CMET-21. A PHASE IB STUDY OF PROTON CRANIOSPINAL IRRADIATION FOR THE TREATMENT OF SOLID TUMOR LEPTOMENINGEAL METASTASES

Abstract Leptomeningeal metastases (LM) is associated with limited survival and treatment options for patients with solid tumor malignancies. While focal radiotherapy is effective for local palliation, it lacks durability due to cerebrospinal fluid (CSF) tumor cells reseeding. Craniospinal irradiation (CSI) in contrast treats the entire central nervous system (CNS) compartment thus potentially improves disease control. We performed a phase IB study of proton CSI using 30CGE in 10 fractions for treating solid tumor LM (NCT03520504). The primary end point is dose-liming toxicity (DLT) within 1 month of treatment. Clinical outcomes and CSF circulating tumor cells (CTCs) by CellSearch® were evaluated. Overall (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimates. Of the 24 patients enrolled, 4 were excluded from analysis: 3 did not complete treatment due to CNS or systemic disease progression (PD), and 1 completed treatment outside study window. The majority of patients had metastatic lung (55%) and breast (30%) malignancies. At this submission, the median follow-up was 2.8 months (0.5–9.4 months). No DLT was observed. Treatment-related grade 2+ toxicities were: fatigue (G2=43%), anorexia (G2=5%), anemia (G2=10%), thrombocytopenia (G3=5%, G2=10%), and leukopenia (G3=14%, G2=14%). Median survival is not reached with 17 patients (85%) alive with stable/improved LM including 2 with durable CNS control for >9 months, 1 patient alive with CNS and systemic PD at 3.7 months, 2 patients died at 3.6 and 5.1 months with CNS and systemic PD. At 3-month, OS and PFS were 100% and 90% (95% CI 100–72%), respectively. In the 13 patients with CSF CTCs evaluation, decreased quantifiable CTCs at 1-month after proton CSI correlated significantly with improved CNS PFS (log-rank p=0.014). These early findings suggest that proton CSI is a safe and potentially effective treatment for patients with solid tumor LM. CSF biomarkers assessment is needed to better elucidate predictors of response.

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Clinical trial of proton craniospinal irradiation for leptomeningeal metastases

Neuro-Oncology ◽

10.1093/neuonc/noaa152 ◽

2020 ◽

Author(s):

T Jonathan Yang ◽

Neil A Wijetunga ◽

Josh Yamada ◽

Suzanne Wolden ◽

Michelle Mehallow ◽

...

Keyword(s):

Solid Tumors ◽

Treatment Options ◽

Prospective Trial ◽

Progression Free Survival ◽

Medical Intervention ◽

Leptomeningeal Metastases ◽

Craniospinal Irradiation ◽

Hematologic Toxicity ◽

Grade 3 ◽

Entire Central Nervous System

Abstract Background Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. Methods We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). Results We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment–related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention. The median CNS PFS was 7 months (95% CI: 5–13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months. Conclusion Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients.

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Cerebrospinal fluid circulating tumor cells as a predictive biomarker for proton craniospinal irradiation for leptomeningeal metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2011 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2011-2011

Author(s):

N. Ari Wijetunga ◽

Adrienne Ann Boire ◽

Yoshiya Yamada ◽

Rachna Malani ◽

Maria Diaz ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Solid Tumor ◽

Proportional Hazards ◽

Leptomeningeal Metastasis ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Craniospinal Irradiation

