Search

Background: In Japan, over 25% of the population is elderly. As the risk of lung cancer increases with age, the number of elderly patients with lung cancer also increases. Given the challenges of an aging society, it is critical that elderly patients receive safe therapies., Aim: We assessed the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) aged ≥80 years., Methods: We retrospectively reviewed NSCLC patients aged ≥80 years old who received ICIs in the National Hospital Organization Kyoto Medical Center. We collected data on patient characteristics, prior treatments, number of cycles, response, and immune-related adverse events (irAEs) during ICI monotherapy., Results: A total of 45 patients were reviewed. The patients' median age was 85 years. Twenty-one, 17, and 7 patients received nivolumab, pembrolizumab, and atezolizumab, respectively. The disease control rate (partial response [PR] + stable disease [SD]) was 60.0%, and the progression-free survival was 3.4 months. In patients with nivolumab, seven patients (33.3%) achieved SD, and three patients (14.2%) achieved PR. In patients treated with pembrolizumab, seven patients (41.2%) achieved SD, and six patients (35.3%) achieved PR. In patients with atezolizumab, three patients (42.9%) achieved SD, and one patient (14.2%) achieved PR. Sixteen (36%) patients presented with a poor performance status. Three patients treated with pembrolizumab experienced grade 3 pneumonia, while one patient treated with nivolumab experienced grade 5 pneumonia., Conclusion: This study suggested that ICIs are an acceptable treatment option for NSCLC patients aged ≥80 years. Oncologists should pay attention to severe irAEs., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Simple Summary: This study aimed to assess the 3-year time to relapse (TTR) and overall survival (OS) of melanoma, including acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or the combination of dabrafenib and trametinib. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). This study suggests that both acral and mucosal types in the adjuvant setting are less effective than non-acral cutaneous melanoma at the 3-year TTR. Background: Adjuvant therapy has improved the clinical prognosis for postoperative melanoma patients. However, the long-term efficacy of this therapy on the melanoma acral and mucosal subtypes has not been fully evaluated in previous trials. This study assessed the 3-year recurrence-free survival and overall survival of patients with melanoma, including the acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or with the combination of the BRAF and MEK inhibitors dabrafenib and trametinib. Methods: We retrospectively analyzed both the 3-year time to relapse (TTR) and overall survival (OS) of 120 patients treated with anti-PD-1 antibody (Ab), or with the combination of dabrafenib and trametinib. Results: The overall median TTR was 18.4 months, with a range of 0.69 to 36 months. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. Baseline tumor thickness (TT) and acral type were associated with the TTR in subgroup analysis. Moreover, we classified 104 acral and non-acral cutaneous patients into the anti-PD-1 Abs or dabrafenib plus trametinib combined therapies cohort in multiple analyses. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). Conclusion: This study suggests that adjuvant therapy is more effective with non-acral cutaneous melanoma than either the acral or mucosal types at the 3-year TTR endpoint. [ABSTRACT FROM AUTHOR]

Background: A synergistic effect of cyclooxygenase inhibitors (COX‐I) and immune checkpoint inhibitors (ICIs) has been suggested. However, the impact of COX‐I on the efficacy of ICIs is unclear. Here, we aimed to evaluate the relationship between COX‐I use and the efficacy of ICI in patients with non‐small cell lung cancer (NSCLC). Methods: We retrospectively reviewed NSCLC patients who received ICI monotherapy. We defined COX‐I use as regular use of COX‐I other than low‐dose aspirin during the initiation of ICIs to the first evaluation of efficacy. The efficacy of ICIs was evaluated with response rate (RR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Differences in baseline characteristics by COX‐I use were controlled by using an inverse probability of treatment weighting (IPW) adjusted analysis. Results: A total of 198 patients with NSCLC received ICIs; 128, 50, and 20 patients received nivolumab, pembrolizumab, and atezolizumab, respectively; there were 65 (32.8%) COX‐I users. While there was no significant difference in RR (15.4% vs. 13.5%; p = 0.828), DCR (41.5% vs. 49.6%; p = 0.294), PFS (median, 2.69 vs. 3.68 months; 95% confidence intervals [CI], 1.77–5.19 vs. 2.20–4.60 months; p = 0.630), COX‐I users had significantly shorter OS than non‐COX‐I users (median, 6.08 vs. 16.10 months; 95% CI: 3.78–11.66 vs. 9.49–19.68 months; p = 0.003). On IPW adjusted analysis, there was no significant difference in OS (median, 7.85 vs. 15.11 months; 95% CI: 5.03–14.92 vs. 9.49–19.32 months; p = 0.081). Conclusions: There was no additional or negative impact of COX‐I use on the efficacy of ICIs in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Over the past two decades, antiresorptive agent‐related osteonecrosis of the jaw (ARONJ) has become a growing concern. We examined the incidence of ARONJ and identified its risk factors in lung cancer patients in the real‐world clinical setting. To our knowledge, we are the first to do so. Patients and methods: We retrospectively analyzed lung cancer patients with bone metastases who had received anti‐resorptive agents (zoledronate or denosumab) at the National Hospital Organization Kyoto Medical Center from October 2012 to September 2018. All ARONJ cases were diagnosed by the dentists according to the established diagnostic criteria. Results: A total of 171 patients were reviewed, 13 (7.6%) of whom experienced ARONJ. Among the 13 patients, six (46.2%), four (30.8%) and three (23.1%) had adenocarcinoma, squamous carcinoma and not otherwise specified, respectively. ARONJ was stage 2 in three (23.1%) patients and stage 3 in 10 (76.9%). More cycles of antiresorptive agents (odds ratio [OR] = 11.54; 95% confidence interval [CI], 2.47–53.99; P < 0.01), use of immune checkpoint inhibitors (ICIs; OR = 5.05; 95% CI, 1.56–16.37; P < 0.01) and longer survival duration (≥2 years; OR = 12.16; 95% CI, 3.17–46.65; P < 0.01) were independently associated with ARONJ in a multivariate analysis. Conclusions: The incidence of ARONJ was relatively high in lung cancer patients with bone metastases. When using antiresorptive agents, oncologists should closely monitor patients for ARONJ during the course of treatment and regularly consult with dentists, especially in patients receiving ICIs. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the efficacy and safety of retreatment with anti‐programmed death 1 (anti‐PD‐1) antibodies in patients with advanced non‐small cell lung cancer (NSCLC) after prior treatment with anti‐programmed death‐ligand 1 (anti‐PD‐L1) antibodies. Methods: Data (N = 15) on patients' characteristics, number of cycles, regimens, their best response and immune‐related adverse events (irAEs) were recorded retrospectively. Results: NSCLC was initially treated with anti‐PD‐L1 antibody atezolizumab (N = 14) or durvalumab (N = 1). No patients had a high (≥50%) tumor expression of PD‐L1. The median cycles for atezolizumab were five (range 1–15), and median progression‐free survival was 2.8 and 6.0 months for atezolizumab and durvalumab, respectively. Five (33.3%) and nine (60.0%) patients showed stable and progressive disease as their best response, respectively. No differences in irAEs between anti‐PD‐L1 and anti‐PD‐1 antibodies occurred. Conclusion: Patients treated with anti‐PD‐L1 antibodies for NSCLC received limited benefits from retreatment with anti‐PD‐1 antibodies. [ABSTRACT FROM AUTHOR]

