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Eribulin use in MBC (Metastatic breast cancer) in resource limited setting
abstracts
P3 079
The case of non-small cell lung cancer followed by lip lymphoproliferative disease after immunotherapy
Tomoaki Sonoda1, Yuko Waseda1, Shiro Iino2, Yoshiaki Imamura3, Mai Takeuchi4, Yukihiro Umeda1, Miwa Morikawa1, Masaki Anzai1, Tamotsu Ishizuka1 1 Third Department of Internal Medicine, University of Fukui, 2Dermatology, University of Fukui Hospital, 3Division of Surgical Pathology, University of Fukui Hospital, 4 Department of Pathology, Kurume University Case: 74 y.o. male Chief Complaint: Lower lip nodule Present History: On July in XXXX, left hilar tumor was detected by chest computed tomography, and the patient was admitted to our hospital for scrutiny and treatment. It was diagnosed as stage IVa non-small cell lung cancer with undecidable histopathological subtype.Tumor proportion score of PD-L1 had shown 75%. Since Aug. in XXXX, Pembrolizumab was started. The tumor soon became smaller, so the therapy was thought to be effective. However, after 4 courses of those therapies, lower lip nodules appeared on October. Clinical Course: Lower lip nodule had grown and formed a tumor in 1cm diameter, with scar in the central area and angiogenesis in the peripheral area. Lip tumor biopsy was performed at the end of October. In dermic layer, large cells with strain nucleus had increased. Abnormal cells showing CD3þ, CD4þ, CD8þ, TIA-1þ, CD30þ, EBER(-), ISH(-), have indicated the possibility of T cell lymphoma. Since the association between immunotherapy and the lip nodule could not be denied, immunotherapy was ceased. In order to establish an accurate diagnosis of the lip tumor, resection of the nodule was carried out. At that time, the tumor had shrunk spontaneously, and the large abnormal cells had disappeared, which were detected in incisional biopsy. Considered with pathological findings and clinical course, primary skin lymphoproliferative diseases (LPD) had been diagnosed. As lung lesion was also enlarged simultaneously, Re-bronchoscopic exam revealed not LPDs but progression of cancer in the lung. Discussion: LPD was confined in dermal layer of skin, occurred and disappeared in natural course. As the size of lip tumor decreased after cessation of immunotherapy, it was supposed that immunodeficiency due to the effect of Pembrolizumab might induce LPD.
P3 091
Impact of cytogenetic abnormalities on response to azacitidine in patients with myelodysplastic syndrome
Hiroko Iizuka1, Keiji Sugimoto1, Haruko Takizawa1, Mutsumi Wakabayashi1, Sakura Sakajiri1, Yasunobu Sekiguchi1, Masaaki Noguchi1, Norio Komatsu2 1 Department of Hematology, Juntendo University Urayasu Hospital, 2Department of Hematology, Juntendo University School of Medicine Background: The AZA-001 phase III randomized study showed that azacitidine (AZA) significantly improved overall survival (OS) compared with conventional care in highrisk myelodysplastic syndrome (MDS), but prolonged treatment of 4-6 cycles is required before a failure to achieve response can be declared. Although selection of patients who are unlikely to derive benefit from AZA has become a top clinical priority, prognostic factors for response to and survival with AZA remain unclear. Here we examined prognostic factors for AZA in MDS patients in our hospital. Patients and Methods: We retrospectively analyzed MDS patients treated with AZA between November 2011 and June 2018 in our hospital. Predictors of response were baseline cytogenetic characteristics (including IPSS-R cytogenetic classification) and the number of cytogenetic abnormalities. Univariate analyses were performed with logrank tests and OS was measured from the onset of AZA. Results: The male: female ratio was 4:1. Median age was 72 years, and median number of cycles of AZA was 11. Univariate analysis identified high score for IPSS-R cytogenetic classification and large number of cytogenetic abnormalities as factors associated with
vi142 | Poster Session
poor OS. In particular, patients with 17p abnormalities, possibly related to the presence of TP53 mutation, showed significantly shorter OS. Most rapidly developed leukemia and treatment became difficult to continue (median number of cycles of AZA, 2). Conclusion: In the group with a high score for IPSS-R cytogenetic classification and large number of cytogenetic abnormalities, few patients showed survival advantage or delayed transformation to a leukemic state despite receiving AZA. An alternative to AZA monotherapy is considered necessary for patients expected to show poor response to AZA.