2011 Background: Leptomeningeal metastasis (LM) involves seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges. Proton craniospinal irradiation (pCSI) has been shown to be potentially effective for patients with solid tumor LM. We evaluated whether CSF circulating tumor cells (CSF-CTC) and neuroimaging correlate with outcomes in patients with LM treated with pCSI. Methods: We reviewed a single-institution retrospective database of patients treated with pCSI for LM between 2018-2020 who had ≥ 3 months (mos.) follow-up and identified 58 patients. Pre-pCSI CSF-CTC using CellSearch and magnetic resonance imaging (MRI) data, and post-pCSI CSF-CTC nadir before initiation of new cancer-directed therapy were assessed. The optimal cutoff for pre-pCSI CSF-CTC was determined using maximally selected rank statistics. Kaplan Meier analysis was used to identify univariate correlates with CNS progression free survival (CNS PFS) and overall survival (OS), calculated from start of pCSI. Multivariate Cox proportional hazards modeling was used to test independence of univariate associations. Results: The median follow-up for patients who were censored (n = 15, 26%) was 15 mos. (interquartile range (IQR): 9 -21). Most patients were diagnosed with lung (n = 27, 47%) or breast cancer (n = 22, 38%). The median CNS PFS and OS were 6 mos. (IQR: 3 – 9) and 8 mos. (IQR: 5 – 18), respectively. Of the 49 patients with pre-pCSI CSF-CTCs analyzed, CSF-CTCs were identified in 43 (88%). Pre-pCSI CSF-CTC< 53/3mL was associated with improved CNS PFS (11.8 vs 6.0 mos., p = 0.01), and a trend toward improved OS (16.7 vs 7.7 mos., p = 0.08). On pre-pCSI MRI, patients with parenchymal brain metastases (n = 33, 57%) had worse OS (6.7 vs 12.7 mos., p = 0.01) but not CNS PFS. Patients with both brain and spine LM (n = 42, 72%) compared to those only one site or no visible disease (n = 16, 28%) showed worse CNS PFS (5.8 vs 7.5 mos., p = 0.03) and OS (7.7 vs 16.7 mos., p = 0.05). In a multivariate model, pre-pCSI CSF-CTC was significantly associated with CNS PFS (p = 0.03) while brain and spine LM on MRI was not (p = 0.20) No patient had an increase in CSF-CTC immediately post-pCSI, and in those with both detectable pre-pCSI CSF-CTCsand a post-pCSImeasurement(n = 29, 50%), the median decrease at nadir was 37/3mL (range: 0-200) occurring at a median of 1.6 mos. (range: 0.5 -5.2). A decrease in CSF-CTC > 37/3mL was associated with improved CNS PFS (7.1 vs 4.4 mos., p = 0.04) but not OS (12.5 vs.7.7 mos., p = 0.2). Conclusions: Proton CSI is an effective treatment for patients with solid tumor LM and can result in prolonged disease control in some patients. Lower CSF-CTC count prior to pCSI and larger changes after pCSI are predictive of survival outcomes, arguing for early pCSI intervention for solid tumor LMD. Early treatment escalation after pCSI can be considered for patients with high pre-pCSI CSF-CTC and a smaller nadir post-pCSI.

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Weekly docetaxel and cisplatin with capecitabine and bevacizumab (AVDCX) in patients with advanced esophagogastric cancer: Results of a phase Ib/II study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15078 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15078-e15078

Author(s):

Ofer Purim ◽

Yulia Kundel ◽

Udi Sadeh Gonik ◽

Efraim Idelevich ◽

Gal Medalia ◽

...

Keyword(s):

