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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.

Immune checkpoint inhibitor (ICI)-related myocarditis has been reported to appear in the early phase after ICI initiation. Herein, we report the case of a 78-year-old man with non-small cell lung cancer. Pembrolizumab was introduced as first-line therapy. After 9 months, second-line therapy, including bevacizumab, was initiated. After another 7 months, echocardiography showed diffuse left ventricular dysfunction. Based on the histopathologic examination of the myocardium, the patient was diagnosed with ICI-related myocarditis. Initiation of prednisolone therapy improved cardiac function. This case of late-onset ICI-related myocarditis illustrates that endomyocardial biopsy can be useful in the differential diagnosis of cancer-related left ventricular dysfunction. Résumé: Il a été rapporté qu’une myocardite pouvait survenir peu après l’instauration d’un traitement par des inhibiteurs des points de contrôle immunitaire (ICI). Nous présentons le cas d’un homme de 78 ans atteint d’un cancer du poumon non à petites cellules. Le pembrolizumab a été administré comme traitement de première intention. Neuf mois plus tard, un traitement de deuxième intention par le bévacizumab a été instauré. Après sept autres mois, l’échocardiographie a montré une dysfonction ventriculaire gauche diffuse. À la suite des résultats de l’examen histopathologique du myocarde, une myocardite liée aux ICI a été diagnostiquée. L’instauration d’un traitement par la prednisolone a amélioré la fonction cardiaque du patient. Ce cas de myocardite tardive liée aux ICI montre l’utilité éventuelle de la biopsie de l’endomyocarde dans le diagnostic différentiel d’une dysfonction ventriculaire gauche liée au cancer.

Introduction: Lorlatinib is an ALK tyrosine kinase inhibitor approved in Japan for the treatment of advanced ALK+ NSCLC. There has been little evidence about lorlatinib efficacy after first-line (1L) alectinib in clinical practice in Japan. Methods: We retrospectively analyzed patients with advanced ALK+ NSCLC previously treated with 1L alectinib at multiple sites in Japan. Primary objectives were to collect patient demographics at baseline and estimate time to treatment failure (TTF) with second-line (2L) or third-line (3L) or later line (≥3L) lorlatinib treatment. Secondary objectives included objective response rate (ORR) with lorlatinib, reason for discontinuation and time to last treatment failure with lorlatinib, TTF and ORR of alectinib, and combined TTF. Results: Among the 51 patients included in the study, 29 (56.9%) received 2L and 22 (43.1%) received ≥3L lorlatinib treatment. At lorlatinib initiation, brain metastases were reported in 25 patients (49.0%), and 32 (62.7%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Median TTF with lorlatinib was 11.1 months (95% confidence interval [CI]: 4.6–13.8) in any line, 10.8 months (95% CI: 3.9–13.8) in 2L, and 11.5 months (95% CI: 2.9–not reached) in ≥3L. Median TTF was 11.5 months (95% CI: 3.9–not reached) in patients with brain metastases at lorlatinib initiation and 9.9 months (95% CI: 4.3–13.8) in patients without brain metastases. ORR was 35.7% with any-line lorlatinib treatment. Conclusions: Patient characteristics and efficacy were comparable with previous reports when lorlatinib was given after 1L alectinib in patients with ALK+ 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.

The efficacy of sotorasib for patients with KRAS G12C-mutated lung cancer with poor performance status (PS) and active brain metastases remains unknown. Here, we present a case in which sotorasib was introduced as the third-line therapy for a patient whose PS worsened due to active multiple brain metastases and disseminated intravascular coagulation (DIC) caused by rapid tumor progression; a marked effect was observed. DIC and PS improved two weeks after the start of the administration, and multiple brain metastases disappeared. The effect lasted only approximately four months due to the development of a new liver metastasis, but sotorasib improved PS and the DIC status was reversed, allowing for further treatment. Sotorasib could be considered for introduction in patients with poor PS.

Immunochemotherapy is widely used as the primary treatment for advanced lung cancer and is currently being investigated in the perioperative setting. Immunochemotherapy can produce marked tumor shrinkage and long-term anticancer effects that are not achieved with conventional anticancer drugs. Herein, we present the cases of two patients with relatively large advanced primary lung squamous cell carcinomas located just below the pleura, who developed pleuritis immediately after the initiation of immunochemotherapy, probably owing to leakage of tumor contents after marked tumor shrinkage. Treatment of pleuritis necessitates discontinuation of chemotherapy, and special attention to secondary pleuritis may be required after initiation of immunochemotherapy in patients with lung tumors located just below the pleura.

