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2545 Background: Patients treated with programmed cell death 1 (PD-1)-blockade therapy fall into 3 distinct subgroups: non-responders presenting early disease progression, long survivors who achieve durable disease control, and the remaining short-term responders. We reported that the prediction formula comprised of the percentages of CD62L-downregulated (CD62Llow) and CD25+FOXP3+CD4+T cells in the peripheral blood predicted non-responders of non-small cell lung cancer patients (n = 50) scheduled to receive anti-PD-1-antibody (nivolumab) therapy in the 2017 ASCO meeting. In this study, we included 171 patients with NSCLC who were scheduled for nivolumab treatment after obtaining written informed consent. Peripheral blood mononuclear cells (PBMC) were examined before and after Nivolumab therapy up to 2 years to investigate the differences between long survivors and short-term responders. Methods: The patients received Nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks. Tumor response was assessed with the use of the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, at week 8 and every 8 weeks thereafter. PBMCs were analyzed with a 18-color microfluorometer, LSR Fortessa and a masscytometer, CyTOF. Results: The responder-type patient group whose prediction formula values were greater than 192 showed significantly longer PFS ( P< 0.0001) and OS ( P< 0.0001). The long survivors who consisted of tail plateau of PFS exhibited significantly more CD62LlowCD4+T cells than the short-term responders as pre-existing immunity. The remaining responders kept significantly higher percentages of CD62LlowCD4+T cells ( P= 0.0088) and prediction formula values ( P= 0.017) than the patients with acquired resistance. Conclusions: The pre-existing CD4+T cell balance between primed effector and regulatory T cells correlated with anti-PD-1 therapy response. Further, CD62Llowcell-dominant CD4+T cell immunity was required to maintain durable antitumor reactivity induced by anti-PD-1 antibody therapy. These results have important clinical implication, as they support anti-PD-1 therapy provision to all potentially responding patients and pave the way for new treatment strategies for patients with distinct CD4+T cell immune statuses. Clinical trial information: UMIN000020719.

9006Background: Development of treatment for EGFR-mutated non-small-cell lung cancer (NSCLC) had been focused on monotherapy of gefitinib, erlotinib, or afatinib. Combinations of EGFR-TKIs and VEGF inhibitors are one of candidates for next strategy for EGFR-mutated tumor. We conducted a phase III study comparing BE to E. Methods: Chemotherapy-naive pts with advanced non-squamous NSCLC harbouring EGFR-mutation were randomly assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). Status of EGFR mutations in plasma samples were monitored routinely during the study treatment and a second-line treatment. The primary endpoint was PFS. Secondary endpoints were OS, RR, safety, and QoL. We hypothesized that hazard ratio of PFS was 0.63. It was estimated that 147 events would be needed for the study to have a power of 80% and a two-sided significance level of 5%. Accordingly, this study was planned to enroll 214 pts in total. Results: Betw...

e21018Background: Antibody blockade of programmed death (PD)-1 has led to significant prolongation of overall survival in metastatic cancers, including non-small cell lung cancer (NSCLC). However, ...

Afatinib is an epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI). In a randomized phase III study(Lux- Lung 3 study)employing patients harboring EGFR mutations, patients administered afatinib show a significantly longer progression free survival time(PFS)than those administeredcombination chemotherapy comprising cisplatin andpemetrexed . However, most of the patients(95.2%)treatedwith afatinib experiencedd iarrhea. In the present report, 16 patients with EGFR mutations were treatedby afatinib at our institution from May 2014 to December 2014. Twelve patients were administered a diarrhea prevention herbal medicine, Hange-shashin-to. Seven of 12 patients(58%)had no diarrhea during the 28 days of therapy. All 4 of the patients who did not receive Hange-shashin-to experienced diarrhea above Grade 1 within 6 days of starting therapy. The rate of diarrhea differed significantly between the patients receiving and not receiving Hangeshashin- to. In conclusion, preventive administration of Hange-shashin-to may reduce the occurrence of diarrhea during afatinib treatment.

Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without specific treatments. Although the efficacy of intravenous immunoglobulin (IVIG) therapy for autoimmune diseases has been reported, that for IPF remains unknown. This study aims to determine the efficacy and safety of IVIG for IPF.In an exploratory, multicenter, non-randomized and prospective trial, patients with progressive IPF were enrolled. Patients were treated with IVIG for five consecutive days (5-day IVIG) or once monthly for five consecutive months (5-month IVIG). Changes in the vital capacity (VC), diffusion capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT) and high-resolution computed tomography (HRCT) findings were evaluated.A total of 10 patients with IPF were treated with IVIG: 6 were in 5-day IVIG and 4 were in 5-month IVIG group. In 5-day IVIG group, the treatment effects were temporal, and physiological and HRCT findings deteriorated in three of six patients. In 5-month IVIG group, changes in %VC, %DLCO and walk distance in 6MWT at 6 months were -0.9 ± 5.3%, 6.9 ± 12.6% and 79 ± 58 m (mean ± standard deviation), respectively, and the treatment effects were long lasting. The change in VC 6 months after starting IVIG was smaller than that of 6-12 months after starting IVIG (after cessation of IVIG) (-0.02 ± 0.15 vs -0.33 ± 0.14 L, P = 0.022). Ground glass opacities were diminished in two of four patients. Adverse events were mild and tolerable.This preliminary study shows that once-monthly IVIG treatment may be effective and tolerable in patients with IPF.

Erlotinib is a potent drug used for treating epidermal growth factor receptor (EGFR) mutation positive lung cancer. In this study, we report a case of erlotinib induced cutaneous vasculitis. The patient was a 69-year-old woman with a history of left lower lobe resection for lung cancer. Two years after the resection, she had metastasis in the adrenal glands for which we initiated erlotinib therapy at a dose of 150 mg/day. The patient developed multiple purpurae with a partially necrotic region on both lower thighs at 8 weeks after initiating therapy. The skin biopsy results revealed cutaneous vasculitis. We stopped erlotinib therapy after this diagnosis because of this adverse effect as well as because it exacerbated the cancer. The patient's skin manifestation disappeared 2 weeks after stopping therapy, with no recurrence of any symptoms of systemic vasculitis. We reviewed the literature on drug-induced vasculitis due to oral EGFR inhibitors and found 13 such cases. In most cases, the symptoms appeared 1-2 months after initiating therapy. In all the cases, the symptoms resolved within 2-6 weeks after stopping drug therapy. Erlotinib-induced cutaneous vasculitis is rare but may cause fatal systemic vasculitis. Therefore, the skin of patients who are undergoing erlotinib therapy should be carefully examined at regular intervals during the course of therapy for drug-induced adverse effects.

e19583 Background: PF is commonly concomitant disorder with lung cancer. Because PF sometimes deteriorates and results unfavorable clinical course, patients with PF are excluded from most cancer clinical trials. S-1 is a novel active oral fluoropyrimidine anticancer agent consisting of tegafur, gimeracil and oteracil potassium. Although most anti-cancer agent have pulmonary toxicity, post marketing surveillance reported S-1 has lower pulmonary toxicity incidence. We have conducted feasibility study of S-1 and carboplatin combination for patients with advanced or ineligible for other treatment modality of NSCLC patients. Methods: Patients with histologically or cytologically confirmed NSCLC, clinically diagnosed pulmonary fibrosis, aged 80 years old or younger, performance status 0-2 and chemo naive were eligible for the study. Carboplatin (AUC 5) was administered on day 1 and S-1 (80mg/m2/day) on day 1 to 14 for four to six cycles. Endpoints were response rate, common safety profiles and effect to PF. Results: From March 2009 to December 2011, 21 pts (19 males/ 2 females, median age 67 years old, ranged 55 to 77, 10 adenocarcinoma, 10 squamous, 1 adenosquamous, stage IIA: 1, IIIA: 3, IIIB: 9, IV: 4, recurrence: 4) were enrolled. All patients had moderate or severe PF. Treatment delivery; 1 cycle: 3pts, 2: 3pts, 3: 3pts, 4: 10pts, 5; 1pts, 6: 1pts. Partial responses were observed in 7 patients (RR; 33%). The median progression free survival duration was 4.0 months and the median overall survival duration in 10.4 months. During the treatment, 2 patient experienced moderate deterioration of pulmonary fibrosis, 1 experienced infectious pneumonia, all three patients recovered from the event. There was no treatment related death. Besides pulmonary toxicity, most common adverse events were myelotoxicities. Conclusions: This is the first trial of S-1 and carboplatin combination for patients with PF and NSCLC. The study revealed S-1 and carboplatin combination was feasible and active even in patients with PF and NSCLC who are usually excluded from cancer clinical trials.