P3 094
Yttrium-90 ibritumomab tiuxetan consolidation versus rituximab maintenance therapy for indolent non-Hodgkin lymphoma
Masaki Iino, Takeo Yamamoto, Tomoya Sato, Yuma Sakamoto Department of Hematology, Yamanashi Prefectural Central Hospital Background: Indolent non-Hodgkin lymphoma is a common B-cell lymphoma that is considered incurable. Post-remission therapies seek to prolong survival. Rituximab (R) maintenance and yttrium-90 ibritumomab tiuxetan (90Y-IT) consolidation are promising post-remission therapies. However, until now, no trials have compared their efficacy and adverse effects. Method: To this effect, we retrospectively examined 75 patients with consecutive indolent lymphoma with complete response or partial response after initial chemotherapy between January 2008 and December 2018. Patients received either 90Y-IT consolidation (27 patients) or R maintenance therapy (2 years, every 2 months, 48 patients). Progression-free survival (PFS), overall survival (OS), and time to next treatment (TTNT) from the start of post-remission therapies were estimated using the KaplanMeier Method, and adverse effects were evaluated. Result: After a median follow-up of 3.6 years (range, 0.5-13.1 years), 5-year PFS of 90YIT consolidation and R maintenance therapy were 75.5% and 82.4%, respectively (logrank test, p ¼ 0.839). OS of 90Y-IT consolidation and R maintenance therapy were 100% and 97.8%, respectively (log-rank test, p ¼ 0.465). Median TTNT of 90Y-IT consolidation and R maintenance therapy were not achieved (log-rank test, p ¼ 0.804). The most common adverse event with 90Y-IT consolidation was hematotoxicity, whereas lower rates and grades of cytopenia were observed in patients who received R maintenance therapy. Secondary malignancies were observed in 1 patient (4%) who received 90Y-IT consolidation and in 2 patients (4.2%) who received R maintenance therapy (Fisher’s exact test, p ¼ 1.00). Conclusion: 90Y-IT consolidation and R maintenance therapy were similar with respect to PFS, OS, and TTNT. However, the features and grades of adverse effects were significantly different. Patient-specific characteristics should be considered while choosing between these post-remission therapies.
P3 104
Eribulin use in MBC (Metastatic breast cancer) in resource limited setting
Rakesh Roy, Abhijit Sarkar Medical Oncology Dept, Saroj Gupta Cancer Centre & Research Institute, India Back ground Eribulin is an anticancer agent derived from halichondrins acts at the level of microtubules but the site is different from that of taxanes. EMBRACE trial showed that even after several lines of chemotherapy in MBC, eribulin offered survival advantage against treatment of physician’s choice with a more better effect in triple negative breast cancers. Cost and neutropenia are the chief limitations of eribulin therapy, thereby restricting usage in resource limited settings. Methods: From a tertiary care charitable cancer institution of Eastern India from Jan 2017 to Feb 2019, 26 patients with MBC received Eribulin. 10 patients were triple negative, 3 were triple positive, rest were hormone receptor positive. ECOG PS ranged from 0-1 and all patients had extensive visceral involvement mandating chemotherapy. 3 patients received concomitant Trastuzumab. Results: The median number of cycles administered were 8 (d1 and d8). 21 patients completed 6 cycles. Interval radiological assessment as per RECIST revealed PR in 4 patients, PD in 5 patients, SD in 17 patients with CR none. Filgrastim was given on day 2,3 and again repeated on day 8,9. None of the patients developed febrile neutropenia. Delay in cycle interval was noted in 3 patients, but none beyond 7 days. There were no incidence of peripheral neuropathy. 5 patients got this drug after anthracycline and taxane progression, while remaining patients got either after capecitabine or navelbine or both. Interestingly, line of therapy did not modify the response, nor did the receptor statu. Quality of life was better during treatment with eribulin compared to the QOL experienced during any of the previous therapy. Conclusion: Considering ease of administration, no hypersensitivity issues, good safety profile, beneficial clinical response and maintenance of good QOL, this drug can be considered as a very suitable third line after taxane and anthracycline failure in MBC, with cost remaining the main challenge.
Volume 30 | Supplement 6 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.115/5582744 by Northwestern University Library, Serials Department user on 02 December 2019
irAEs in nivolumab therapy and 30 patients (55%) developed irAEs in pembrolizumab therapy. In the univariate analysis, male (Odd Ratio: OR 2.38, p ¼ 0.01), smoker (OR 3.29, p ¼ 0.002), squamous cell carcinoma (OR 2.99, p ¼ 0.0001), pembrolizumab therapy (OR 2.15, p ¼ 0.01), 1st line anti-PD-1 treatment (OR 2.07, p ¼ 0.04), EGFR gene mutation negative (OR 8.77, p ¼ 0.03) were significant predictors of irAEs. Multivariate analysis identified younger age (<75) (OR 2.46, p ¼ 0.02), squamous cell carcinoma (OR 2.94, p ¼ 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 ¼ 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 ¼ 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.
