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In Japan, microsatellite instability (MSI) testing for solid tumors was introduced in clinical practice in December 2018. Although immune checkpoint inhibitors (ICIs) are established standards of care for patients with MSI-high tumors, the status of implementing MSI testing in clinical practice remains unclear.We retrospectively reviewed the medical records of patients with solid tumors who underwent MSI testing between January 2019 and December 2020 at our institution.In total, 1,052 MSI tests were performed in 1,047 patients. Regardless of specimen volume and condition, the MSI status was successfully determined in 1,041 (99.0%) tests, encompassing 27 tumor types (microsatellite stable [MSS] or MSI-low: n = 991 [95.2%] and MSI-high: n = 50 [4.8%]). Patients whose specimens were fixed with 20% neutral buffered formalin (NBF) and who had specimens with prolonged storage (98.4% and 95.4%) showed lower success rates than those whose specimens were fixed with 10% NBF and who had specimens with nonprolonged storage (100.0% and 99.6%), respectively. The prolonged turnaround time (TAT) in MSI-high cases (median TAT: 24 days) was a critical issue that directly resulted in treatment delay. Of the 50 patients with MSI-high tumors, 24 (48.0%) received ICIs and 34 (68.0%) were referred to the Department of Clinical Genetic Oncology where 6 (12.0%) patients were diagnosed with Lynch syndrome.MSI testing was successfully performed for various types of tumors and specimens in clinical practice. Our study results identified certain issues associated with the clinical implementation of MSI testing, including optimal specimen selection, extended TAT in MSI-high cases, and awareness of hereditary tumors.

Neuroendocrine carcinoma (NEC) of the head and neck is a rare type of malignancy, accounting for only 0.3% of all head and neck cancers, and its clinicopathological and genomic features have not been fully characterized. We conducted a retrospective analysis of 27 patients with poorly differentiated NEC of the head and neck seen at our institution over a period of 15 years. Patient characteristics, adopted therapies, and clinical outcomes were reviewed based on the medical records. Pathological analysis and targeted sequencing of 523 cancer-related genes were performed using evaluable biopsied/resected specimens based on the clinical data. The most common tumor locations were the paranasal sinus (33%) and the oropharynx (19%). Eighty-one percent of the patients had locally advanced disease. The 3-year overall survival rates in all patients and in the 17 patients with locally advanced disease who received multimodal curative treatments were 39% and 53%, respectively. Histologically, large cell neuroendocrine carcinoma was the predominant subtype (58% of evaluable cases), and the Ki-67 labeling index ranged from 59 to 99% (median: 85%). Next-generation sequencing in 14 patients identified pathogenic/likely pathogenic variants in TP53, RB1, PIK3CA-related genes (PREX2, PIK3CA, and PTEN), NOTCH1, and SMARCA4 in six (43%), three (21%), two (14%), two (14%), and one (7%) patients, respectively. Sequencing also detected the FGFR3-TACC3 fusion gene in one patient. The median value of the total mutational burden (TMB) was 7.1/Mb, and three patients had TMB ≥ 10. Regardless of the aggressive pathological features, our data revealed favorable clinical characteristics in the patients with locally advanced disease who received curative treatment. The lower TP53 and RB1 mutation prevalence rates compared to those described for small cell lung cancer suggests the biological heterogeneity of NEC in different parts of the body. Furthermore, the FGFR3-TACC3 fusion gene and mutations in genes encoding the components of the NOTCH and PI3K/AKT/mTOR pathways found in our study may be promising targets for NEC of the head and neck.

Naomi Hayashi,1 Yasuyoshi Sato,1 Yu Fujiwara,1,2 Naoki Fukuda,1 Xiaofei Wang,1 Kenji Nakano,1 Testuya Urasaki,1 Akihiro Ohmoto,1 Makiko Ono,1 Junichi Tomomatsu,1 Yukiko Sato,3 Hiroki Mitani,4 Takashi Toshiyasu,5 Shunji Takahashi1 1Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 2Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York City, NY, USA; 3Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 4Head and Neck Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 5Radiation Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, JapanCorrespondence: Yasuyoshi SatoThe Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, JapanTel +8135200111Fax +81335200141Email yasuyoshi.sato@jfcr.or.jpPurpose: There have been few reports on the evaluation of cancer cachexia based on skeletal muscle mass index (SMI) in patients with head and neck cancer.Patients and Methods: One hundred and ninety-two head and neck cancer patients were enrolled. In definitive and adjuvant chemoradiotherapy settings, clinical outcomes were compared between cachexia and non-cachexia patients.Results: Forty patients were diagnosed with cachexia (20.8%). In the definitive setting, overall survival (OS) was significantly shorter in the cachexia group (3-year OS: 50.0% vs 88.5%; p < 0.01), and multivariate analysis identified UICC stage IV, baseline albumin of < 4 and cachexia as poor prognostic factors. However, cachexia was not significant in the adjuvant setting.Conclusion: Cancer cachexia was negatively associated with prognosis in patients with HNC who received definitive chemoradiotherapy. Nutritional intervention during chemoradiotherapy may improve survival in these patients.Keywords: head and neck cancer, squamous cell carcinoma of head and neck, sarcopenia, cachexia, muscle, skeletal, chemoradiotherapy, prognosis

Milademetan (DS‐3032, RAIN‐32) is an orally available mouse double minute 2 (MDM2) antagonist with potential antineoplastic activity owing to increase in p53 activity through interruption of the MDM2‐p53 interaction. This phase I, dose‐escalating study assessed the safety, tolerability, efficacy, and pharmacokinetics of milademetan in 18 Japanese patients with solid tumors who relapsed after or were refractory to standard therapy. Patients aged ≥ 20 years received oral milademetan once daily (60 mg, n = 3; 90 mg, n = 11; or 120 mg, n = 4) on days 1 to 21 in a 28‐day cycle. Dose‐limiting toxicities, safety, tolerability, maximum tolerated dose, pharmacokinetics, and recommended dose for phase II were determined. The most frequent treatment‐emergent adverse events included nausea (72.2%), decreased appetite (61.1%), platelet count decreased (61.1%), white blood cell count decreased (50.0%), fatigue (50.0%), and anemia (50.0%). Dose‐limiting toxicities (three events of platelet count decreased and one nausea) were observed in the 120‐mg cohort. The plasma concentrations of milademetan increased in a dose‐dependent manner. Stable disease was observed in seven out of 16 patients (43.8%). Milademetan was well tolerated and showed modest antitumor activity in Japanese patients with solid tumors. The recommended dose for phase II was considered to be 90 mg in the once‐daily 21/28‐day schedule. Future studies would be needed to further evaluate the potential safety, tolerability, and clinical activity of milademetan in patients with solid tumors and lymphomas. The trial was registered with Clinicaltrials.jp: JapicCTI‐142693., We are presenting the first report of a phase I study evaluating the safety, tolerability, efficacy, and pharmacokinetics of milademetan in Japanese patients with advanced solid tumors. The plasma concentrations of milademetan increased in a dose‐dependent manner. Milademetan was well tolerated and showed modest antitumor activity in Japanese patients with solid tumors.

