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Introduction: Cisplatin-based chemotherapy was established in the 1980s, and it has been improved by the development of a short hydration protocol in lung cancer therapy. However, cisplatin-based chemotherapy is still associated with renal toxicity. Because 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) is known to be a mitochondrial activator and a heme oxygenase-1 (HO-1) inducer, 5-ALA with SFC is speculated to mitigate cisplatin-induced renal inflammation. Methods: We investigated the effects of oral administration of 5-ALA with SFC for preventing cisplatin-based nephrotoxicity in patients with lung cancer and evaluated its benefits for patients who received cisplatin-based chemotherapy. The primary endpoint was the significance of the difference between the serum creatinine (sCr) levels of the patients administered 5-ALA with SFC and those given placebo after course 1 of chemotherapy. The difference in the estimated glomerular filtration rate (eGFR) between the two groups was also evaluated as the secondary endpoint. Results: The double-blind, randomized two-arm studies were conducted at 15 medical facilities in Japan; 54 male and 20 female patients with lung cancer who received cisplatin-based chemotherapy between the ages of 42 and 75 years were included in the study. The compliance rate was greater than 94% in the primary assessment and subsequent drug administration periods. All enrolled patients completed the four cycles of cisplatin-based chemotherapy with short hydration. The average level of sCr on day 22 of course 1 was 0.707 mg/dL in the group treated with 5-ALA and SFC and 0.735 mg/dL in the placebo group, respectively, and the sCr in the test group was significantly lower than that in the placebo group (p = 0.038). In addition, the eGFR was significantly higher in the SPP-003 group than in the placebo group up to day 1 of course 3 (84.66 and 75.68 mL/min/1.73 m2, respectively, p = 0.02) and kept better even after the last administration of the study drug (82.37 and 73.49 mL/min/1.73 m2, respectively, p = 0.013). Conclusions: The oral administration of 5-ALA with SFC is beneficial to patients undergoing cisplatin-based chemotherapy for lung cancer with short hydration. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) induced by anti‐programmed‐cell death‐1 (PD‐1) and anti‐PD‐ligand 1 (PD‐L1) is potentially life‐threatening and is a common reason of the discontinuation of therapy. In contrast, an enhancement in antitumor effects was reported in patients who developed immune‐related adverse events, including ILD. Although recent evidence suggests that radiologic patterns of ILD may reflect the severity of ILD and the antitumor immune responses to anti‐PD‐1/PD‐L1 therapies, the association between radiologic features and clinical outcomes remains unclear. Methods: Patients with advanced non‐small‐cell lung cancer who were treated with 1st to 3rd line anti‐PD‐1 therapy from January 2016 through October 2017 were identified at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. ILD was diagnosed by the treating physicians, and chest computed tomography scans were independently reviewed to assess the radiologic features of ILD. Results: A total of 231 patients who received anti‐PD‐1 therapy were enrolled. Thirty‐one patients (14%) developed ILD. Sixteen patients were classified as having ground glass opacities (GGO), 16 were classified as having cryptogenic organizing pneumonia (COP), and one was classified as having pneumonitis not otherwise specified. Patients with GGO had significantly worse overall survival time compared to patients with COP (7.8 months (95% CI: 2.2‐NE) versus not reached (95% CI: 13.2‐NE); P = 0.0175). Multivariate analysis of all 231 patients also revealed that PS = 1 and ≥2 and GGO were significant predictors of a worse overall survival. Conclusions: This study demonstrated that patients who developed GGO exhibited worse outcomes among non‐small‐cell lung cancer patients receiving anti‐PD‐1 therapies. [ABSTRACT FROM AUTHOR]

