- Email: [email protected]
Palbociclib in clinical use for metastatic breast cancer at a single institution
abstracts
Annals of Oncology P2 062
Selection of chemotherapy based on geriatric assessment for elderly patients with pancreatic cancer
Osamu Maeda1, Ayumu Matsuoka1, Madoka Yanagawa2, Yukie Muroyama3, Masafumi Kuzuya2, Yuichi Ando1 1 Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, 2 Department of Community Healthcare and Geriatrics, Nagoya University Graduate School of Medicine, 3Center for Advanced Medicine and Clinical Research, Department of Advanced Medicine, Nagoya University Hospital
P2 076
Elevated expression of lumican in lung cancer cells promotes bone metastasis through an autocrine regulatory mechanism
Ko-Jiunn Liu1, Kuan-Chung Hsiao1, Pei-Yi Chu2, Gee-Cheng Chang3 National Institute of Cancer Research, National Health Research Institutes, Taiwan, 2 Department of Pathology, Show Chwan Memorial Hospital, Changhua City, Taiwan, 3 Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
1
Background: The median survival time of lung cancer patients with bone metastasis is less than 6 months. Therefore, reducing the incidence of bone metastasis may provide significant clinical benefits for lung cancer patients. Whole genome expression microarray analysis indicated that the gene encoding for lumican, a protein associated with extracellular matrix interaction, was highly expressed in osteotropic lung cancer cell lines with an enhanced capacity of bone metastasis. Further experiments were conducted to reveal the role of lumican in bone metastasis of lung cancer. Methods: The expression of lumican was suppressed in the osteotropic lung cancer cells and the binding capacity to extracellular matrix components, the in vitro migration and invasion ability, and the in vivo bone metastasis capacity of these cells were examined. Exogenous lumican was provided to investigate the autocrine-regulation mechanism of lumican in the bone metastasis of lung cancer cells. Results: Transfection with lumican specific shRNA in the osteotropic lung cancer cells reduced the establishment of in vivo bone metastasis, but not lung metastasis. Reduction of lumican expression also decreased the attachment of lung osteotropic cancer cells to several extracellular matrix components and suppressed cell migration and invasion in vitro. Exogenous lumican restored these reduced capacities of lumicanknockdown cells and promoted the seeding of lung cancer cells in the bone microenvironment. Conclusion: These results suggest that lumican promotes bone metastasis of lung cancer cells through an autocrine regulatory mechanism and blocking this interaction may provide a new therapeutic approach to reduce bone metastasis in lung cancer.
P2 096
Thymoma Associated with Neuromyelitis Optica Spectrum Disorder: A Case Report
Piyakarn Watcharenwong1, Touch Ativitavas1, Thanate Dajsakdipon1, Charungthai Dejthevaporn2 1 Division of Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 2Division of Neurology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Thymoma is one of the most common anterior mediastinal tumors in adults. The wide range of paraneoplastic syndromes associated with thymoma has been reported. There
Volume 30 | Supplement 6 | October 2019
P2 125
Palbociclib in clinical use for metastatic breast cancer at a single institution
Mitsuo Terada, Sawaki Masataka, Hattori Masaya, Yoshimura Akiyo, Gondo Naomi, Kotani Haruru, Adachi Yayoi, Kataoka Ayumi, Sugino Kayoko, Horisawa Nanae, Mori Makiko, Ozaki Yuri, Iwata Hiroji Breast Oncology Department, Aichi Cancer Center Background: The PALOMA2/3 trials demonstrated prominent efficacy of combination therapy of palbociclib (PAL) and endocrine therapy (ET) compared with monotherapy. PAL was approved for metastatic breast cancer in Japan in 2017. We evaluated the efficacy and safety in practice after approval of PAL in Japan. Methods: We retrospectively reviewed patients who newly received PAL at Aichi Cancer Center after Dec 2017. The patients were classified by treatment-line and assessed as follows; clinical benefit rate (CBR) defined as the rate of clinical PR, CR and long SD (more than 6 months) based on physician’s judgment, time to failure (TTF) defined as the duration time of PAL, prior ET response, and adverse events (AEs). TTFs were figured with swimmer’s plot by treatment-line, PAL doses (125, 100, 75mg/day). Results: Between Dec 2017 and Oct 2018, 64 patients were eligible. Median age was 62.5 (37-82). Forty-one