Response-Adapted Treatment with Rituximab/Bendamustine/Mitoxantrone/Dexamethasone and Maintenance Therapy with Rituximab in Patients with Follicular Lymphoma in Relapse or Refractory to First-Line Treatment with Immunochemotherapy. RBMDGELTAMO08 Trial

Abstract Objectives: To evaluate the efficacy and toxicity of a response-adapted therapy with rituximab/bendamustine/mitoxantrone/dexamethasone (RBMD), followed by rituximab (R) maintenance therapy in patients with relapsed or refractory follicular lymphoma (R/R FL) to first-line treatment with R-chemotherapy (R-ChemoT). Material and methods: Multicenter phase II trial including 60 patients with R/R FL, after a first R-ChemoT line. Induction therapy: R 375 mg/m2 IV, day 1; bendamustine 90 mg/m2 IV, days 1 and 2; mitoxantrone 6 mg/m2 IV, day 1; dexamethasone 20 mg/day, PO, days 1 to 5. Cycles of 28 days. Evaluation of response after third cycle. If stable (SD) or progression disease (PD): patient withdrawn from the study. If complete response (CR) or unconfirmed complete response (CRu): administration of fourth cycle. If partial response (PR): administration up to 6 cycles. If CR, CRu, or PR after induction: patient received maintenance therapy with R (375 mg/m2/day every 12 weeks for 2 years). Results: N=60 patients: 50% female, age 63 (32-76) years. Ann Arbor stage III-IV 70% (42/60). FLIPI intermediate-high risk: 50% (30/60). Refractory to R-ChemoT: 18% (11/60). Received RCHOP as first line therapy: 77% (43/60). R maintenance after first line therapy: 43% (26/60). Number of administered RBMD cycles: 4 (1-6). Efectiveness: CR/CRu after 3 cycles (CR-3), 27 patients. Response after induction therapy (4-6 cycles): Overall response (OR), 88.5% (53/60); CR, 58.5% (35/60); CRu, 12% (7/60); PR, 18% (11/60); SD, 1.5% (1/60); PD, 10% (6/60). Median follow-up: 24.41 mo. (15.58-30.15). Progression free survival, median not reached (NR) (28.28-NR). Overall survival, median NR (NR-NR). OR after RBMD in patients who received R maintenance after first line therapy, 96% (25/26; CR + CRu, 65%). OR in patients who did not receive R maintenance after first line therapy, 94% (32/34; CR + CRu, 82%). Safety: Grade 3/4 hematologic toxicity: neutropenia, 60% (n=36; 34 patients received G-CSF); anemia, 2% (n=1); thrombopenia, 4% (n=2). Grade 3/4 infections: 8% (n=4); febrile neutropenia 8%, (n=4). Exitus, 2/60 (PD, cycle 1; influenza A, cycle 5). Grade 3/4 non-hematologic toxicity: infusion reaction, 4% (n=2). No skin reactions. Patient withdrawals before R maintenance therapy: no inclusion criteria (NIC), 2/60; protocol delay of over 4 weeks, 7/60. Forty-four patients began R maintenance therapy (CR-3, 24/44). During R maintenance therapy: PD, 8/44 (18%; 5/8 in CR-3 patients); SD, 1/44 (2.5%); NIC, 3/44 (7%, all CR); protocol delay, 1/44 (2.5%); toxicity, 1/44 (2.5%, myelodysplastic syndrome). Response to R maintenance therapy: OR, 68% (30/44); CR, 61% (27/44; in CR-3 patients, 65%, 17/26); CRu, 4.5% (2/44); PR, 2.5% (1/44). Conclusions: RBMD is an effective and safe alternative for patients with R/R FL who have received first line treatment with R-ChemoT and R maintenance therapy. This response-adapted treatment strategy achieved results similar to the scheme with 6 cycles and may allow reduction of the intensity and duration of induction therapy and minimize toxicity. No skin reactions were reported, possibly due to the inclusion of dexamethasone in the treatment scheme. Disclosures No relevant conflicts of interest to declare.

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Efficacy of platinum-based regimens as the first-line therapy in Chinese patients with advanced TNBC and deleterious BRCA1/2 mutations.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e12565 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e12565-e12565

Author(s):

Nan Wang ◽

Kun Li ◽

Wei-Yao Kong ◽

Xiao-Ran Liu ◽

Meng-Yao Tan ◽

...