Although it ameliorates lung cancer, immunotherapy with immune checkpoint inhibitors (ICIs) presents complications of infectious diseases, including tuberculosis. Incidence of tuberculosis during immunotherapy remains unclear. We found that 1.7% of patients developed active tuberculosis during immunotherapy at our institution. In patients with a positive interferon-gamma release assay status before ICI therapy, physicians should pay close attention to developing tuberculosis. [ABSTRACT FROM AUTHOR]

There have been very few reports on the use of immune checkpoint inhibitors for malignant tumors during pregnancy. Herein, the current study reports a case of a patient diagnosed with advanced malignant melanoma who was treated with pembrolizumab during pregnancy. A 40-year-old primigravida underwent noninvasive prenatal testing at 10 weeks of gestation, and the result was inconclusive, suggesting the possibility of maternal malignancy. A biopsy of the gluteal mass led to a diagnosis of malignant melanoma, and computed tomography revealed extensive metastases in her lungs and lymph nodes. She had a strong desire to proceed with pregnancy. In consideration of fetal growth and maturation, monotherapy was administered with pembrolizumab from 21 weeks of gestation, aiming for 28 weeks of gestation. The fetus grew well without maternal complications. At 28 weeks of pregnancy, the patient gave birth to a healthy boy by cesarean section. There was no evidence of metastasis in the placenta. The patient received nivolumab-ipilimumab combination therapy from postpartum day 13, followed by nivolumab monotherapy, and has been alive with controlled disease for 20 months. [ABSTRACT FROM AUTHOR]

Immunotherapy with immune checkpoint inhibitors (ICIs), while ameliorating lung cancer, can cause infectious diseases, including tuberculosis, in addition to immune-related noninfectious complications. In the clinical setting, the efficacy of ICIs to treat mycobacterial infection remains controversial. We report 3 cases of acute Mycobacterium avium complex lung disease during immunotherapy with ICIs. [ABSTRACT FROM AUTHOR]

As most clinical trials evaluating BRAF and MEK inhibitor combination therapy (B + Minh) have been conducted in Western countries, little is known about the effect of B + Minh among East Asian populations. Data from patients with advanced melanoma treated using B + Minh (either dabrafenib + trametinib or encorafenib + binimetinib) were retrospectively collected from 16 institutes in Japan. Response rates, adverse events, patterns of failure and survival were analysed. We analysed 112 of 144 collected patient records and, of these, 14 had acral/mucosal melanoma. The response rate for the entire cohort was 75.0%. There were no statistical differences in response rates between acral/mucosal and cutaneous melanomas (64.3% versus 76.5%), whereas previous treatment using immune checkpoint inhibitors (ICIs) did not affect response (72.7% versus 73.9%) to B + Minh, response to ICI after B + Minh was only 20%. Patients who achieved complete response had the best overall survival rates at 24 months (94.7%). Elevated serum lactate dehydrogenase levels and 3 or more metastatic sites were independently associated with survival. The most common relapse site was the brain (17.9%). More than half of the patients (58.8%) experienced grade III/IV pyrexia. B + Minh was effective among Japanese patients with melanoma, including those with acral/mucosal melanoma. Factors associated with survival were similar to previous Western studies. B + Minh response was not affected by the previous use of ICI; however, vigilance against brain metastasis during B + Minh therapy is required as the brain was our most commonly encountered relapse site. • The proportion of BRAF mutations greatly correlate with clinical type. • Little is known about the effect of BRAF/MEK inhibitors among Asian populations. • BRAF/MEK inhibitors were effective among Asians including acral/mucosal melanoma. • Factors associated with survival were similar to previous western studies. • Brain was our most commonly encountered relapse site in our study cohort. [ABSTRACT FROM AUTHOR]