BACKGROUND/AIM Lenvatinib is standard therapy for radioiodine-refractory differentiated thyroid cancer (RR-DTC), although the optimal timing for starting treatment is still controversial. The aim of this study was to evaluate the prognostic impact of baseline tumour size (BTS) in patients with RR-DTC treated with lenvatinib. PATIENTS AND METHODS Fifty-one RR-DTC patients who had at least one measurable lesion and treated with lenvatinib were retrospectively analysed. BTS was defined as the sum of the longest dimensions of all measurable target lesions. RESULTS Median progression-free survival (PFS) and overall survival (OS) in the larger BTS (≥42 mm) group were shorter than those in the smaller (

BACKGROUND Eribulin is widely used for the treatment of breast cancer and soft-tissue sarcoma (STS). Previous studies identified the pre-treatment absolute lymphocyte count, baseline neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein concentration as potential prognostic markers in patients with breast cancer treated with eribulin. However, prognostic factors for eribulin treatment in patients with STS have not been identified. PATIENTS AND METHODS This was a retrospective analysis of data collected prospectively from 53 patients who were treated with eribulin for recurrent or metastatic STS between March 2016 and August 2019. Univariate and multivariate analyses were performed to determine the predictive factors of durable clinical benefit, progression-free survival, and overall survival. RESULTS L-Sarcoma histology [hazard ratio (HR)=28.20, 95% confidence intervaI (CI)=1.67-476.00; p=0.021] and pre-treatment NLR

Background/aim In the CheckMate-141 trial regarding head and neck cancer (HNC), nivolumab conferred a survival benefit to patients. However, the best treatment sequence of chemotherapy and anti-PD-1/PD-L1 therapy in these cancers is unclear. Patients and methods This was an observational study using data collected prospectively from 97 HNC patients treated with nivolumab at our institutions. Twenty-two HNC patients who received paclitaxel-based chemotherapy before (pre-PTX, n=12) and after (post-PTX, n=10) nivolumab were evaluated. Results The median follow-up time was 15.9 months (range=6.9-35.9 months). There was a significant difference in the overall response rate (ORR) between pre-PTX (17%) and post-PTX (70%) (p=0.027). Similarly, time to progression (TTP) was significantly longer after nivolumab than before nivolumab (post-PTX, 7.4 months; pre-PTX, 4.9 months, p=0.020). Conclusion Paclitaxel-based chemotherapy had a better ORR and TTP after nivolumab than before nivolumab for HNC. The sequential administration of anti-PD-1 therapy followed by paclitaxel-based chemotherapy could be a better strategy for HNC.

Background: Large prospective studies of chemotherapy for metastatic or recurrent adenoid cystic carcinoma (ACC) of the head and neck are lacking due to the rarity of ACC. The aim of this study is to evaluate the efficacy of carboplatin plus paclitaxel toward ACC and perform an exploratory investigation of the prognostic factors to investigate the optimal strategy for metastatic or recurrent ACC.Methods: We retrospectively analyzed recurrent or metastatic ACC patients treated with carboplatin plus paclitaxel between April 2007 and September 2019 in our hospital. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated, and an exploratory analysis of the prognostic factors including tumor growth rate (TGR) was conducted.Results: A total of 26 ACC patients were enrolled. ORR and DCR were 11.5% and 76.9%; the median PFS and OS were 8.1 and 22.3 months, respectively. From the results of the multivariate analysis, higher (≥ 6%/month) TGR was associated with worse PFS (hazard ratio [HR] 7.00, 95%CI 1.34–36.53, p = 0.02) and OS (HR 29.33, 95%CI 3.38–254.80, p Conclusions: Carboplatin plus paclitaxel showed modest efficacy for recurrent or metastatic ACC patients. Watchful waiting may be optimal for ACC patients with lower TGR. Systemic chemotherapy should be considered when TGR increases during active surveillance.

Background In the CheckMate-141 trial, nivolumab conferred a survival benefit in patients with recurrent or metastatic refractory squamous cell carcinoma (SCC) head and neck cancer (HNC). Here, we examined the efficacy of nivolumab in patients with histological subtypes or primary sites of HNC not included in the CheckMate-141 trial. Methods This was a retrospective analysis of data collected prospectively from 97 patients who were treated with nivolumab for recurrent or metastatic HNC at our institution. The patients were assigned to three groups based on HNC primary site: 1) oral cavity, pharynx, and larynx, which were included in CheckMate-141 (n = 68), 2) nasopharynx (excluded in CheckMate-141, n = 7) and 3) other primary sites excluded in CheckMate-141 (n = 22) and assigned to two groups according to histological subtype: 1) SCC (included in CheckMate-141, n = 83) and 2) non-SCC (all sites excluded in CheckMate-141, n = 14). Survival outcomes and nivolumab treatment response were compared between the primary site and histological subgroups. Results The median number of nivolumab treatments was 7 cycles (range, 1-53 cycles) and the median follow-up time was 9.1 months (range, 0.66-33.0 months). There were no significant differences in response rates between the three primary site subgroups (CheckMate-141 sites 22%, nasopharynx 43%, others 18%; p=0) or the two histological subtype subgroups (SCC 25%, non-SCC 7%, p=0). Similarly, overall survival and progression-free survival were comparable for patients stratified by primary site or histological subtype. Conclusion No significant difference in response rates or survival outcomes was detected between nivolumab-treated HNC patients with primary sites and histological subtypes that were included versus excluded in the CheckMate-141 trial. These data provide a potential rationale for nivolumab therapy for all HNC patients in clinical practice.