Keyword(s):

Chinese Patients ◽

Line Treatment ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Platinum Based Chemotherapy ◽

Significant Difference ◽

Peking University ◽

Grade 3 ◽

First Line Treatment

e12565 Background: Platinum-based therapy remains an effective treatment for triple-negative breast cancer (TNBC), however, the usage is largely limited due to its side effect and rapidly developed drug resistance. High prevalence of BRCA1/2 mutations are reported in TNBC. Here we explored efficacy of platinum-based regimens as the first-line treatment for Chinese patients (pts) with advanced TNBC, and analyzed its association with mutations of germline BRCA1/2 (gBRCA). Methods: We retrospectively analyze 220 patients diagnosed as advanced TNBC who were treated at the Dept. of Breast Oncology, Peking University Cancer Hospital in 2013-2018, and routinely evaluated by RECIST 1.1. Statistical analysis is performed in R 3.5.1. Cox proportional-hazard models are used for survival analysis. Results: 129 pts received non-platinum chemotherapy (NPCT) as the first-line therapy, and 91 pts received platinum-based chemotherapy (PBCT). The clinical benefit rate (CBR) and median PFS were not statistically different between NPCT and PBCT groups The median OS was 30.0 and 22.5 months for PBCT and NPCT group respectively (P = 0.09, HR = 0.70). Among them, 114 pts had BRCA gene tested, of which 14 had deleterious gBRCA mutations, 7 in each group. In PBCT group, the CBR was 85.7% and 35.1% for pts with and without deleterious gBRCA mutations respectively (P = 0.04). The median PFS, OS were 14.9 months and 5.3months (P = 0.001), 26.5 and 15.5 months (P = 0.16) for pts with and without the gBRCA mutations. No significant difference was observed between NPCT pts with and without gBRCA mutations as regards the CBR, PFS and OS. PBCT Pts had significantly more grade 3-4 anaemia (5.5% vs 0%) and thrombocytopenia (8.8% vs 0%) while higher percentage of palmar-plantar erythrodysesthesia (PPE) (12.4% vs 0%) and peripheral neuropathy (8.6% vs 1.1%) were observed in NPCT pts. Conclusions: The efficacy of platinum-based regimens as the first-line treatment of advanced TNBC insignificantly differs from that of non-platinum therapy. However, they are more effective for patients with deleterious gBRCA mutations, suggesting a BRCA1/2 genetic testing may be warranted for such patients.

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Good Tolerance of Lenalidomide Maintenance Therapy in Patients with High Risk Profile Chronic Lymphocytic Leukemia (CLL) after Frontline Chemoimmunotherapy: Preliminary Safety Overview of the CLLM1 Trial of the German CLL Study Group (GCLLSG)

Blood ◽

10.1182/blood.v124.21.4699.4699 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4699-4699 ◽

Cited By ~ 1

Author(s):

Barbara Eichhorst ◽

Jasmin Bahlo ◽

Anna Maria Fink ◽

Michael Pfreundschuh ◽

Holger Hebart ◽

...

Keyword(s):