patients (64%) had visceral metastasis. PAL was administered for 1st to 3rd line (early-line group) in 52% (n ¼ 33), and for more than 4th line (lateline group) in 48% (n ¼ 31). Combination ETs were aromatase inhibitors (n ¼ 27, 42%), fulvestrant (n ¼ 35, 55%), and tamoxifen (n ¼ 2, 3%). Prior ET was sensitive in 59% (n ¼ 33). The dose reduction was needed in 62% (100mg; n ¼ 19, 75mg; n ¼ 21). Twenty-eight patients (43.8%) were continuing PAL. Overall CBR was 38%. By treatment line, CBR was 51.6% in the early-line group, and 22.6% in the late-line group. Median TTF was 4.6 months (0.2-10.2). There were no significant differences of TTF by treatment-line, prior ET response, and PAL doses. The grade 3-4 hematological toxicity, such as neutropenia and anemia, were observed in 83% (n ¼ 53). Stomatitis, nausea, and fatigue were common, but most of them were grade 1-2. No patients discontinued PAL due to AEs. Conclusions: In the clinical setting, PAL was given in many late line-patients who were not eligible for the PALOMA2/3 trials. Its efficacy was not sufficient, although it was feasible.
P2 126
Study of parvociclib administration patients at our hospital
Mahito Funakoshi1, Srlouichi Kitaguchi2, Naoki Hirabayashi3, Morihito Okada4 Hiroshima City Asa Citizens Hospital, 2Hiroshima City Asa Citizens Hospital, 3Hiroshima City Asa Citizens Hospital, 4Department of Surgical Oncology, Hiroshima University
1
Purpose: Palbociclib (PAL) is an oral molecular targeted drug that specifically inhibits CDK4 / 6. As a result of PALOMA-2 and 3 studies, PFS is extended in combination with primary and secondary hormone therapy in patients with HR-positive HER2-negative advanced recurrent breast cancer. This time, we examined the case of PAL administration in our hospital. Patients and Method: Subjects were 16 patients who received PAL. PAL started with 125 mg. Allowed dose loss (100 mg, 75 mg) up to 2 levels. We examined the clinical findings, side effects, dose loss, and continuation of the treated cases. Result: The 16 cases treated were 43-81 years old and 60.3 years old on average. The metastatic site was bone only 7 cases, pulmonary and lymph node 7 cases, lung 2 cases. The administration line was 2 cases for primary and 14 cases for secondary. At diagnosis, Stage I 2 cases, II 5 cases, III 4 cases, and IV 5 cases. The average postoperative age of 11 cases excluding 5 Stage IV patients is 11.3 years. Adjuvant chemotherapy was
doi:10.1093/annonc/mdz343 | vi131
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.063/5583134 by guest on 25 October 2019
Background: There is no established Method to select chemotherapy regimens for elderly patients with unresectable or recurrent pancreatic cancer. Geriatric assessment (GA) potentially enables the optimization of treatment choice for this group of elderly patients. To validate treatment allocation based on GA, we performed a prospective interventional study of elderly patients with pancreatic cancer. Methods: Eligibility criteria included age 75, potential indication for chemotherapy, history of no prior chemotherapy except for postoperative adjuvant chemotherapy, and the ability to answer a questionnaire. Based on GA, patients were classified into fit, vulnerable or frail groups. Combination with gemcitabine and nanoparticle albumin-bound paclitaxel (GnP), which is the standard treatment for nonelderly patients, was administered to fit patients, gemcitabine alone (Gem) to vulnerable patients, and best supportive care to frail patients. GA was performed before treatment group allocation and at three and six months later. The primary endpoint was the time to treatment failure (TTF). Results: Out of eight patients, five were classified as fit, and three were classified as vulnerable. Three out of the five fit patients received GnP, the other two received Gem, and the three vulnerable patients also received Gem. The median TTF was 20.0 weeks (95% confidence interval; 0-55.7), and the median overall survival was not reached at this time. Three patients who received GnP discontinued the treatment due to adverse events: interstitial lung disease in one patient and drug eruption in two patients. One fit patient who ceased GnP treatment due to drug eruption received FOLFIRINOX and achieved stable disease for over ten months. A vulnerable patient who received Gem was alive for over nine months. Conclusion: GA is a promising procedure for optimizing treatment selection for elderly patients with pancreatic cancer.