Phase Ii ◽

Response Rate ◽

Performance Status ◽

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Phase Ib ◽

Weekly Docetaxel ◽

Esophagogastric Cancer ◽

Dose Levels

e15078 Background: Many efforts are being made to improve treatment options for advanced esophagogastric cancer (AEGC). The aim of this phase Ib/II study was to evaluate the safety and efficacy of a novel regimen, AVDCX, consisting of weekly docetaxel and cisplatin together with capecitabine and bevacizumab, in AEGC. Methods: Patients with AEGC received treatment with different dose levels of AVDCX (cisplatin and docetaxel 25-35 mg/m2, days 1,8, capecitabine 1,600 mg/m2days 1-14, bevacizumab 7.5 mg/kg, day 1, Q:21 days). To assure regimen's safety a short phase Ib part, with three dose levels, was planned. The study's primary objectives were to establish the recommended phase II doses of docetaxel and cisplatin in AVDCX and to determine the tumor response rate. Results: The study was closed early, after the accrual of 22 patients, due to accumulating toxicity-related deaths. The median age was 59 years and 77% of patients had gastric or gastroesophageal adenocarcinomas. Grade ≥3 adverse events were documented in 18 patients (82%) and these were usually neutropenia (36%), fatigue (54%) or diarrhea (23%). There were three fatal toxicities (14%): mesenteric thromboembolism, gastric perforation and pancytopenic sepsis. Eventually, the recommended phase II doses of cisplatin and docetaxel were determined to be 25 mg/m2 and 30 mg/m2, respectively. Twenty-one patients were evaluable for response: 12 (54%) had partial response (PR), 4 (18%) had stable disease (SD) and none had complete response (CR). The objective response rate (CR+PR) was 54% and the disease control rate (CR+PR+SD) was 72%. Eighteen patients (82%) derived a clinical benefit: improvement of pain, weight or performance status without a deterioration of any of these factors, from treatment. The median overall survival was 11.3 months (range, 1.5-39.2+ months) and median progression-free survival was 8.7 months (range, 1.3–26.6 months). The 2-year OS rate reached 22.7%. Conclusions: AVDCX was associated with bevacizumab-related fatal toxicities. It seems to reproduce the efficacy of bevacizumab regimen AVAGAST trial, without a clue for significant improvement over common docetaxel regimens in AEGC.

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Updated results of single-agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.7515 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 7515-7515 ◽

Cited By ~ 4

Author(s):

Christian Grommes ◽

Igor T. Gavrilovic ◽

Thomas Joseph Kaley ◽

Craig Nolan ◽

Antonio Marcilio Padula Omuro ◽

...

Keyword(s):

Adverse Events ◽

Drug Treatment ◽

Clinical Response ◽

Systemic Disease ◽

Treatment Options ◽

Single Agent ◽

Progression Free Survival ◽

Primary Brain Tumor ◽

Cns Lymphoma ◽

Best Response

7515 Background: PCNSL is an aggressive primary brain tumor with median progression free survival (PFS) after upfront methotrexate-based chemotherapy of 2-3 years. Outcome and treatment options are poor for recurrent/refractory (r/r) disease. Ibrutinib has shown promising clinical response in Mantle cell lymphoma, CLL, Marginal Zone, and Waldenström. This trial investigates Ibrutinib in patients with r/r PCNSL and SCNSL. Methods: Eligible patients had r/r PCNSL or SCNSL, age≥18, ECOG≤2, normal end-organ function, and unrestricted number of CNS directed prior therapies. In patients with SCNSL disease, systemic disease needed to be absent. Results: Twenty-five patients were enrolled (3 at 560 mg; 22 at 840 mg). Median age was 68 (range 21-85); 15 were women. Median ECOG was 1 (0: 2, 1: 15, 2: 8). 64% had PCNSL and 36% SCNSL; 68% had recurrent disease. Seventeen had parenchymal disease, 3 isolated cerebrospinal fluid (CSF) involvement and 5 both. Seven grade 4 adverse events were observed in 7 patients neutropenia (in 3 patients), lymphopenia (2), sepsis (1), and ALT elevation (1). Fourteen patients developed 20 grade 3 toxicities, including lymphopenia in 5 patients, hyperglycemia in 3, ALT elevation in 2, thrombocytopenia in 2, lung infection in 2, AST elevation in 1, neutropenia in 1, urinary tract infection in 1, colitis in 1, febrile neutropenia in 1 and fungal encephalitis in 1. The most common toxicities at any grade were hyperglycemia, thrombocytopenia and anemia of which most were grade 1/2. No grade 5 events have been observed. After a median follow-up of 414 days (range 289-674), 22/25 patients were evaluated for response (3 did not complete at least 15 days of drug treatment). Over all response was 68% (17/22; 77% (17/22) in patient that completed at least 15 days of drug treatment) with 10 CR, 7 PR, 2 SD and 3 PD as best response. The median PFS is 4.6 months (5.4 months in patients that completed at least 15 days of drug treatment; longest: 15.3 months). The median overall survival has not been reached. Conclusions: Patients with CNS lymphoma tolerate Ibrutinib with manageable adverse events. Clinical response was seen in 68% of CNS lymphoma patients. Clinical trial information: NCT02315326.