Background: The current randomized, double-blind, phase 2 study assessed the efficacy and safety profile of a single intravenous administration of fosnetupitant, a neurokinin 1 receptor antagonist prodrug, for the prevention of chemotherapy-induced nausea and vomiting in Japanese patients receiving cisplatin-based chemotherapy.Methods: Patients scheduled to receive cisplatin (at a dose of ≥70 mg/m2 )-based regimens were randomly assigned to receive fosnetupitant at a dose of 81 mg or 235 mg or placebo in combination with palonosetron at a dose of 0.75 mg and dexamethasone. The primary endpoint was complete response (CR; no vomiting and no rescue medication) during the overall phase (0-120 hours). The overall CR rate was compared between each dose of fosnetupitant and the placebo group adjusting for the stratification factors of sex and age class (age <55 years vs age ≥55 years). Safety was assessed, with special attention given to events that potentially were suggestive of infusion site reactions.Results: A total of 594 patients were randomized. Of these, 194 patients, 195 patients, and 195 patients, respectively, in the placebo and fosnetupitant 81-mg and 235-mg dose groups were evaluable for efficacy. The overall CR rate was 54.7% for the placebo group, 63.8% for the fosnetupitant 81-mg dose group (adjusted difference, 9.1%; 95% CI, -0.4% to 18.6% [P = .061]), and 76.8% for the fosnetupitant 235-mg dose group (adjusted difference, 22.0%; 97.5% CI, 11.7% to 32.3% [P < .001]). Safety profiles were comparable between the 3 groups. The incidence of infusion site reactions related to fosnetupitant was ≤1% in each dose group.Conclusions: Fosnetupitant at a dose of 235 mg provided superior prevention of chemotherapy-induced nausea and vomiting among patients receiving cisplatin-based chemotherapy compared with the control group, and with a satisfactory safety profile. [ABSTRACT FROM AUTHOR]

Background: Although the clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in EGFR‐mutant non‐small cell lung cancer (NSCLC) patients has been demonstrated, their efficacy in EGFR‐mutant NSCLCs with central nervous system (CNS) metastases and the role of radiotherapy remain unclear. This study aimed to determine if it is preferable to add upfront cranial radiotherapy to EGFR‐TKIs in patients with EGFR‐mutant NSCLC with newly diagnosed brain metastases. Methods: We retrospectively analyzed the data of EGFR‐mutant NSCLC patients with CNS metastases who received EGFR‐TKIs as a first‐line therapy. Results: A total of 104 patients were enrolled and 39 patients received upfront brain radiotherapy, while 65 patients received first and second generation EGFR‐TKIs first. The median time to treatment failure (TTF) was 7.8 months (95% confidence interval [CI]: 6.3–9.4). The median survival time (MST) was 24.0 months (95% CI: 20.1–30.1). The overall response rate of the CNS was 37%. The median CNS progression‐free survival (PFS) was 13.2 months (95% CI: 10.0–16.2). Brain radiotherapy prior to EGFR‐TKI prolonged TTF (11.2 vs. 6.8 months, P = 0.038) and tended to prolong CNS‐PFS (15.6 vs. 11.1 months, P = 0.096) but was not significantly associated with overall survival (MST 26.1 vs. 24.0 months, P = 0.525). Univariate and multivariate analyses indicated that poor performance status and the presence of extracranial metastases were poor prognostic factors related to overall survival. Conclusion: EGFR‐TKI showed a favorable effect for EGFR‐mutant NSCLC patients with CNS metastases. Prolonged TTF and CNS‐PFS were observed with upfront brain radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced nausea and vomiting (CINV) are some of the most problematic symptoms for cancer patients. Triplet therapy consisting of a 5HT3 receptor antagonist, aprepitant, and dexamethasone is a guideline-recommended antiemetic prophylaxis for highly emetogenic chemotherapy (HEC). The efficacy and safety of triplet therapy using a 0.75-mg dose of palonosetron have not yet been investigated. We performed a prospective phase II study using triplet antiemetic therapy with 0.75 mg of palonosetron. Methods: Chemotherapy-naïve lung cancer patients scheduled to receive HEC were enrolled. The eligible patients were pretreated with antiemetic therapy consisting of the intravenous administration of 0.75 mg of palonosetron, and 9.9 mg of dexamethasone and the oral administration of 125 mg of aprepitant on day 1, followed by the oral administration of 80 mg of aprepitant on days 2-3 and the oral administration of 8 mg of dexamethasone on days 2-4. The primary endpoint was the complete response rate (the CR rate; no vomiting and no rescue medication) during the overall phase (0-120 h). Results: The efficacy analysis was performed in 63 patients. The CR rates during the overall, acute and delayed phases were 81.0, 96.8, and 81.0 %, respectively. The no nausea and no significant nausea rate during the overall phase were 54.0 and 66.7 %, respectively. The most common adverse event was grade 1 or 2 constipation. Conclusions: Triplet antiemetic therapy using a 0.75-mg dose of palonosetron shows a promising antiemetic effect in preventing CINV in lung cancer patients receiving HEC. [ABSTRACT FROM AUTHOR]