Annals of Oncology
P3 079
The case of non-small cell lung cancer followed by lip lymphoproliferative disease after immunotherapy
Tomoaki Sonoda1, Yuko Waseda1, Shiro Iino2, Yoshiaki Imamura3, Mai Takeuchi4, Yukihiro Umeda1, Miwa Morikawa1, Masaki Anzai1, Tamotsu Ishizuka1 1 Third Department of Internal Medicine, University of Fukui, 2Dermatology, University of Fukui Hospital, 3Division of Surgical Pathology, University of Fukui Hospital, 4 Department of Pathology, Kurume University Case: 74 y.o. male Chief Complaint: Lower lip nodule Present History: On July in XXXX, left hilar tumor was detected by chest computed tomography, and the patient was admitted to our hospital for scrutiny and treatment. It was diagnosed as stage IVa non-small cell lung cancer with undecidable histopathological subtype.Tumor proportion score of PD-L1 had shown 75%. Since Aug. in XXXX, Pembrolizumab was started. The tumor soon became smaller, so the therapy was thought to be effective. However, after 4 courses of those therapies, lower lip nodules appeared on October. Clinical Course: Lower lip nodule had grown and formed a tumor in 1cm diameter, with scar in the central area and angiogenesis in the peripheral area. Lip tumor biopsy was performed at the end of October. In dermic layer, large cells with strain nucleus had increased. Abnormal cells showing CD3þ, CD4þ, CD8þ, TIA-1þ, CD30þ, EBER(-), ISH(-), have indicated the possibility of T cell lymphoma. Since the association between immunotherapy and the lip nodule could not be denied, immunotherapy was ceased. In order to establish an accurate diagnosis of the lip tumor, resection of the nodule was carried out. At that time, the tumor had shrunk spontaneously, and the large abnormal cells had disappeared, which were detected in incisional biopsy. Considered with pathological findings and clinical course, primary skin lymphoproliferative diseases (LPD) had been diagnosed. As lung lesion was also enlarged simultaneously, Re-bronchoscopic exam revealed not LPDs but progression of cancer in the lung. Discussion: LPD was confined in dermal layer of skin, occurred and disappeared in natural course. As the size of lip tumor decreased after cessation of immunotherapy, it was supposed that immunodeficiency due to the effect of Pembrolizumab might induce LPD.
P3 091
Impact of cytogenetic abnormalities on response to azacitidine in patients with myelodysplastic syndrome
Hiroko Iizuka1, Keiji Sugimoto1, Haruko Takizawa1, Mutsumi Wakabayashi1, Sakura Sakajiri1, Yasunobu Sekiguchi1, Masaaki Noguchi1, Norio Komatsu2 1 Department of Hematology, Juntendo University Urayasu Hospital, 2Department of Hematology, Juntendo University School of Medicine Background: The AZA-001 phase III randomized study showed that azacitidine (AZA) significantly improved overall survival (OS) compared with conventional care in highrisk myelodysplastic syndrome (MDS), but prolonged treatment of 4-6 cycles is required before a failure to achieve response can be declared. Although selection of patients who are unlikely to derive benefit from AZA has become a top clinical priority, prognostic factors for response to and survival with AZA remain unclear. Here we examined prognostic factors for AZA in MDS patients in our hospital. Patients and Methods: We retrospectively analyzed MDS patients treated with AZA between November 2011 and June 2018 in our hospital. Predictors of response were baseline cytogenetic characteristics (including IPSS-R cytogenetic classification) and the number of cytogenetic abnormalities. Univariate analyses were performed with logrank tests and OS was measured from the onset of AZA. Results: The male: female ratio was 4:1. Median age was 72 years, and median number of cycles of AZA was 11. Univariate analysis identified high score for IPSS-R cytogenetic classification and large number of cytogenetic abnormalities as factors associated with
vi142 | Poster Session
poor OS. In particular, patients with 17p abnormalities, possibly related to the presence of TP53 mutation, showed significantly shorter OS. Most rapidly developed leukemia and treatment became difficult to continue (median number of cycles of AZA, 2). Conclusion: In the group with a high score for IPSS-R cytogenetic classification and large number of cytogenetic abnormalities, few patients showed survival advantage or delayed transformation to a leukemic state despite receiving AZA. An alternative to AZA monotherapy is considered necessary for patients expected to show poor response to AZA.