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RADT-05. CLINICAL OUTCOMES OF PROTON CRANIOSPINAL IRRADIATION FOR PATIENTS WITH LEPTOMENINGEAL CARCINOMATOSIS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.759 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii182-ii182

Author(s):

N Ari Wijetunga ◽

Nader Mohammed ◽

Yoshiya Yamada ◽

Suzanne Wolden ◽

Andrew Seidman ◽

...

Keyword(s):

Breast Cancer ◽

Cox Regression ◽

Progression Free Survival ◽

Leptomeningeal Carcinomatosis ◽

Craniospinal Irradiation ◽

Patient Demographics ◽

Kaplan Meier ◽

Promising Treatment ◽

Entire Central Nervous System

Abstract Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic tumors. Radiotherapy (RT) is integral to LC treatment, and proton craniospinal irradiation (CSI) may make RT more effective by targeting the entire central nervous system (CNS) compartment. We evaluated outcomes in patients treated with proton CSI for LC. We identified 56 patients treated with proton CSI for LC between 2018 and 2020 at our institution. Data on patient demographics, disease and treatment history, cerebrospinal fluid circulating tumor cells (CSF CTCs), and gene alterations were collected. Kaplan Meier analysis and Cox regression models were used to compare correlates with CNS time to progression (TTP), CNS progression-free survival (PFS) and overall survival (OS). Most patients had non-small cell lung cancer (NSCLC, n=27, 48%) or breast cancer (n=21, 38%). The median age was 58 (30-77), and median KPS was 80 (60-90). The median RT dose was 30Gy (25-36). The median follow-up was 12 months (1-22), with 26 (46%) patients alive at the last follow-up. Of 35 (63%) patients who progressed, 6 (11%) progressed in the CNS, 13 (23%) progressed systemically, and 16 (29%) progressed in both. The median TTP, PFS and OS was 8 months (1-21), 6 months (1-21) and 8 months (1-22), respectively. No difference in PFS (7 vs. 6 months, p=0.6) and OS (8 vs. 7 months, p=0.3) was observed between patients with NSCLC and breast cancer. Of patients alive at 3 months, 79% showed stable or improved functional status after CSI. Decreased CSF CTCs immediately post CSI had significantly improved PFS (8 vs. 5 months with no CTC decrease, HR=0.3, p=0.02). Lastly, we identified genetic correlates with survival outcomes. Proton CSI appears to be a promising treatment for LC in select patients, resulting in prolonged CNS disease control and survival. A randomized trial is currently underway to assess its efficacy prospectively.

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A phase II trial of bevacizumab in patients with recurrent solid tumor brain metastases who have failed whole brain radiation therapy (WBRT).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2070 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2070-2070

Author(s):

Priya Kumthekar ◽

Karan Dixit ◽

Sean Aaron Grimm ◽

Rimas Vincas Lukas ◽

Margaret A. Schwartz ◽

...

Keyword(s):