are few reported cases of thymoma associated with neuromyelitis optica spectrum disorder (NMOSD). We reported a 52-year-old man who was diagnosed with thymoma type B2 but loss follow-up. After 1 year, he developed subacute ascending paraparesis, bowel-bladder involvement without chest symptoms. The spinal cord syndrome was suspected from physical examination. The whole spine MRI showed multifocal short and long segments of hyperintense T2 lesion in C3/4, C5-1, T6-8, T10 levels. The cerebrospinal fluid revealed aseptic meningitis (WBC 100, lymphocyte 99%, neutrophil 1%, protein 60.8 mg/dL, normal glucose level) and negative for culture or PCR for viruses. The CSF aquaporin-4 were negative. However, the CSF paraneoplastic panel showed a positive for anti-titin. The brain MRI revealed an inhomogeneous isointense T2/FLAIR 1.7 x 2.2 cm at the left temporal lobe. The biopsy of temporal lesion reported as demyelinating disease. The NMOSD with the serology negative was diagnosed. He was treated with 5 days of intravenous methylprednisolone (1 gm/day) but his motor power was not improved. The plasmapheresis was initiated for 5 days. There was minimal improvement but his motor weakness worsened again. The multi-disciplinary team decided to treat underlying thymoma with chemotherapy. CAP regimen (cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and paclitaxel 50 mg/m2) was administrated every 3 week for 4 cycles. His motor power and bowel-bladder function were gradually improved to full recovery. His chest CT showed decrease size of the thymoma. Thymoma could be associated with NMOSD. The treatment of thymoma should be considered to improve the neurological symptoms.
Annals of Oncology P2 062
Selection of chemotherapy based on geriatric assessment for elderly patients with pancreatic cancer
Osamu Maeda1, Ayumu Matsuoka1, Madoka Yanagawa2, Yukie Muroyama3, Masafumi Kuzuya2, Yuichi Ando1 1 Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, 2 Department of Community Healthcare and Geriatrics, Nagoya University Graduate School of Medicine, 3Center for Advanced Medicine and Clinical Research, Department of Advanced Medicine, Nagoya University Hospital
P2 076
Elevated expression of lumican in lung cancer cells promotes bone metastasis through an autocrine regulatory mechanism
Ko-Jiunn Liu1, Kuan-Chung Hsiao1, Pei-Yi Chu2, Gee-Cheng Chang3 National Institute of Cancer Research, National Health Research Institutes, Taiwan, 2 Department of Pathology, Show Chwan Memorial Hospital, Changhua City, Taiwan, 3 Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
1
Background: The median survival time of lung cancer patients with bone metastasis is less than 6 months. Therefore, reducing the incidence of bone metastasis may provide significant clinical benefits for lung cancer patients. Whole genome expression microarray analysis indicated that the gene encoding for lumican, a protein associated with extracellular matrix interaction, was highly expressed in osteotropic lung cancer cell lines with an enhanced capacity of bone metastasis. Further experiments were conducted to reveal the role of lumican in bone metastasis of lung cancer. Methods: The expression of lumican was suppressed in the osteotropic lung cancer cells and the binding capacity to extracellular matrix components, the in vitro migration and invasion ability, and the in vivo bone metastasis capacity of these cells were examined. Exogenous lumican was provided to investigate the autocrine-regulation mechanism of lumican in the bone metastasis of lung cancer cells. Results: Transfection with lumican specific shRNA in the osteotropic lung cancer cells reduced the establishment of in vivo bone metastasis, but not lung metastasis. Reduction of lumican expression also decreased the attachment of lung osteotropic cancer cells to several extracellular matrix components and suppressed cell migration and invasion in vitro. Exogenous lumican restored these reduced capacities of lumicanknockdown cells and promoted the seeding of lung cancer cells in the bone microenvironment. Conclusion: These results suggest that lumican promotes bone metastasis of lung cancer cells through an autocrine regulatory mechanism and blocking this interaction may provide a new therapeutic approach to reduce bone metastasis in lung cancer.