High Risk ◽

Adverse Events ◽

Maintenance Therapy ◽

Research Funding ◽

B Cell Lymphoma ◽

First Line ◽

Skin Reactions ◽

First Line Therapy ◽

Line Therapy ◽

Grade 3

Abstract Introduction: CLL patients (pts) with persistence of minimal residual disease (MRD) after frontline chemoimmunotherapy or an unfavourable genetic profile have a high risk of early relapse and a short survival (Fink et al., Leukemia 2013). Therefore, the GCLLSG designed the CLLM1 trial, a phase 3, randomized, double-blinded, placebo-controlled study to investigate the efficacy and safety of lenalidomide maintenance therapy for high–risk (HR) CLL following first-line chemoimmunotherapy. HR is defined by the presence of MRD at levels of ≥10-2 or the combination of MRD levels of ≥10-4 to <10-2 with an unmutated IGHV status, or del(17p) or TP53 mutations. Methods and patients: Prior to randomization pts underwent central screening procedures including the assessment of all risk factors and eligibility in particular response to first-line therapy. MRD levels were centrally analyzed. Pts were randomly assigned to receive either placebo or lenalidomide 5 mg p.o. daily for the first 28-day cycle, 10 mg p.o. daily for cycle 2-6, and the target dose of 15 mg for cycle 7-12. Further escalations up to 25 mg were allowed in MRD-positive pts if the study drug was well tolerated. Pts were treated until progression. Between July 2012 and June 2014 535 pts were registered from 130 sites in five countries (Austria, Germany, Italy, Netherlands and Spain). 126 (23.6%) of the pts were excluded before proceeding to MRD-analysis after first-line therapy due to misdiagnosis of other B-cell lymphoma (N=18), withdrawal of consent (N=44), comorbidities (N=5), hepatitis B infections (N=2) or other reasons (N=57). A total of 239 pts completed the screening. 186 (77.8%) achieved MRD negativity and were therefore ineligible for the study, and 8 (3.3%) pts are awaiting randomization. Pts remained blinded for this analysis. Results: To date, 45 HR pts were randomized. First-line therapy according to investigator’s choice included FCR in 17 (37.8%), BR in 27 (60.0%) and FC in 1 (2.2%) of 45 pts. Before first-line therapy, 9 of 45 (20.0%) pts had Binet A, 19 (43.2%) Binet B and 16 (36.4%) Binet C stage of disease, respectively. The median age was 66 years (range 44-80), median CIRS score was 2 (range 0-6). 33 of 45 pts (73.3%) showed MRD levels between ≥10-4 to <10-2 combined with by high risk genetics, and 12 (26.7%) showed MRD levels ≥10-2. 43 (95.1%) pts had unmutated IGVH genes. Del(17p) was detected in 4 (8.9%) and TP53 mutation in 6 (13.3%) pts, while 2 (4.4%) pts carried both abnormalities. At the time point of analysis 195 treatment cycles [60.2% of 324 expected cycles] were documented in 26 of 45 (57.8%) randomized pts. The median number of administered cycles was 6.5 (range 1-20). 115 of 195 treatment cycles (59.0%) were administered without the occurrence of any adverse event (AE). In 80 treatment cycles (41.0%) at least one AE was documented. 133 adverse events (AEs) of all CTC grades (1 to 4) occurred in 19 of 26 pts (73.1%). Eleven pts (42.3%) experienced at least one AE of CTC grade 3 or 4. The most common AEs were related to haematological parameters [9 (34.6%) pts, 7 (26.9%) with CTC grade 3/4], infections [8 (30.7%), all CTC grade 1/2], gastrointestinal [9 (34.6%), all CTC grade 1/2], respiratory/thoracic/mediastinal [4 (15.4%), all CTC grade 1/2] and skin disorders [9 (34.6%), 2 (7.6%) with CTC grade 3]. AEs led to the discontinuation of study treatment in 3 pts (11.5%) including fatigue [N=1, CTC grade 3] and allergic dermatitis [N=2, both CTC grade 3]. In total 13 of 45 pts (28.9%) treated in both arms have discontinued the study caused by withdrawal of consent (N=5) disease progression (N=4), toxicity (N=3) and technical reasons (N=1). To date, no treatment-related death has been reported in both treatment arms. Seven SAEs have been reported so far, three of them related to treatment including septic arthritis due to staphylococcal infection, autoimmune haemolytic anemia and cholecystitis, the latter resulted in study discontinuation. Conclusion: So far, maintenance therapy with lenalidomide or placebo appears to be a safe treatment option as the majority of adverse events reported during the maintenance therapy were mild or moderate (CTC grade 1/2). Severe adverse events (CTC grade 3/4) were observed solely with skin reactions and cytopenia. Reasons for discontinuation were mostly non-serious events including skin reactions and fatigue. Later analyses will clarify the impact of lenalidomide maintenance on relapse-free survival in high-risk CLL. Disclosures Eichhorst: Roche: Research Funding; Mundipharma: Research Funding. Off Label Use: Lenalidomide is not approved for maintenance treatment in CLL. Fink:Celgene: Other. Maschmeyer:Celgene: Consultancy. Westermann:Celgene: Other. Zey:Celgene: Other. Fischer:Roche: Other. Wendtner:Celgene: Consultancy, Honoraria, Research Funding. Ghia:Merck: Consultancy; GSK, Roche Italia: Consultancy; Gilead, Pharmacyclics, Boehringer Ingelheim, Celgene, Roche Italia: Membership on an entity's Board of Directors or advisory committees. Bosch:Celgene: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding. Döhner:Celgene: Research Funding. Stilgenbauer:Celgene: Consultancy, Honoraria, Research Funding. Boettcher:Roche: Honoraria, Research Funding; Celgene: Research Funding. Hallek:Celgene: Consultancy, Honoraria, Research Funding.