Simple Summary Second-line systematic therapy options for soft-tissue sarcoma (STS) have remained unchanged for decades due to the rarity and various histological types associated with STS. Challenges with molecular-targeted treatments for STS led to the approval of pazopanib and its wide use for STS. However, predictive markers of pazopanib treatment for STS have not been identified. Baseline neutrophil-to-lymphocyte ratio (NLR) is known as a candidate biomarker for several cancers. In this retrospective study, we investigated the use of the NLR as a predictor for the efficacy and prognosis of pazopanib in patients with STS. Our findings could be useful for the development of biomarker-targeted therapies for STS. Abstract Pazopanib with trabectedin and eribulin is widely used to treat soft-tissue sarcoma (STS). We have shown that baseline neutrophil-to-lymphocyte ratio (NLR) may predict the efficacy and patient prognosis of eribulin. Changes in NLR, but not baseline NLR, can predict patient prognosis of trabectedin. However, prognostic factors of pazopanib for STS have not been identified. We present a retrospective analysis of 141 patients treated with pazopanib for recurrent or metastatic non-round cell STS. Univariate and multivariate analyses were performed to determine the predictive factors of durable clinical benefit (DCB), overall survival (OS), and progression-free survival. L-sarcoma histology (odds ratio [OR] = 0.31, 95% CI = 0.12–0.79; p = 0.014) and pre-treatment NLR < 3.0 (OR = 2.03, 95% CI = 1.02–6.67; p = 0.045) were independent predictive factors of DCB. Pre-treatment NLR < 3.0 (hazard ratio [HR] = 0.55, 95% CI = 0.36–0.84; p = 0.0057), liposarcoma histology (HR = 1.78, 95% CI = 1.09–2.91; p = 0.022), primary extremity site (HR = 0.48, 95% CI = 0.31–0.75; p = 0.0010), ECOG PS ≥ 1 (HR = 1.62, 95% CI = 1.08–2.42; p = 0.019), and CRP < 0.3 (HR = 0.52, 95% CI = 0.33–0.82; p = 0.0050) were independent predictive factors of OS. These findings indicate that baseline NLR predicts the efficacy and patient prognosis of pazopanib for STS.

Immune checkpoint inhibitors (ICIs) play a significant role in therapy for relapsed or refractory cancers due to their excellent efficacy. ICIs, however, frequently induce immune-related adverse events (irAEs) in various tissues and organs, sometimes leading to severe conditions. Thus, early identification and treatment of irAEs are important. Herein, the authors report two cases of a rare type of irAE, severe keratoconjunctivitis with deterioration of eyesight, induced by ICIs. Characteristically, both cases were accompanied by concurrent severe oral mucositis. The patients were treated successfully with both systemic and topical ophthalmic corticosteroids, resulting in complete remission of severe pseudomembranous conjunctivitis and full recovery of eyesight. ICI-induced keratoconjunctivitis progresses rapidly and can lead to blindness. Thus, prompt diagnosis and treatment are necessary.Lay abstract Currently, ‘immunotherapy’ has changed cancer treatments drastically. In this article, the authors use immune checkpoint inhibitors (ICIs) for cancer treatments as ‘immunotherapy’. Generally, cancer puts on the brakes to stop attacking itself via immune checkpoint molecules to survive. ICIs inhibit the mechanism, and patients battle their cancer by using their own activated lymphocytes. However, the activated lymphocytes can attack patients' own normal tissues and organs. ‘Immune-related adverse events’ can occur everywhere in the body. In this article, the authors present an ICI-related severe eye trouble, which is very rare but can put patients at risk of vision loss.

Background: The clinical benefit of systemic chemotherapy for recurrent/metastatic retroperitoneal/intra-abdominal soft tissue sarcoma (STS) compared to its benefits for other primary lesions has not been known or sufficiently evaluated. Methods and Patients: We retrospectively reviewed the cases of the STS patients who consulted a department of medical oncology in Tokyo between June 2011 and March 2018, and we extracted the cases of patients with primary sites at the retroperitoneum/intra-abdomen (cohort R) or extremities/trunk (cohort E) who received systemic chemotherapy in a recurrent/metastatic setting, comparing the cohorts’ characteristics, chemotherapy details, and prognoses. Results: Of all 337 STS patients, we enrolled 49 patients in cohort R and 75 patients in cohort E. Liposarcoma was more frequently observed in cohort R (51.0%) than cohort E (22.7%). The median chemotherapy treatment line was two lines (range: 1–6) in cohort R and three lines (range: 1–9) in cohort E. The doxorubicin usage rates differed in recurrent/metastatic settings (90.0% in cohort R and 55.0% in cohort E), due mainly to the higher rate of a perioperative chemotherapy treatment history in cohort E (52.0% vs. 6.1% in cohort R). The median overall survival from the start of salvage chemotherapy was 31.9 months (cohort R; 95% CI: 20.9–42.8) and 27.1 months (cohort E; 95% CI: 21.6–32.5) (p = 0.549). Conclusion: There were differences in the distributions of pathology and antitumor drugs used in a salvage setting between retroperitoneal/intra-abdominal and extremities/trunk STS patients in recurrent/metastatic settings, but the prognoses with salvage chemotherapy were similar in the two cohorts.

Objectives: This retrospective observational study is conducted to evaluate the association between cancer cachexia and prognosis in head and neck cancer patients treated with chemoradiotherapy using skeletal muscle mass index at the level of the third lumbar vertebra with computed tomography.Methods: Two hundred forty-two patients were enrolled and categorized into the following four groups based on cancer cachexia criteria and treatment setting: definitive chemoradiotherapy with cachexia, definitive chemoradiotherapy without cachexia, adjuvant chemoradiotherapy with cachexia, and adjuvant chemoradiotherapy without cachexia. Progression-free survival (PFS) and overall survival (OS) between cachexia and non-cachexia groups were compared by treatment setting using the long-rank test. Prognostic factors were evaluated using the Cox proportional hazards model.Results: Fifty patients were diagnosed with cancer cachexia (20.7%). In the definitive setting, both PFS and OS were significantly shorter in the cachexia group (median PFS, 15.5 months vs. not reached, p < 0.01; median OS, 48.4 months vs. not reached. p < 0.01). Conversely, there was no significant difference between the two groups in the adjuvant setting. UICC Stage IV, base of albumin of Conclusion: Cancer cachexia was negatively related with prognosis in patients with head and neck squamous cell carcinoma who received definitive chemoradiotherapy. Nutritional intervention during chemoradiotherapy may improve survival in these patients. Further research is warranted.