P3 094
Yttrium-90 ibritumomab tiuxetan consolidation versus rituximab maintenance therapy for indolent non-Hodgkin lymphoma
Masaki Iino, Takeo Yamamoto, Tomoya Sato, Yuma Sakamoto Department of Hematology, Yamanashi Prefectural Central Hospital Background: Indolent non-Hodgkin lymphoma is a common B-cell lymphoma that is considered incurable. Post-remission therapies seek to prolong survival. Rituximab (R) maintenance and yttrium-90 ibritumomab tiuxetan (90Y-IT) consolidation are promising post-remission therapies. However, until now, no trials have compared their efficacy and adverse effects. Method: To this effect, we retrospectively examined 75 patients with consecutive indolent lymphoma with complete response or partial response after initial chemotherapy between January 2008 and December 2018. Patients received either 90Y-IT consolidation (27 patients) or R maintenance therapy (2 years, every 2 months, 48 patients). Progression-free survival (PFS), overall survival (OS), and time to next treatment (TTNT) from the start of post-remission therapies were estimated using the KaplanMeier Method, and adverse effects were evaluated. Result: After a median follow-up of 3.6 years (range, 0.5-13.1 years), 5-year PFS of 90YIT consolidation and R maintenance therapy were 75.5% and 82.4%, respectively (logrank test, p ¼ 0.839). OS of 90Y-IT consolidation and R maintenance therapy were 100% and 97.8%, respectively (log-rank test, p ¼ 0.465). Median TTNT of 90Y-IT consolidation and R maintenance therapy were not achieved (log-rank test, p ¼ 0.804). The most common adverse event with 90Y-IT consolidation was hematotoxicity, whereas lower rates and grades of cytopenia were observed in patients who received R maintenance therapy. Secondary malignancies were observed in 1 patient (4%) who received 90Y-IT consolidation and in 2 patients (4.2%) who received R maintenance therapy (Fisher’s exact test, p ¼ 1.00). Conclusion: 90Y-IT consolidation and R maintenance therapy were similar with respect to PFS, OS, and TTNT. However, the features and grades of adverse effects were significantly different. Patient-specific characteristics should be considered while choosing between these post-remission therapies.
P3 104
Eribulin use in MBC (Metastatic breast cancer) in resource limited setting
Rakesh Roy, Abhijit Sarkar Medical Oncology Dept, Saroj Gupta Cancer Centre & Research Institute, India Back ground Eribulin is an anticancer agent derived from halichondrins acts at the level of microtubules but the site is different from that of taxanes. EMBRACE trial showed that even after several lines of chemotherapy in MBC, eribulin offered survival advantage against treatment of physician’s choice with a more better effect in triple negative breast cancers. Cost and neutropenia are the chief limitations of eribulin therapy, thereby restricting usage in resource limited settings. Methods: From a tertiary care charitable cancer institution of Eastern India from Jan 2017 to Feb 2019, 26 patients with MBC received Eribulin. 10 patients were triple negative, 3 were triple positive, rest were hormone receptor positive. ECOG PS ranged from 0-1 and all patients had extensive visceral involvement mandating chemotherapy. 3 patients received concomitant Trastuzumab. Results: The median number of cycles administered were 8 (d1 and d8). 21 patients completed 6 cycles. Interval radiological assessment as per RECIST revealed PR in 4 patients, PD in 5 patients, SD in 17 patients with CR none. Filgrastim was given on day 2,3 and again repeated on day 8,9. None of the patients developed febrile neutropenia. Delay in cycle interval was noted in 3 patients, but none beyond 7 days. There were no incidence of peripheral neuropathy. 5 patients got this drug after anthracycline and taxane progression, while remaining patients got either after capecitabine or navelbine or both. Interestingly, line of therapy did not modify the response, nor did the receptor statu. Quality of life was better during treatment with eribulin compared to the QOL experienced during any of the previous therapy. Conclusion: Considering ease of administration, no hypersensitivity issues, good safety profile, beneficial clinical response and maintenance of good QOL, this drug can be considered as a very suitable third line after taxane and anthracycline failure in MBC, with cost remaining the main challenge.
Volume 30 | Supplement 6 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.115/5582744 by Northwestern University Library, Serials Department user on 02 December 2019
irAEs in nivolumab therapy and 30 patients (55%) developed irAEs in pembrolizumab therapy. In the univariate analysis, male (Odd Ratio: OR 2.38, p ¼ 0.01), smoker (OR 3.29, p ¼ 0.002), squamous cell carcinoma (OR 2.99, p ¼ 0.0001), pembrolizumab therapy (OR 2.15, p ¼ 0.01), 1st line anti-PD-1 treatment (OR 2.07, p ¼ 0.04), EGFR gene mutation negative (OR 8.77, p ¼ 0.03) were significant predictors of irAEs. Multivariate analysis identified younger age (<75) (OR 2.46, p ¼ 0.02), squamous cell carcinoma (OR 2.94, p ¼ 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 ¼ 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 ¼ 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.
Annals of Oncology