Brain Metastases ◽

Solid Tumor ◽

Stable Disease ◽

Treatment Options ◽

Thrombotic Event ◽

Progression Free Survival ◽

Response Duration ◽

Response Assessment ◽

Open Label

2070 Background: Brain metastases (BM) are the most common intracranial malignancy with overall a poor prognosis estimated at approximately 4 months from time of initial diagnosis for treated patients, and even lower after failing WBRT after which treatment options have been limited and outcomes poor. Methods: This is an open label phase 2 study where patients who have previously failed WBRT received bevacizumab at a dose of 10 mg/kg intravenously every two weeks until CNS disease progression with one cycle being defined as 4 weeks. The primary endpoint was objective radiographic tumor response as defined by modified Response Assessment in Neuro-oncology (RANO) criteria. Secondary endpoints included progression free survival (PFS) at 6 months, time to progression, time to response, duration of response, overall survival (OS), quality of life (QOL) as measured by the FACT-G and FACT-Br and safety. Results: A total of 27 patients were consented and registered to study of which 24 were evaluable for ORR (3 came off study prior to first follow up MRI brain). Medianage was 53 (range 27-73), median number of cycles was 5.5 (range 1-20) with a median follow up of 8.7 months (range 2.4-47.9mo). Of the 24evaluable patients, there were 6 Partial response, 16 stable disease and 2progressive disease. The 6 month PFS: 46% (95% CI: 25% - 67%) and median PFS was 5.3 months. Median OS was 9.5 months (95% confidence interval 6.3m – 15.0m). For the patients who completed sequential QOL assessments, there was no significant decline in QOL but there was a nonsignificant improvement in the FACT-Br scores. Overall, treatment was well tolerated with 3grade 3 adverse events seen: hypertension (n = 3), headache (n = 1) and thrombotic event (n = 1). Conclusions: For this WBRT failure BM population, we were able to show a 25% disease response to bevacizumab therapy along with good drug tolerability and no noted central nervous system bleeding. Improved survival as compared to historical controls was seen 9.5 m. Of the 24 evaluable patients, 81% (22/24) experienced clinical benefit defined as stable disease or better. Bevacizumab therapy could be a viable option for solid tumor BM patients who experience progression following WBRT, however a larger trial is required to confirm this data. Clinical trial information: NCT01898130.

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Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients With Metastatic Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.8923 ◽

2008 ◽

Vol 26 (19) ◽

pp. 3213-3221 ◽

Cited By ~ 1128

Author(s):

Steven J. Cohen ◽

Cornelis J.A. Punt ◽

Nicholas Iannotti ◽

Bruce H. Saidman ◽

Kert D. Sabbath ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Treatment Options ◽

Progression Free Survival ◽

Immunomagnetic Separation ◽

Prognostic Information ◽

Free Survival

PurposeAs treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.Patients and MethodsIn a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.ResultsPatients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.ConclusionThe number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.

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P14.42 Neratinib for treatment of leptomeningeal metastases from HER2-positive breast cancer in extended access program: preliminary results

Neuro-Oncology ◽

10.1093/neuonc/noab180.159 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii46-ii46

Author(s):

A Pellerino ◽

R Palmiero ◽

F Bruno ◽

F Mo ◽

E Muscolino ◽

...

Keyword(s):

Breast Cancer ◽

Median Time ◽

Systemic Disease ◽

Progression Free Survival ◽

Leptomeningeal Metastases ◽

Her2 Positive ◽

Poor Overall Survival ◽

Adjuvant Trastuzumab ◽

Her2 Breast Cancer ◽

Radiological Response

Abstract BACKGROUND Leptomeningeal metastases (LM) occur in 5% of human epidermal growth factor receptor 2 (HER2) breast cancer (BC) with a poor overall survival (OS) of 3 months. Neratinib is an oral, irreversible tyrosine kinase pan-inhibitor that was approved by FDA for the treatment of HER2-enriched BC, who completed a prior adjuvant trastuzumab-based therapy. The aim of the study was to evaluate the activity of neratinib in LM from HER2-positive BC after the failure of multiple lines of treatment, including trastuzumab. PATIENTS AND METHODS Inclusion criteria were as follows: age ≥ 18 years; histological diagnosis of primary HER2-positive BC; newly-diagnosed LM according to LANO criteria; KPS ≥60 at the time of diagnosis of LM; coexistence of BM that have or not received WBRT or radiosurgery; systemic disease with a life expectancy of at least 3 months; concomitant drugs, including capecitabine, trastuzumab, TDM-1, pertuzumab, and hormone therapy were allowed, with the exclusion of lapatinib or other investigational agents. Neratinib was administered 240 mg daily continuously. The primary endpoint was the OS after the diagnosis of LM. Secondary endpoints were progression-free survival (PFS) following the diagnosis of LM, neurological benefit, radiological response rate, and tolerability. RESULTS From January 2018 to April 2021, 9 patients with LM have been enrolled. Median age at the time of diagnosis of LM was 44 years (95%CI 36–59) with a median KPS of 80 (95%CI 60–90). Median time since LM onset from the diagnosis of primary BC was 42 months (95%CI 11–166), and patients underwent a median number of adjuvant treatments before LM of 3 (95%CI 2–5). Three patients developed LM alone, and other 6 had LM associated with multiple brain metastases. Six-months and 1-year OS were 66.7% and 22.3%, respectively, with a median OS of 8 months (95%CI 3–13*). Median PFS was 3.5 months (95%CI 2–6) after the start of treatment. A neurological improvement was reported in 2/9 patients (22.2%), while in other 4/9 patients (44.5%) was achieved a neurological stabilization lasting for a median time of 5 months (95%CI 2–19). The best radiological response was a stable disease in 5/9 patients (55.6%), while no complete or partial response were achieved according to LANO and RANO criteria, respectively. A CSF clearance was observed in 1 patient only (11.1%) following two months of neratinib. Grade III-IV adverse events were not reported, and 2 patients only (22.2%) had mild diarrhea correlated with neratinib. CONCLUSION This is the first study that shows that neratinib might be a safe and effective treatment in LM from heavily pretreated HER2-positive BC.