Background/Aim: Trabectedin is a synthetic antineoplastic agent approved for advanced soft tissue sarcoma (STS) in Japan. The aim of this study was to evaluate the efficacy and safety of the Japan-approved dose of trabectedin for advanced STS. Patients and Methods: We retrospectively reviewed 38 patients with advanced STS who received salvage chemotherapy with trabectedin. Results: The overall response and disease control rates were 16% (5 patients) and 67% (20 patients), respectively. The median progression-free and overall survival were 7.3 and 17.8 months, respectively. There were no significant differences between patients with liposarcoma or leiomyosarcoma and those without, or between patients with TRS and those without. The most common grade 3-4 AEs were elevated transaminases and neutropenia. Conclusion: Trabectedin 1.2 mg/m(2), as the approved dose in Japan, showed similar efficacy to the dose of 1.5 mg/m(2) used in Western countries. Trabectedin could be an option for advanced STS in Japan, regardless of histological subtype.

Cytotoxic chemotherapy, including cyclophosphamide, vincristine, and dacarbazine (CVD) therapy, is widely used to treat metastatic pheochromocytoma and paraganglioma. Because these diseases are rare, studies are needed to establish treatment strategies. This was a single-center and retrospective study to analyze the efficacy of chemotherapy for patients with metastatic pheochromocytoma and paraganglioma diagnosed in 1983-2020. Clinical characteristics, tumor volume response, biochemical response based on catecholamine level, overall survival, and progression-free survival were evaluated. Patients with a complete response or partial response in tumor volume or catecholamine level were classified as responders. Sixteen patients were administered chemotherapy for a median of 16.5 cycles (interquartile range, 10-42). The tumor volume response was classified as follows: partial response (N = 4), stable disease (N = 9), and progressive disease (N = 3) (disease control rate = 81%). The biochemical responses were as follows: complete response (N = 2), partial response (N = 5), no change (N = 3), and progressive disease (N = 1) (disease control rate = 91%). The 5-year survival rate was 50% (95% confidence interval [CI], 21-74%) and median overall survival was 4.4 years (95% CI, 2.4 years-not reached). Overall survival and progression-free survival between responders and nonresponders were not statistically different. One patient developed myelodysplastic syndrome during CVD therapy. In conclusion, chemotherapy achieved disease control among more than half of patients, although survival did not differ between responders and nonresponders. Further fundamental research and prospective trials are needed to analyze the efficacy of CVD therapy.

Background Head and neck squamous cell carcinoma (HNSCC) is a geriatric cancer. However, older adult patients are frequently underrepresented in large clinical trials. Aims The aim of this study is to assess the efficacy and safety of the EXTREME regimen (platinum + fluorouracil + cetuximab) in older and younger adult patients with HNSCC. Methods and results Patients with recurrent or metastatic HNSCC treated with the EXTREME regimen were retrospectively analyzed. We compare the efficacy and safety in older (aged ≥70 years) younger (aged

SummaryBackground This open-label, phase 1 study investigated TAS4464, a potent NEDD8-activating enzyme inhibitor, in patients with advanced/metastatic solid tumors (JapicCTI-173,488; registered 13/01/2017). The primary objective was dose-limiting toxicities (DLTs). Maximum-tolerated dose (MTD) was investigated using an accelerated titration design. Methods The starting 10-mg/m2 dose was followed by an initial accelerated stage (weekly dosing; n = 11). Based on liver function test (LFT) results, a 14-day, 20-mg/m2 dose lead-in period was implemented (weekly dosing with lead-in; n = 6). Results Abnormal LFT changes and gastrointestinal effects were the most common treatment-related adverse events (AEs). DLTs with 56-mg/m2 weekly dosing occurred in 1/5 patients; five patients had grade ≥ 2 abnormal LFT changes at 40- and 56-mg/m2 weekly doses. Further dose escalation ceased because of the possibility of severe abnormal LFT changes occurring. DLTs with weekly dosing with lead-in occurred in 1/5 patients at a 56-mg/m2 dose; MTD could not be determined because discontinuation criteria for additional enrollment at that particular dose level were met. As no further enrollment at lower doses occurred, dose escalation assessment was discontinued. Serious treatment-related AEs, AEs leading to treatment discontinuation, and DLTs were all related to abnormal LFT changes, suggesting that TAS4464 administration could affect liver function. This effect was dose-dependent but considered reversible. Complete or partial responses to TAS4464 were not observed; one patient achieved prolonged stable disease. Conclusions MTD could not be determined due to TAS4464 effects on liver function. Further evaluation of the mechanism of NEDD8-activating enzyme inhibitor-induced abnormal liver function is required. Trial registration number JapicCTI-173,488 (registered with Japan Pharmaceutical Information Center). Registration date 13 January 2017

Clinical evidence regarding eribulin treatment for patients with soft tissue sarcoma (STS) is limited to those with L-sarcoma (leiomyosarcoma and liposarcoma) who have completed at least two chemotherapies. Whether histological subtypes and treatment lines affect the efficacy and safety of eribulin for patients with STS has yet to be elucidated. The current study retrospectively reviewed patients with STS receiving eribulin at the Cancer Institute Hospital of JFCR and evaluated the prognostic factors affecting its efficacy and safety by histological diagnoses and treatment lines. A total of 41 patients with STS, including 26 with L-sarcoma, underwent eribulin treatment. Additionally, a total of and 14 patients, including 12 with L-sarcoma, received eribulin as a second-line treatment. The results revealed that patients with L-sarcoma demonstrated longer progression-free survival (PFS) rates compared with patients without L-sarcoma (4.5 vs. 2.3 months; P=0.005). Furthermore, differences in treatment line significantly affected PFS (4.5 months in second-line treatment vs. 2.4 months in later lines; P=0.037). A high number of patients with L-sarcoma received eribulin as a second-line treatment. Regarding safety, several adverse events were reported, such as neutropenia, which were more frequently observed in patients with L-sarcoma or other patients receiving eribulin as a second-line treatment. However, most adverse events were tolerable. The clinical efficacy of eribulin was increased in patients with L-sarcoma, which was similar to previous clinical trials. However, treatment lines could also affect its efficacy. When evaluating the clinical value of eribulin to STS, it is important to consider treatment lines.