Introduction: Malignant pleural effusion (MPE) is associated with poor treatment outcome in patients with NSCLC receiving immune checkpoint inhibitors (ICIs). ICIs and chemotherapy (ICI/Chemo) combination therapy is currently the standard therapy for NSCLC, and some ICI/Chemo regimens for nonsquamous (non-Sq) NSCLC contain bevacizumab (BEV), which is effective for controlling MPE and may enhance immune response. This study aimed to determine the optimal first-line treatment for this clinical population. Methods: We retrospectively enrolled consecutive patients with non-Sq NSCLC with MPE who received ICI/Chemo or pembrolizumab monotherapy. Treatment outcomes were analyzed in patients with programmed death-ligand 1 (PD-L1) tumor proportion score more than or equal to 50% who were administered ICI/Chemo or pembrolizumab monotherapy (PD-L1 high cohort) and in patients with any PD-L1 status, treated with ICI/Chemo with or without BEV (ICI/Chemo cohort). We used propensity score matching (PSM) to reduce bias. Results: PD-L1 high and ICI/Chemo cohorts included 143 and 139 patients, respectively. In PD-L1 high cohort, 37 patients received ICI/Chemo. With PSM, the median progression-free survival was significantly longer in the ICI/Chemo group than in the pembrolizumab group (11.1 versus 3.9 mo, respectively, p = 0.0409). In the ICI/Chemo cohort, 23 patients received BEV. With PSM, no significant difference occurred in median progression-free survival between BEV and non-BEV groups (6.1 versus 7.4 mo, p = 0.9610). Conclusion: ICI/Chemo seemed more effective than pembrolizumab monotherapy for patients with non-Sq NSCLC with MPE. Nevertheless, the synergistic effect of BEV with ICI/Chemo may be limited. Further studies are needed to clarify the key factor in the tumor-induced immunosuppression environment in these patients.

Abstract. Virtual automatic bronchoscopic navigation (VBN) systems to determine the route to peripheral pulmonary lesions (PPLs) in lung cancer can improve diagnostic biopsy yields. However, compared with VBN, drawing manual routes using computed tomography images, especially with oblique methods, can identify more routes. The Ziostation2 VBN system combines the benefits of these 2 methods; we evaluated this performance by comparing 3 different route-determining methods. We retrospectively collected data from 50 patients with PPLs measuring

Objectives: The purpose of this study was to assess osimertinib-associated cardiac adverse events (AEs) in a real-world setting, using a retrospective single-center cohort study in Japan. Background: Cases of osimertinib-associated cardiac AEs have been reported but remain poorly understood. Methods: A total of 123 cases of advanced non–small cell lung cancer (NSCLC) with confirmed EGFR mutations who received osimertinib monotherapy from 2014 to 2019 at the Osaka International Cancer Institute (Osaka, Japan) were evaluated. Cardiac AEs were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Changes in left ventricular ejection fraction (LVEF) and rates of cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a ≥10 % absolute decline in LVEF from baseline to a value of

Effective control of severe immune-related adverse events, including cytokine release syndrome (CRS), is essential for the success of immunotherapy. We present a case of a granulocyte colony-stimulating factor–producing pleomorphic lung carcinoma treated with nivolumab plus ipilimumab which developed CRS and severe immune-related pneumonitis. The effect of immunotherapy was heterogeneous; gastric metastasis was eliminated, but the pulmonary lesion had primary resistance. Steroid and tocilizumab were successful in controlling CRS, but additional infliximab was necessary to control pneumonitis. To control immune-related adverse events, it is important to choose immunosuppressive agents to the specific target organ and inflammatory cells.

A SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rapidly progressing subtype of lung cancer with a poor prognosis and causes early postoperative recurrence among operable patients. In this study, we present a case of SMARCA4-UT with vertebral and chest wall invasion that successfully underwent conversion surgery after treatment with atezolizumab in combination with bevacizumab, paclitaxel, and carboplatin. The surgical specimen comprised SMARCA4-deficient and SMARCA2-positive adenocarcinoma, confirming intratumor heterogeneity. Gene panel analysis revealed no substantial differences in mutant gene profiles among tumors and no differences in SMARCA2 mutations. Furthermore, no recurrence occurred for 9 months after surgery. Thus, this case illustrates the possibility of multidisciplinary treatment including neoadjuvant therapy with immunotherapy and conversion surgery for SMARCA4-UT.