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Efficacy of Mitoxantrone and Etoposide in Patients with Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy.

Blood ◽

10.1182/blood.v110.11.4385.4385 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4385-4385 ◽

Cited By ~ 1

Author(s):

Rajesh Sehgal ◽

Wassim McHayleh ◽

James Natale ◽

Anastasios Raptis ◽

Mounzer Agha ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Infectious Complications ◽

High Dose ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Grade 3 ◽

Acute Myeloid

Abstract The most effective reinduction regimen for acute myeloid leukemia (AML) patients who do not achieve complete remission (CR) after one cycle of cytarabine combined with an anthracycline is not well established. In an effort to search for new synergistic and non-cross resistant antileukemic regimens different chemotherapeutic combinations have been investigated in refractory AML patients. Multiple regimens including high dose cytarabine, anthracyclines, fludarabine and etoposide have been used with CR rates up to 40%. Mitoxantrone and etoposide have activity in AML as induction agents but their role in reinduction in patients not responding to first line therapy has not been fully established. In the current retrospective study we evaluated the efficacy and toxicity of mitoxantrone and etoposide in AML patients treated at our institution who did not respond to first induction therapy with cytarabine and an anthracycline. A total of fifty seven AML patients were treated with mitoxantrone and etoposide (mean age 55 years, range 18–75 years). Twenty four patients were treated with mitoxantrone 10 mg/m2/d and etoposide 100 mg/m2/d both administered intravenously, days 1 to 5 (regimen 5+5) and thirty three patients were treated with mitoxantrone 10 mg/m2/d administered intravenously days 1 to 3 and etoposide 100 mg/m2/d administered intravenously, days 1 to 5 (regimen 3+5). Twenty six of fifty seven patients (46%) achieved CR. CR was achieved in 38% of patients (9/24) treated with the 5+5 regimen and 52% of patients (17/33) treated with the 3+5 regimen. Mean blast percentage before treatment with mitoxantrone and etoposide was 25% in patients who achieved CR vs 40% in patients who did not achieve CR (p < 0.03). Grade 3/4 hepatic toxicities were seen in 5% (3/57) of patients and there were no grade 3 or 4 renal toxicities. The median duration of neutropenia in patients achieving CR was 29 days after reinduction. 10% (6/57) of the patients died from infectious complications. Cytogenetic analyses were performed prior to first-line therapy in all patients. Patients with favorable cytogenetics treated with etoposide and mitoxantorne had 100% CR (3/3), patients with standard cytogenetics had 58% CR (19/33) and patients with unfavorable cytogenetics had 19% CR (4/21). Overall CR was achieved in 61% (22/36) of patients with favorable and standard cytogenetics. Our data suggest that the combination of etoposide and mitoxantorne is an active and well tolerated regimen, especially in patients with favorable and standard cytogenetics, and warrants further studies in prospective trials.

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Tolerability of a weekly schedule of docetaxel-cisplatin as first-line treatment in patients with stage IIIB/IV non-small cell lung cancer (NSCLC)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17112 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17112-17112

Author(s):

D. Binder ◽

M. Hackenthal ◽

L. Graseck ◽

H. Schweisfurth ◽

C. Schäper ◽

...

Keyword(s):