Taselisib is a potent and selective phosphatidylinositide 3‐kinase (PI3K) inhibitor. The present article reports the first study of taselisib administration in Japanese patients. The aim of this 2‐stage, phase I, multicenter, open‐label, dose‐escalation study was to evaluate the safety, pharmacokinetics, and preliminary efficacy of taselisib as monotherapy in Japanese patients with advanced solid tumors (stage 1), and as part of combination therapy in Japanese patients with hormone receptor (HR)‐positive locally advanced or recurrent breast cancer (stage 2). In stage 1, oral taselisib tablets 2, 4, and 6 mg/d were given in 28‐day cycles. In stage 2, successive cohorts of patients received oral taselisib tablets (2 or 4 mg/d) with i.m. fulvestrant 500 mg. Nine and 6 patients were enrolled in stage 1 and stage 2, respectively. Taselisib was well tolerated. No dose‐limiting toxicities were experienced in any cohort of patients and no deaths were observed. The most common treatment‐related adverse events in stage 1 and stage 2, respectively, were rash (55.6%, 66.7%), diarrhea (44.4%, 66.7%), and stomatitis (44.4%, 66.7%). Taselisib was rapidly absorbed after dosage; its half‐life was 12.9‐32.0 hours in stage 1 and 16.1‐26.5 hours in stage 2. Two patients achieved partial response (PR), 5 patients had stable disease (SD) and 2 patients had progressive disease (PD) in stage 1, and 1 patient had PR and 3 patients had SD in stage 2. All patients with PR were positive for PIK3CA gene mutations. These preliminary data suggest that taselisib may be effective in patients with PIK3CA‐mutated solid tumors or HR‐positive advanced breast cancer.

Humoral hypercalcemia due to parathyroid hormone-related peptide (PTHrP) elevation is a well-known complication of various malignancies, but the situation is rare concerning hematological malignancies except for adult T-cell leukemia/lymphoma. We report a case of Richter’s syndrome with humoral hypercalcemia, and demonstrate by reverse transcription polymerase chain reaction (RT-PCR) that peripheral blood PTHrP levels were 2,500-fold higher compared to healthy controls. PTHrP production by tumor cells in chronic lymphocytic leukemia (CLL) and Richter’s syndrome has been previously demonstrated by nonquantitative methods such as immunohistochemistry and northern blot analysis, but this is the first report using the RT-PCR method. The presented case did not have hypercalcemia when initially diagnosed as small lymphocytic lymphoma (SLL), and as reported earlier, the development of hypercalcemia may be an indication of the transformation to Richter’s syndrome in patients with CLL/SLL.

Purpose Ipatasertib is a selective inhibitor of Akt, a frequently activated protein kinase in human cancers. The current study assessed the safety, tolerability, and pharmacokinetics of ipatasertib in Japanese patients with solid tumors. Methods This was a phase I, open-label, 3 + 3 dose-escalation study conducted in two stages. In stage I, Japanese patients with solid tumors were administered ipatasertib 200, 400, or 600 mg/day for 21 days of a 28-day cycle. In stage II, Japanese patients with castration-resistant prostate cancer were administered ipatasertib 200 or 400 mg/day in combination with abiraterone and prednisolone in 28-day cycles. Dose-limiting toxicity (DLT) was assessed at each dose before enrolling patients at a higher dose; DLT was used to determine the maximum tolerated dose (MTD) and maximum administered dose (MAD). Pharmacokinetic parameters were assessed after a single dose and at steady state. Results Fifteen patients were enrolled in Stage I and six in Stage II. The ipatasertib MTD was 600 mg as monotherapy and MAD was 400 mg in combination with abiraterone and prednisolone. Ipatasertib plasma exposure was dose proportional across the dose range, and was not markedly affected by concurrent administration of abiraterone plus prednisolone. Stable disease (SD) was observed in eight patients treated with ipatasertib monotherapy (53.3%); four patients had SD and one had complete response with ipatasertib plus abiraterone and prednisolone. Conclusions Ipatasertib, at the monotherapy MTD of 600 mg/day and MAD of 400 mg/day in combination with abiraterone and prednisolone, was safe and tolerable in Japanese patients with solid tumors. Electronic supplementary material The online version of this article (10.1007/s00280-019-03882-7) contains supplementary material, which is available to authorized users.

e18007 Background: Concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) is a standard treatment for locally advanced head and neck cancer (LAHNC) in the definitive setting. Three cycles of 100 mg/m2 CDDP for every three weeks (Q3W) are now recommended but compliance with CCRT is relatively low due to its severe toxicity. Therefore, the potential de-escalation strategies for LAHNC have been discussed to decrease the therapeutic toxicity. Methods: Patients with LAHNC who underwent definitive CCRT with CDDP between 2012 and 2018 at The Cancer Institute Hospital of Japanese Foundation for Cancer Research were analyzed. Patients were classified into two groups based on the planned CDDP dose: (A) 100 mg/m2 and (B) 80 mg/m2 Q3W for three times. One-to-one propensity score matching was performed to minimize bias between two groups. After patients in two groups were matched by using propensity score, the overall survival (OS), recurrence-free survival (RFS), local recurrence-free survival (LRFS), and metastatic recurrence-free survival (MRFS) were analyzed by the Kaplan-Meier method with the Cox proportional hazards model. The follow-up term was set as two years to evaluate the early survival benefit. The dose and density of CDDP and the objective adverse events were also assessed. Results: A total of 304 patients were included with the median age of 62 (Interquartile range [IQR]: 54-67) years. Among them, 249 patients (82%) were male. Patients were treated with 100 mg/m2 CDDP (n = 145) and 80 mg/m2 CDDP (n = 159) regimens. After the propensity score matching, 119 patients were included in each group, respectively. There were no significant differences in baseline characteristics between two propensity-matched cohorts. The median follow-up time was 24 months in each group. Two-year OS was 93.0% (95% confidence interval [CI]: 88.4-97.8) in group A and 94.9% (91.0-99.0) in group B. Two-year RFS was 86.5% (80.6-92.9) in group A and 83.1% (76.6-90.1) in group B, respectively. No significant difference was observed in OS (Hazard ratio [HR] = 1.42, 95% CI: 0.49-4.08, p = 0.52), RFS (HR = 0.81, 95% CI: 0.42-1.57, p = 0.54), LRFS (HR = 0.57, 95% CI: 0.24-1.36, p = 0.20), and MFS (HR = 1.32, 95% CI: 0.52-3.35, p = 0.56). The median cumulative dose of CDDP was significantly higher in group A (300 mg, interquartile range [IQR]: 240-300) than in group B (240 mg, IQR:160-240) but the frequency of hematological, hepatic, renal, electrolytic, and grade 3-5 any adverse events was not significantly different between two groups. Conclusions: Our study showed no survival difference at 2-year follow-up between 100 mg/m2 and 80 mg/m2 CDDP regimens of definitive CCRT for LAHNC. This result could support the tide of the de-escalation strategy in head and neck cancer treatment. Longer follow-up is necessary and further prospective trials comparing CDDP dosage are warranted.