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CMET-16. A PHASE II TRIAL OF BEVACIZUMAB IN PATIENTS WITH RECURRENT SOLID TUMOR BRAIN METASTASES WHO HAVE PROGRESSED FOLLOWING WHOLE BRAIN RADIATION THERAPY (WBRT): FINAL RESULTS

Neuro-Oncology ◽

10.1093/neuonc/noz175.217 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi54-vi54

Author(s):

Priya Kumthekar ◽

Karan Dixit ◽

Sean Grimm ◽

Rimas Lukas ◽

Margaret Schwartz ◽

...

Keyword(s):

Brain Metastases ◽

Solid Tumor ◽

Treatment Options ◽

Thrombotic Event ◽

Progression Free Survival ◽

Response Duration ◽

Response Assessment ◽

Median Number ◽

Open Label

Abstract BACKGROUND Brain metastases (BM) are the most common intracranial tumor with limited treatment options following the progression after WBRT. METHODS This open label phase 2 study for patients have progressed following WBRT enrolled participants who received bevacizumab 10 mg/kg intravenously every two weeks until CNS disease progression (one cycle=4 weeks). The primary endpoint was objective radiographic tumor response as defined by modified Response Assessment in Neuro-oncology (RANO) criteria. Secondary endpoints included safety, progression free survival (PFS), time to response, duration of response, overall survival (OS), and quality of life (QOL) as measured by FACT-G and FACT-Br. RESULTS A total of 27 patients were registered of which 24 were evaluable for ORR (3 came off study prior to first follow up MRI brain). Median age was 53 (range 27–73), median number of cycles was 5.5 (range 1–20) with a median follow up of 8.7 months (range 2.4–47.9mo). Of the 24 evaluable patients, 6 showed radiographic response (Partial response=6, stable disease=16, progressive disease=2, 81% (22/24) experienced clinical benefit). The 6 month PFS: 46% (95% CI: 25% - 67%) and median PFS was 5.3 months. Median OS was 9.5 months (95% confidence interval 6.3m – 15.0m). For the patients who completed sequential QOL assessments, there no decline in QOL seen secondary to treatment and there was a non statistically significant improvement seen in the FACT-Br questionnaire. Overall, treatment was well tolerated with 3 grade 3 adverse events seen: hypertension (n=3), headache (n=1) and thrombotic event (n=1). CONCLUSION For this pretreated BM population with historically poor clinical outcome and survival, we showed disease response with bevacizumab therapy, drug tolerability and improved survival as compared to historical controls. While larger studies are needed to confirm, bevacizumab therapy could be a viable option for solid tumor BM patients who experience progression following WBRT.

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PD-L1 and survival in oral cavity squamous cell carcinoma

Periodontology ◽

10.33925/1683-3759-2020-25-4-287-294 ◽

2020 ◽

Vol 25 (4) ◽

pp. 287-294

Author(s):

S. I. Kutukova ◽

N. P. Beliak ◽

G. A. Raskin ◽

M. S. Mukhina ◽

Yu. V. Ivaskova ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Tumor Cells ◽

Squamous Cell ◽

Immune Cells ◽

Negative Impact ◽

Progression Free Survival ◽

Negative Effect ◽

Effect Of Pd

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.

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