Locally Advanced ◽

Tumour Response ◽

Low Frequency ◽

Neutropenic Fever ◽

Hematologic Toxicity ◽

Weekly Schedule ◽

Line Treatment ◽

First Line ◽

Grade 3 ◽

First Line Treatment

17112 Background: Recent trials have shown that the combination docetaxel-cisplatin is an effective first-line treatment in locally advanced or metastatic NSCLC. However, the regimen can be associated with a marked rate of neutropenia. The present study tests the efficacy and tolerability of a weekly schedule of docetaxel and cisplatin. Methods: Patients (pts) with histologically confirmed NSCLC stages UICC IIIB (malignant effusion) or IV were treated with docetaxel (35 mg/m2, 30 min. infusion) and cisplatin (25 mg/m2, 30 min. infusion) on days 1, 8 and 15 repeated every 4 weeks for 4 to 6 cycles. This phase II study is scheduled to include 50 pts and primary endpoint is tumour response rate. Pts received 8 mg of ondansetron and 8 mg of dexamethasone i.v. preceding every day of therapy and oral dexamethasone 2 × 4 mg from the day before until the day after chemotherapy. NK1-antagonists were given at discretion of the investigator. In total, 2750 ml of volume were infused on each day of therapy. Most of the pts were treated in an outpatient department. Safety was assessed via common terminology criteria for adverse events v3.0 (CTCAE 3.0). Interim tolerability data is presented. Results: Currently, 28 pts were evaluable for this interim tolerability analysis. Pts received a median of 3 full cycles. There were no treatment-related deaths. Dose reductions of docetaxel and cisplatin due to poor tolerability were necessary in 3 pts (11%). No pts suffered from neutropenic fever while grade 3 neutropenia occurred in only 2 pts (7%). There was no grade 2/3/4 thrombocytopenia. 5 pts (18%) had grade 2 anemia, and 2 pts (7%) had an elevation of the plasma creatinine (both grade 1). Other toxicities were non-neutropenic infections (5/1/1 pts with grade 2, 3, 4, respectively), diarrhea (3 pts [11%] with grade 3), constipation (5 pts [18%] with grade 2) and mucositis (4 pts [14%] with grade 2/3). There was no grade 3/4 nausea or vomiting; 3 pts [11%] had grade 2 nausea/vomiting. Conclusions: In the present study, the combination of docetaxel and cisplatin appears well tolerated. It was associated with a very low frequency of severe hematologic toxicity or neutropenic fever. With relatively low hydration volumes it can be safely administered in an outpatient setting. [Table: see text]

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Pembrolizumab (MK-3475) plus 5-fluorouracil (5-FU) and cisplatin for first-line treatment of advanced gastric cancer: Preliminary safety data from KEYNOTE-059.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.161 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 161-161 ◽

Cited By ~ 4

Author(s):

Charles S. Fuchs ◽

Atsushi Ohtsu ◽

Josep Tabernero ◽

Eric Van Cutsem ◽

Jiang Dian Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Gastroesophageal Junction ◽

Safety Data ◽

Line Treatment ◽

First Line ◽

Prior Therapy ◽

First Line Therapy ◽

Grade 3 ◽

First Line Treatment

161 Background: Standard first-line treatment for advanced gastric cancer includes combination chemotherapy with a platinum agent and a fluoropyrimidine. The anti–PD-1 humanized monoclonal antibody pembrolizumab (pembro) has shown promising antitumor activity as monotherapy in patients (pts) with advanced gastric cancer. We report preliminary safety data for pts with advanced gastric cancer treated with pembro + cisplatin and 5-FU in the multicohort, phase 2 KEYNOTE-059 study (NCT02335411). Methods: Eligible pts were aged ≥ 18 y and had HER2– relapsed or metastatic gastric or gastroesophageal junction adenocarcinoma, ECOG PS 0-1, and no prior therapy for metastatic disease. Pts received pembro 200 mg + 5-FU 800 mg/m2 (or capecitabine 1000 mg/m2 in Japan) + cisplatin 80 mg/m2 Q3W for 6 cycles followed by pembro + 5-FU for up to 2 y or until confirmed progression, intolerable toxicity, or investigator decision. Primary end point was safety and tolerability of the combination. Results: Of the 17 pts enrolled (10 from Asia, 7 from outside Asia), 70.6% were men, and median age was 58.0 y. Three pts (17.6%) had a prior gastrectomy—2 total, 1 partial. As of the Aug 12, 2015, data cutoff date, median follow-up duration was 3.6 mo (range 2.6-5.4), and pts received a median of 5 treatment cycles (range 3-7). Only 1 pt (5.9%) discontinued treatment (due to progressive disease). There were no treatment-related deaths or discontinuations. Twelve pts (70.6%) experienced treatment-related adverse events (AEs) of any grade, most commonly neutropenia/decreased neutrophils (n = 7, 41.2%), stomatitis (n = 6, 35.3%), and decreased appetite (n = 5, 29.4%). Eight pts (47.1%) experienced ≥ 1 grade 3-4 treatment-related AE; only neutropenia/decreased neutrophils (n = 4 [23.5%] grade 3, n = 3 [17.6%] grade 4) occurred in > 1 pt. AEs of interest based on immune etiology, regardless of attribution by investigator, were grade 2 infusion-related reaction and grade 2 pruritus (n = 1 [5.9%] each). Conclusions: Preliminary data from KEYNOTE-059 suggest the combination of pembro, cisplatin, and 5-FU has a manageable safety profile as first-line therapy in pts with advanced gastric cancer. Clinical trial information: NCT02335411.