Recent studies have reported that immune-checkpoint inhibitors (ICIs) cause various immune-related adverse events (irAEs) and irAEs are associated with antitumor effects of ICIs. However, it remains unclear whether the incidence of irAEs was associated with types of PD-1 inhibitors and treatment lines. We retrospectively evaluated data of advanced or recurrent NSCLC patients treated in 1st to 3rd line with PD-1 inhibitors at Niigata Lung Cancer Treatment Group between January 2016 and October 2017. Of 231 patients who received anti-PD-1 therapies, 176 patients received nivolumab and 55 patients received pembrolizumab, and 63 patients (36%) developed irAEs in nivolumab therapy and 30 patients (55%) developed irAEs in pembrolizumab therapy. In the univariate analysis, male (Odd Ratio: OR 2.38, p = 0.01), smoker (OR 3.29, p = 0.002), squamous cell carcinoma (OR 2.99, p = 0.0001), pembrolizumab therapy (OR 2.15, p = 0.01), 1st line anti-PD-1 treatment (OR 2.07, p = 0.04), EGFR gene mutation negative (OR 8.77, p = 0.03) were significant predictors of irAEs. Multivariate analysis identified younger age (<75) (OR 2.46, p = 0.02), squamous cell carcinoma (OR 2.94, p = 0.0006) as independent positive predictors of irAEs. In patients treated with nivolumab, irAEs were associated with better survival (not reached vs. 15.4 months, p < 0.0005); however, in patients treated with pembrolizumab, irAEs were not correlated with overall survival (20 months vs. not reached p = 0.338). MST in patients with steroid treatment was significantly shorter than that in those without steroid treatment (not reached vs. 20.6 months, p < 0.01). The proportion of patients who received systemic steroid therapy for irAEs was not significantly different between nivolumab and pembrolizumab (46.0% vs. 46.6%, p = 0.954). In the current study, pembrolizumab therapy and 1st line treatment were predictors of irAE onset in univariate analysis, but not in multivariate analysis. [ABSTRACT FROM AUTHOR]

Background Recent studies have reported that immune-checkpoint inhibitors (ICIs) cause various immune-related adverse events (irAEs) and irAEs are associated with antitumor effects of ICIs. However, it remains unclear whether the incidence of irAEs was associated with types of PD-1 inhibitors and treatment lines. Methods We retrospectively evaluated data of advanced or recurrent NSCLC patients treated in 1st to 3rd line with PD-1 inhibitors at Niigata Lung Cancer Treatment Group between January 2016 and October 2017. Results Of 231 patients who received anti-PD-1 therapies, 176 patients received nivolumab and 55 patients received pembrolizumab, and 63 patients (36%) developed irAEs in nivolumab therapy and 30 patients (55%) developed irAEs in pembrolizumab therapy. In the univariate analysis, male (Odd Ratio: OR 2.38, p = 0.01), smoker (OR 3.29, p = 0.002), squamous cell carcinoma (OR 2.99, p = 0.0001), pembrolizumab therapy (OR 2.15, p = 0.01), 1st line anti-PD-1 treatment (OR 2.07, p = 0.04), EGFR gene mutation negative (OR 8.77, p = 0.03) were significant predictors of irAEs. Multivariate analysis identified younger age (<75) (OR 2.46, p = 0.02), squamous cell carcinoma (OR 2.94, p = 0.0006) as independent positive predictors of irAEs. In patients treated with nivolumab, irAEs were associated with better survival (not reached vs. 15.4 months, p < 0.0005); however, in patients treated with pembrolizumab, irAEs were not correlated with overall survival (20 months vs. not reached p = 0.338). MST in patients with steroid treatment was significantly shorter than that in those without steroid treatment (not reached vs. 20.6 months, p < 0.01). The proportion of patients who received systemic steroid therapy for irAEs was not significantly different between nivolumab and pembrolizumab (46.0% vs. 46.6%, p = 0.954). Conclusion In the current study, pembrolizumab therapy and 1st line treatment were predictors of irAE onset in univariate analysis, but not in multivariate analysis. [ABSTRACT FROM AUTHOR]