P2 096
Thymoma Associated with Neuromyelitis Optica Spectrum Disorder: A Case Report
Piyakarn Watcharenwong1, Touch Ativitavas1, Thanate Dajsakdipon1, Charungthai Dejthevaporn2 1 Division of Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 2Division of Neurology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Thymoma is one of the most common anterior mediastinal tumors in adults. The wide range of paraneoplastic syndromes associated with thymoma has been reported. There
Volume 30 | Supplement 6 | October 2019
P2 125
Palbociclib in clinical use for metastatic breast cancer at a single institution
Mitsuo Terada, Sawaki Masataka, Hattori Masaya, Yoshimura Akiyo, Gondo Naomi, Kotani Haruru, Adachi Yayoi, Kataoka Ayumi, Sugino Kayoko, Horisawa Nanae, Mori Makiko, Ozaki Yuri, Iwata Hiroji Breast Oncology Department, Aichi Cancer Center Background: The PALOMA2/3 trials demonstrated prominent efficacy of combination therapy of palbociclib (PAL) and endocrine therapy (ET) compared with monotherapy. PAL was approved for metastatic breast cancer in Japan in 2017. We evaluated the efficacy and safety in practice after approval of PAL in Japan. Methods: We retrospectively reviewed patients who newly received PAL at Aichi Cancer Center after Dec 2017. The patients were classified by treatment-line and assessed as follows; clinical benefit rate (CBR) defined as the rate of clinical PR, CR and long SD (more than 6 months) based on physician’s judgment, time to failure (TTF) defined as the duration time of PAL, prior ET response, and adverse events (AEs). TTFs were figured with swimmer’s plot by treatment-line, PAL doses (125, 100, 75mg/day). Results: Between Dec 2017 and Oct 2018, 64 patients were eligible. Median age was 62.5 (37-82). Forty-one patients (64%) had visceral metastasis. PAL was administered for 1st to 3rd line (early-line group) in 52% (n ¼ 33), and for more than 4th line (lateline group) in 48% (n ¼ 31). Combination ETs were aromatase inhibitors (n ¼ 27, 42%), fulvestrant (n ¼ 35, 55%), and tamoxifen (n ¼ 2, 3%). Prior ET was sensitive in 59% (n ¼ 33). The dose reduction was needed in 62% (100mg; n ¼ 19, 75mg; n ¼ 21). Twenty-eight patients (43.8%) were continuing PAL. Overall CBR was 38%. By treatment line, CBR was 51.6% in the early-line group, and 22.6% in the late-line group. Median TTF was 4.6 months (0.2-10.2). There were no significant differences of TTF by treatment-line, prior ET response, and PAL doses. The grade 3-4 hematological toxicity, such as neutropenia and anemia, were observed in 83% (n ¼ 53). Stomatitis, nausea, and fatigue were common, but most of them were grade 1-2. No patients discontinued PAL due to AEs. Conclusions: In the clinical setting, PAL was given in many late line-patients who were not eligible for the PALOMA2/3 trials. Its efficacy was not sufficient, although it was feasible.