Purpose Human epidermal growth factor receptor 3 (HER3) has been identified as an important component of many receptor tyrosine kinase-driven cancers. LJM716 is a human IgG monoclonal antibody that binds HER3, trapping it in an inactive conformation. In this study, a phase I dose escalation was performed with a primary objective to establish the maximum tolerated dose and/or the recommended dose of LJM716 in Japanese patients with selected advanced solid tumors. Secondary objectives included the evaluation of the safety and tolerability, preliminary antitumor activity, and pharmacokinetics of LJM716 in Japanese patients. Methods LJM716 was administered intravenously at doses of 10, 20, or 40 mg/kg once weekly, in 28-day cycles, to 12 patients with HER2-amplified breast cancer or gastric cancer, or with esophageal squamous cell carcinoma or squamous cell carcinoma of the head and neck, regardless of HER2 status. Results The maximum tolerated dose was not reached, and the recommended dose was established at 40 mg/kg. No dose-limiting toxicities were observed in the first cycle. The most frequently reported adverse events were diarrhea, fatigue, stomatitis, pyrexia, and paronychia. One unconfirmed partial response was observed in a patient with breast cancer, and 50% of the patients achieved stable disease as the best overall response. Exposure increased with ascending dose, and half-life was estimated to be 11–14 days. No anti-LJM716 antibodies were detected. Conclusions LJM716 was well tolerated in Japanese patients, and a degree of tumor shrinkage was observed. Clinical trial information ClinicalTrials.gov NCT01911936.

Background. Doxorubicin is the key drug for treatment of advanced soft tissue sarcoma (STS). The appropriate dosage of doxorubicin, regarding monotherapy or the role of combination therapy, is unclear. Methods. We retrospectively reviewed patients with advanced or metastatic STS of nonextremities who were treated with doxorubicin-based chemotherapies in our institution. Time to treatment failure (TTF), overall survival (OS), overall response, and prognostic factors for OS were evaluated. Results. Seventy-five patients were enrolled. The median TTF was 4.7 months, and the median OS was 20.1 months. The overall response rate was 20%. Doses of doxorubicin monotherapy did not show significant difference either in TTF or in OS. There were no significant differences in OS between combination therapy and monotherapy, but the TTF with combination therapy was better than monotherapy. The overall response for combination therapy indicated a better response rate. Less number of involved organs, no bulky mass, and a normal CRP level were independent favorable prognostic factors for OS. Conclusions. Combination therapy showed better response and TTF than monotherapy but did not show better OS. Possible prognostic factors for OS were indicated. This retrospective study was approved by the institutional review board. This trial is registered with UMIN000028787.

Objective: In Japan, pazopanib has been made available to soft tissue sarcoma patients, also to patients histologically diagnosed as ineligible for the international Phase 3 study (PALETTE). However, clinical evidence for the use of pazopanib in PALETTE-ineligible patients is currently insufficient. Methods: We retrospectively reviewed medical records of soft tissue sarcoma patients treated with pazopanib at our institute. By pathological review, the patients’ eligibility for the PALETTE was evaluated and the differences in their responses to pazopanib and incidences of adverse events were investigated. Results: From November 2012 to August 2014, a total of 47 patients received pazopanib, 38 (81%) of whom were histologically eligible for the PALETTE, and 9 of whom (19%) were not. The median follow-up time was 7.5 months (range 1.4–20.3 months). An objective response was observed in both groups, but the patients’ survival tended to be longer in the PALETTE-eligible patients; median progression-free survival was 4.5 months vs. 2.9 months (P= 0.15) and overall survival was 10.7 months vs. 7.8 months (P = 0.55), though these differences were not statistically significant. There were no significant differences in the incidence of adverse events by PALETTE eligibility, but dose skipping or dose reduction was more likely to be observed in PALETTE-ineligible patients. Conclusion: Pazopanib is tolerable to soft tissue sarcoma patients ineligible for the PALETTE and some of them respond to pazopanib, but the prognoses of patients ineligible for the PALETTE might be worse than those of PALETTE-eligible patients. The indication of pazopanib for soft tissue sarcoma patients with PALETTE-ineligible histologies should be decided carefully.

Background The effectiveness of the combination chemotherapy of weekly paclitaxel and cetuximab has not yet been compared to that of the current standard regimen, EXTREME (combination of 5-fluorouracil, cisplatin and cetuximab). Methods We retrospectively reviewed the clinical records of R/M SCCHN patients who received cetuximab-containing chemotherapy as a first-line therapy; from these, patients receiving a weekly paclitaxel and cetuximab regimen (cohort A) and the EXTREME regimen (cohort B) were extracted. The responses, prognoses and adverse events of these two cohorts were evaluated. Results A total of 86 patients were included (cohort A, 49; cohort B, 36). Patients with histories of platinum-based chemotherapy were more frequently given the cohort A treatment. Though the response rates were similar in the two cohorts (45% in cohort A and 51% in cohort B; p = 0.83), the progression-free survival (PFS) was significantly more favorable in cohort A by the log-rank test (6.0 months vs 5.0 months; p = 0.027). In the Cox-regression hazard analyses, male gender (hazard ratio [HR] = 2.1, p = 0.010), older age (≥ 70 yo) (HR = 5.0, p = 0.018), PS 0 (HR = 2.2, p = 0.027), no history of platinum chemotherapy (HR = 3.2, p = 0.003) and the presence of a tracheostomy (HR = 2.3, p = 0.039) were favorable factors within cohort A. Conclusion In selected R/M SCCHN patients, the combination of weekly paclitaxel and cetuximab could be the better treatment option than the EXTREME regimen.