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Progression-free survival as a predictor of overall survival in patients with advanced breast cancer: A real-world study from the China National Cancer Center.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e12590 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e12590-e12590

Author(s):

Hongnan Mo ◽

Binghe Xu ◽

Fei Ma ◽

Qing Li ◽

Pin Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Real World ◽

Progression Free Survival ◽

Advanced Breast ◽

Line Treatment ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

First Line Treatment

e12590 Background: Use of progression-free survival (PFS) as a clinical trial endpoint in first-line treatment of patients with advanced breast cancer is attractive, but would be enhanced by establishing a correlation between PFS and overall survival (OS). Methods: From January 2003 to December 2012, 1851 patients with advanced breast cancer at start of first-line therapy were enrolled in this real-world study. An independent cohort of patients hospitalized in 2013 was used for external validation. All data were collected from the Database of China National Cancer Cancer. Results: The correlation coefficient (Pearson’s r) between PFS and OS was 0.807 in patients only receiving endocrine therapy as first-line treatment, 0.643 in those treated with chemotherapy, and 0.642 in the whole cohort. Receiver operating characteristic curve indicated that PFS = 12 months was the optimal cutoff value for predicting patient’s survival. The median OS was 30.0 months (95% CI 27.8-32.2) in the PFS < 12 months group, and 69.0 months (95% CI 60.8-77.2) in the other group (P < 0.0001). Multivariate analysis revealed that compared with patients who did not progress at 12 months, the adjusted hazard ratio (HR) for death was 2.681 (95% CI, 2.301-3.124; P < 0.0001) for patients with PFS < 12 months. Subgroup analysis based on patient’s age, molecular subtype, visceral metastasis and types of first-line treatment further confirmed that PFS < 12 months was associated with significant poor prognosis in all these subgroups. In patients with luminal type of breast cancer, the HR for death was 2.567 (95%CI 2.147-3.069; P < 0.0001) for patients with PFS < 12 months. Notably, for these patients with luminal type breast cancer who had progressed within 12 months after first-line treatment, addition of chemotherapy in the second-line therapy would surprisingly have adverse effects on patients’ survival when compared with endocrine therapy alone (HR = 1.627, 95%CI 1.016-2.604, P = 0.043). The findings were externally validated in the independent cohort. Conclusions: To our knowledge, this is the first real-world study revealed that PFS at 12 months in first-line therapy predict OS of patients with advanced breast cancer.

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A double-blind, randomized placebo-controlled, phase II study of maintenance enzastaurin (ENZ) with 5-FU/leucovorin (LV) plus bevacizumab (BV) following first-line therapy for metastatic colorectal cancer (mCRC).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.501 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 501-501 ◽

Cited By ~ 1

Author(s):

R. A. Wolff ◽

W. Schepp ◽

M. DiBartolomeo ◽

A. Hossain ◽

C. Stoffregen ◽

...

Keyword(s):