P2 126
Study of parvociclib administration patients at our hospital
Mahito Funakoshi1, Srlouichi Kitaguchi2, Naoki Hirabayashi3, Morihito Okada4 Hiroshima City Asa Citizens Hospital, 2Hiroshima City Asa Citizens Hospital, 3Hiroshima City Asa Citizens Hospital, 4Department of Surgical Oncology, Hiroshima University
1
Purpose: Palbociclib (PAL) is an oral molecular targeted drug that specifically inhibits CDK4 / 6. As a result of PALOMA-2 and 3 studies, PFS is extended in combination with primary and secondary hormone therapy in patients with HR-positive HER2-negative advanced recurrent breast cancer. This time, we examined the case of PAL administration in our hospital. Patients and Method: Subjects were 16 patients who received PAL. PAL started with 125 mg. Allowed dose loss (100 mg, 75 mg) up to 2 levels. We examined the clinical findings, side effects, dose loss, and continuation of the treated cases. Result: The 16 cases treated were 43-81 years old and 60.3 years old on average. The metastatic site was bone only 7 cases, pulmonary and lymph node 7 cases, lung 2 cases. The administration line was 2 cases for primary and 14 cases for secondary. At diagnosis, Stage I 2 cases, II 5 cases, III 4 cases, and IV 5 cases. The average postoperative age of 11 cases excluding 5 Stage IV patients is 11.3 years. Adjuvant chemotherapy was
doi:10.1093/annonc/mdz343 | vi131
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.063/5583134 by guest on 25 October 2019
Background: There is no established Method to select chemotherapy regimens for elderly patients with unresectable or recurrent pancreatic cancer. Geriatric assessment (GA) potentially enables the optimization of treatment choice for this group of elderly patients. To validate treatment allocation based on GA, we performed a prospective interventional study of elderly patients with pancreatic cancer. Methods: Eligibility criteria included age 75, potential indication for chemotherapy, history of no prior chemotherapy except for postoperative adjuvant chemotherapy, and the ability to answer a questionnaire. Based on GA, patients were classified into fit, vulnerable or frail groups. Combination with gemcitabine and nanoparticle albumin-bound paclitaxel (GnP), which is the standard treatment for nonelderly patients, was administered to fit patients, gemcitabine alone (Gem) to vulnerable patients, and best supportive care to frail patients. GA was performed before treatment group allocation and at three and six months later. The primary endpoint was the time to treatment failure (TTF). Results: Out of eight patients, five were classified as fit, and three were classified as vulnerable. Three out of the five fit patients received GnP, the other two received Gem, and the three vulnerable patients also received Gem. The median TTF was 20.0 weeks (95% confidence interval; 0-55.7), and the median overall survival was not reached at this time. Three patients who received GnP discontinued the treatment due to adverse events: interstitial lung disease in one patient and drug eruption in two patients. One fit patient who ceased GnP treatment due to drug eruption received FOLFIRINOX and achieved stable disease for over ten months. A vulnerable patient who received Gem was alive for over nine months. Conclusion: GA is a promising procedure for optimizing treatment selection for elderly patients with pancreatic cancer.
are few reported cases of thymoma associated with neuromyelitis optica spectrum disorder (NMOSD). We reported a 52-year-old man who was diagnosed with thymoma type B2 but loss follow-up. After 1 year, he developed subacute ascending paraparesis, bowel-bladder involvement without chest symptoms. The spinal cord syndrome was suspected from physical examination. The whole spine MRI showed multifocal short and long segments of hyperintense T2 lesion in C3/4, C5-1, T6-8, T10 levels. The cerebrospinal fluid revealed aseptic meningitis (WBC 100, lymphocyte 99%, neutrophil 1%, protein 60.8 mg/dL, normal glucose level) and negative for culture or PCR for viruses. The CSF aquaporin-4 were negative. However, the CSF paraneoplastic panel showed a positive for anti-titin. The brain MRI revealed an inhomogeneous isointense T2/FLAIR 1.7 x 2.2 cm at the left temporal lobe. The biopsy of temporal lesion reported as demyelinating disease. The NMOSD with the serology negative was diagnosed. He was treated with 5 days of intravenous methylprednisolone (1 gm/day) but his motor power was not improved. The plasmapheresis was initiated for 5 days. There was minimal improvement but his motor weakness worsened again. The multi-disciplinary team decided to treat underlying thymoma with chemotherapy. CAP regimen (cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and paclitaxel 50 mg/m2) was administrated every 3 week for 4 cycles. His motor power and bowel-bladder function were gradually improved to full recovery. His chest CT showed decrease size of the thymoma. Thymoma could be associated with NMOSD. The treatment of thymoma should be considered to improve the neurological symptoms.