Background Precision medicine using next gene sequencing (NGS) of tumor tissues has become mainstream of cancer therapy. Liquid biopsy is minimally invasive Method of sampling to assess tumor genotypes, and would be useful for detecting targetable mutations, follow-up during therapy, and detecting relapse, but more data are needed to clarify its significance. We show some preliminary data for liquid biopsy to detect actionable mutations in various cancer patients. Method We analyzed peripheral blood (14 ml) of patients with various cancers resistant to or without standard therapy and purified circulating cell-free DNA and RNA, then sequenced with customized Oncomine Pan-cancer cell free assay to detect actionable mutations in 95 genes. Data would be confirmed with sequencing of cancer tissues if possible, and be followed during therapy. Results From September 2018 to February 2019, 41 patients were analyzed. Of the 41 patients, primary loci of cancer are breast (n = 12), pancreas (n = 7), soft tissue sarcoma (n = 6), uterine (n = 5), head and neck (n = 3), ovary (n = 3), urothelial (n = 2), others (n = 3). The median age was 57 (25-78) years, performance status was 0-1 in all patients. No actionable mutation was detected in 7 patients. In other 34 patients, some significant mutations could be detected. Of those mutations, TP53 mutations were detected in 20 patients, PIK3CA mutations in 10, KRAS mutations in 7, AKT1 mutation in 1, BRAF mutation in 1, MTOR mutation in 1, FGFR3 amplification in 3. Conclusion The results suggest that actionable or druggable mutation can be detected by liquid biopsy using NGS. Further validation with tumor tissue examination and targeting therapy is needed.

e18067Background: Concurrent chemoradiotherapy (CRT) with single agent cisplatin for patients with head and neck cancers (HNC) have been used as the standard treatment for a long time. Although rec...

Although high-dose cisplatin is the standard regimen of concurrent chemoradiotherapy (CCRT) for locally advanced head and neck squamous cell carcinoma (HNSCC), varying levels of patient tolerance towards cisplatin have been reported, and the predictive factors of cisplatin tolerance remain to be elucidated. The present study retrospectively reviewed newly diagnosed HNSCC patients who received CCRT. Cisplatin (80 mg/m2) was administered every 3 weeks. The proportion of high-dose cisplatin-tolerant patients (cumulative cisplatin dose, ≥200 mg/m2) was determined, and the predictive factors of cisplatin tolerance were analyzed in a logistic regression analysis. Between June 2006 and March 2013, a total of 159 patients were treated with CCRT. The median follow-up time was 36.7 months. A total of 73 patients (46%) tolerated a cumulative cisplatin dose ≥200 mg/m2; male gender [odds ratio (OR), 25.00; P=0.005] and high body surface area (BSA) (>1.80 m2; OR, 2.21; P=0.032) were significantly predictive of high-dose cisplatin tolerance. The high-dose cisplatin-tolerant patients had a significantly higher complete response (CR) rate (82 vs. 67%, P=0.045); however, there were no significant between-group differences in the 3-year OS (79.5 vs. 81.2%, P=0.59) or PFS (70.4 vs. 44.6%, P=0.076) by cisplatin tolerance. In clinical practice, approximately one-half of the patients tolerated high-dose cisplatin in CCRT. Male gender and high BSA could be predictive of cisplatin tolerance.

e22541Background: The correlation between relative dose intensity (RDI) and clinical outcome of pazopanib therapy to STS patients in real-world clinical practice has not been established. Methods: ...

Chronic lymphocytic leukemia (CLL) is relatively rare in Japan. Among 46 cases of mature B-cell leukemia, we identified 28 Japanese patients with CLL, including prolymphocytoid and lymphoplasmacytoid morphological variants. Compared with Western patients with CLL, only 52.0% of cases showed the typical immunophenotypic profile. IgG-bearing (15.4%) and clearly CD20-expressing (71.4%) cases were frequently observed. Most cases harbored a mutated immunoglobulin heavy-chain (VH) gene (88.5%) and commonly used a VH3 family member (61.5%) other than VH3-21. During the median follow-up period of 64 months, 20 cases (71.4%) showed an indolent clinical course without any treatment, and six cases (21.4%) were accompanied by other malignancies. Binet A stage (p = 0.003), low-risk category according to the modified Rai classification (p = 0.016), and ≤ 15 U/mL level of serum thymidine kinase activity (p = 0.016) were associated with prolongation of treatment-free status. Although Japanese cases of CLL showed heterogeneity in morphology and immunophenotype, most cases arose from post-antigen-selected B cells and presented with indolent clinical behavior.

Background: Human epidermal growth factor receptor 3 (HER3) is implicated in tumor growth, proliferation, drug resistance, and metastasis. LJM716 is a fully humanized anti-HER3 IgG1 monoclonal antibody with single-agent and combination anti-tumor activity in HER2-amplified and neuregulin-expressing xenografts. This open-label dose escalation Phase I study evaluated the safety and tolerability of single-agent LJM716 in Japanese patients (pts) with HER2+ advanced/metastatic breast (BC) or gastric cancer (GC), and recurrent/metastatic esophageal squamous cell carcinoma (ESCC) or squamous cell carcinoma of the head and neck (SCCHN) regardless of HER2 status. Methods: Pts (aged ≥18 years, ECOG PS 0‒2) received intravenous (IV) once-weekly (QW) LJM716 in 28 day cycles. The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended dose (RD). Secondary objectives included safety and tolerability, preliminary anti-tumor activity, and pharmacokinetics. Dose escalation decisions were made based on a synthesis of all relevant data, guided by an adaptive Bayesian logistic regression model (BLRM) on dose limiting toxicities (DLTs). Results: At the data cutoff date of Jun 3, 2015, 12 pts (SCCHN [n = 2], ESCC [n = 2], and HER2+ BC [n = 6] or GC [n = 2]) were enrolled (median age 58 years, 50% male, 58% ECOG PS 0). Pts were treated in 3 dose cohorts of 10‒40 mg/kg QW; the median duration of exposure to LJM716 was 14.0 weeks (range 4.0‒48.1). No DLT was reported during Cycle 1; at 40 mg/kg QW 1 pt experienced a DLT of Grade (Gr) 3 pneumonia aspiration during Cycle 2. The BLRM with overdose control supported the tolerability of LJM716 up to 40 mg/kg QW based on DLTs occurring during Cycle 1. However, DLTs occurring after Cycle 1 were also clinically considered, and 40 mg/kg QW was declared as the RD in Japanese pts; the MTD was not reached. One or more adverse event (AE) suspected as drug related were experienced by 10 (83%) pts; most commonly (≥25%) diarrhea (6 pts [50%]), stomatitis, paronychia, fatigue, and pyrexia (3 pts [25%] each). Four pts (33%) experienced ≥1 Gr 3/4 drug-related AEs (all at 40 mg/kg QW): pneumonia aspiration and neutropenia (1 pt [8%] each) and lymphocyte count decreased (2 pts [17%]). Serious AEs were experienced by 2 pts (17%); Gr 2 nausea and Gr 1 vomiting (not suspected as drug related) and Gr 3 pneumonia aspiration (suspected as drug related). One pt died within the follow up period after the last dose of study drug due to disease progression. LJM716 plasma concentration increased with dose, and mean AUClast and Cmax were similar to those found in Western pts. There were no complete or partial responses; stable disease was reported in 6 (50%) pts. Conclusion: LJM716 was well tolerated with a manageable safety profile, and the RD of LJM716 was established at 40 mg/kg QW IV in Japanese pts - the same RD as determined in Western pts in a separate clinical trial. Clinical trials identifier: NCT01911936. Citation Format: TAITO ESAKI, HISANOBU ODA, TATSUHIRO KAJITANI, TAKAYUKI KOBAYASHI, JUNICHI TOMOMATSU, TOMOYUKI KAKIZUME, TAKAHIRO WATANABE, HIROMI TAKEUCHI, KOICHI FUKINO, SHUNJI TAKAHASHI. Phase I study of the safety and tolerability of LJM716 in Japanese patients with advanced solid tumors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C120.

