to reduce immortal time bias. Results: Among 158 evaluated patients, 76 (48%) experienced grade less than or equal to one irAEs, whereas 82 (52%) experienced grade greater than or equal to two irAEs. Among the patients with grade greater than or equal to two irAEs, those with grade greater than or equal to two pneumonitis (n = 55) were compared with those with grade greater than or equal to two irAEs other than pneumonitis (n = 27). Patients with grade greater than or equal to two pneumonitis exhibited a significantly worse overall survival than those with grade greater than or equal to two irAEs that excluded pneumonitis. Multivariate analysis revealed that grade greater than or equal to two pneumonitis (hazard ratio = 3.71; 95% confidence interval, 1.85-7.45; p < 0.001) and squamous histology (hazard ratio = 2.64; 95% confidence interval, 1.29-5.42; p = 0.008) were independently associated with worse overall survival. Conclusions: After minimizing immortal time bias, pneumonitis grade two or greater and squamous histology were poor prognostic factors in patients who received consolidation durvalumab after CRT.