Background: CCRT is a standard treatment for locally advanced head and neck cancer patients, but mucositis and other gastrointestinal adverse events occur frequently, which often make patients unable to take anything by mouth and need to be fed by gastrostoma feeding. Some patients need gastrostoma for long after the end of CCRT. We investigated risk factors for prolonged duration of gastrostomy. Methods: We retrospectively analyzed non-metastatic head and neck cancer patients treated with CCRT from November 2005 to April 2012 in our hospital. Chemotherapy consisted of cisplatin (CDDP) (80 mg/m2 per 3 weeks), but carboplatin (AUC 1.5 weekly) or docetaxel (10 mg/m2 weekly) was administered in case patients were consider to be intolerable to CDDP according to physicians' estimation. Radiation therapy was performed as three-dimensional radiotherapy (3D-RT) or intensity-modified radiotherapy (IMRT), consisting of 66-70 Gy in 33-35 fractions over 7 weeks. Results: A total of 182 patients (155 male, 27 female; median age 58.4 years) received CCRT, of which 145 (80.0%) received percutaneous endoscopic gastrostomy. Median follow-up time was 21.9 months (range 0.99-71.0 months). One hundred fourteen patients could have removed gastrostoma, of which 95 patients (83%) could have removed within 200 days after last radiation day. In logistic regression analysis, regular use of opioids (p = 0.0079) was associated with prolonged duration of gastrostoma placement. Conclusion: Severe mucositis with pain lead regular use of opioids. In CCRT to head and neck cancer patients, control of mucositis could shorten the duration of gastorstoma placement.

Background: Radiation-induced mucositis is considered mild in cetuximab-based bioradiotherapy (BRT) compared to cisplatin-based chemoradiotherapy (CRT) among head and neck cancer patients. We investigated the difference of opioid usage in CRT and BRT for head and neck cancer. Patients and methods: A single-center, retrospective study was conducted on head and neck cancer patients who started to receive either curative-intent CRT or BRT of 66-70Gy between January 2013 and December 2013. Patients were treated with cisplatin 80 mg/m2 every 3 weeks in CRT group, while cetuximab 400 mg/m2 at the first cycle then 250 mg/m2 weekly in BRT group. Treatment was decided through cancer board, in which patients' age, complications and preference were considered. Regular opioid administration dosage during irradiation and 28 days post-irradiation were converted into cumulative dose of fentanyl. Two-sided t-test at alpha = 0.05 was performed to compare the opioid requirements to control mucositis-induced pain between CRT and BRT groups. Results: A total of 50 patients were enrolled in the study; of which 35 were treated with CRT, and 15 were treated with BRT. Distribution of primary sites was naopharynx in 2(4%), oropharynx in 26(52%), hypopharynx in 8(16%) and larynx in 11(22%) patients. 22 (44%) patients was evaluated as at stage IV, and IMRT was administered to 25 (50%) of study population. Opioid requirements in fentanyl dose was significantly lower at average dose of 15.9 mg (SD: 14.8) in CRT group (n = 35), compared to 5.6mg (SD: 9.7) in BRT group (n = 15); t (48) = 2.46, p = 0.02. Conclusion: Opioid requirements to control mucositis-induced pain during radiotherapy for HNSCC were significantly lower in patients who received BRT compared to patients who received CRT. Further multivariate analyses with presumed confounding factors, such as status of hospitalization and physician in charge, are warranted with sufficient sample size that limited multiple regression in the current study.

Background After the approval of pazopanib for the treatment of soft tissue sarcoma (STS), pneumothorax was reported as an unexpected adverse event during pazopanib treatment. The incidence and risk factors of pneumothorax during pazopanib treatment for STSs have not been established yet. Methods We retrospectively reviewed the cases of all of the STS patients treated with pazopanib between November 2012 and December 2014 at our institute and evaluated the prevalence, incidence, treatment details and risk factors for pneumothorax in the STS patients during pazopanib treatment. Results A total of 58 patients were enrolled; 45 of them had lung and/or pleural lesions at the start of pazopanib treatment. During the median follow-up time of 219 days (range 23–659), 13 pneumothorax events occurred in six patients; the prevalence and incidence of pneumothorax were 10.3 % and 0.56 per treatment-year, respectively. The median onset of pneumothorax was day 115 (range 6–311). No patients died of pneumothorax, but pazopanib was interrupted in 10 events and chest drainage was performed in eight events. Pazopanib continuation or restart after the recovery from pneumothorax was conducted after 9 of the 13 events. The median progression-free survival of patients with and without pneumothorax events were 144 and 128 days (p = 0.89) and the median overall survival periods were 293 and 285 days (p = 0.69), respectively. By logistic regression analyses, the maximum diameter of the lung metastases ≥ 30 mm (OR 13.3, 95 % CI 1.1–155.4, p = 0.039) and a history of pneumothorax before the pazopanib induction (OR 16.6, 95 % CI 1.1–256.1, p = 0.045) were significantly predictive of pneumothorax. Conclusions In our retrospective analysis, pneumothorax was observed in 10.3 % of 58 STS patients during pazopanib treatment. The diameter of the lung metastases and a history of pneumothorax could be useful for evaluating the risk of pneumothorax in pazopanib treatment.

e21527 Background: After the approval of pazopanib for the treatment of STS, pneumothorax was reported as an unexpected adverse event during pazopanib treatment. However, the incidence and risk fac...