Maintenance Therapy ◽

Disease Progression ◽

Phase Ii ◽

Phase Ii Study ◽

Locally Advanced ◽

First Line ◽

Antitumor Effects ◽

First Line Therapy ◽

Line Therapy ◽

Grade 3

501 Background: Maintenance therapy is designed to maximize progression-free survival (PFS) and minimize toxicity in advanced CRC. ENZ is an oral serine/threonine kinase inhibitor that targets PKC-b and the AKT/PI3K pathway. Preclinical studies demonstrated synergistic antitumor effects when ENZ was combined with BV. In phase I studies, the combination was well tolerated. This phase II study assessed ENZ with 5-FU/LV plus BV as maintenance therapy for mCRC. Methods: Patients had locally advanced or mCRC, and completed 6 cycles of first-line chemotherapy ≤4 wks prior to randomization. Arm A received a loading dose of ENZ 1,125 mg, followed by 500 mg/d subsequent doses. Arm B received placebo. Both groups received 5-FU/LV (LV 400 mg/m2 IV, 5-FU 400 mg/m2 bolus, 5-FU 2,400 mg/m2 IV) plus BV 5 mg/kg IV, every 2 wks. Patients were treated with 5-FU/LV plus BV plus either ENZ or placebo until disease progression or for 1 yr. Primary endpoint was PFS from randomization. Secondary endpoints were overall survival (OS) from randomization, and OS and PFS from start of first-line therapy. Analysis was done after 50 events (objective or clinical progression). Results: 58 patients were randomized to Arm A (57 treated), 59 to Arm B (58 treated). 82 (70.1%) patients discontinued treatment (Arm A, 42 [72.4%]; Arm B, 40 [67.8%]), the majority due to disease progression. Median cycles were 9 in Arm A, 10 in Arm B. Median PFS in months was 5.8 in Arm A and 8.1 in Arm B (hazard ratio [HR]=1.35, 95% CI: 0.84, 2.16; protocol specified one-sided test, p=0.896). Median OS was not calculable due to high censoring (77.6% in Arm A and 91.5% in Arm B). Median PFS in months from start of first-line therapy was 8.9 in Arm A and 11.3 in Arm B (HR=1.39, 95% CI: 0.86, 2.23; one-sided, p=0.913). More patients developed thrombosis or embolism (TE), including pulmonary embolism, on Arm A (5 [8.8%] patients had grade 3 and 5 [8.8%] grade 4 TE) compared with Arm B (no grade 3 and 1 [1.7%] grade 4 TE). Conclusions: ENZ did not demonstrate an advantage in PFS compared to BV-based therapy alone. Further development of maintenance therapy with ENZ is not recommended for mCRC. [Table: see text]

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Cetuximab maintenance therapy in unresectable metastatic colorectal cancer patients with wild-type RAS and BRAF: A single-center retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15004 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15004-e15004

Author(s):

Tao Jiang ◽

Xiaoyan Lin ◽

Hao Chen ◽

Jianwei Zhen ◽

Bin Du ◽

...

Keyword(s):

Maintenance Treatment ◽

Observation Group ◽

Line Treatment ◽

Single Center ◽

Wild Type ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Line Therapy ◽

First Line Treatment

e15004 Background: Cetuximab plus FOLFIRI (leucovorin, fluorouracil and irinotecan) is preferred first line therapy for RAS and BRAF wild-type (RBWT) metastatic colorectal cancer (mCRC) patients. However, the side effects often require dose-reductions or discontinuation calling for maintenance strategies to reduce toxicity and preserve efficacy. Therefore, we evaluated efficacy and safety of cetuximab maintenance therapy after first-line treatment in unresectable mCRC patients with RBWT. Methods: This single center, retrospective study enrolled patients (aged 18-71 years) with untreated mCRC with RBWT, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, with at least one measurable lesion according to response evaluation criteria in solid tumor (RECIST). All patients received first line cetuximab plus FOLFIRI every two weeks for 9-12 cycles, after which, patients with treatment response chose to either enter observation (stop treatment) or maintenance 1 (cetuximab plus irinotecan) group. After 6-12 cycles of maintenance 1, patients with treatment response entered maintenance 2 (cetuximab only). If patients progressed on maintenance 2, reintroduction of cetuximab plus FOLFIRI was suggested. Primary endpoint was failure-free survival (FFS); while secondary endpoints included disease control rate (DCR), objective remission rate (ORR) and progression free survival (PFS). Safety events were also evaluated. Results: Among 62 enrolled patients, 56 patients completed first-line treatment (DCR: 90.3%, ORR: 62.9%) and 30 patients entered maintenance 1 [median PFS1 (mPFS) =6.1 months, 95%CI: 6.0-6.2, DCR=60%, ORR=30%]. Of these, 18 entered maintenance 2 [mPFS2=6.6 months, 95%CI: 5.1-8.1, DCR=27.8%, ORR=5.6%]. The mFFS was significantly longer in maintenance 1 (12.8 months, 95%CI: 10.8-14.8) compared to observation group (3.0 months; hazard ratio [HR]: 0.21, 95%CI: 2.6-3.4, P<0.001). Overall mFFS was 19.0 (95%CI: 11.0-27.0) in maintenance and 9.5 months in observation group (HR: 0.195, 95%CI: 7.4-11.6; P<0.001). Rash acneiform, mucositis and asthenia were the common adverse events observed during maintenance treatment. Conclusions: Maintenance treatment with cetuximab after first line therapy significantly improved FFS, with acceptable safety profile in untreated mCRC RBWT patients.

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Genetic Aberrations and Response to Fludarabine as First Line Treatment in a Serie of B-CLL Patients.

Blood ◽

10.1182/blood.v106.11.2131.2131 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2131-2131

Author(s):

Pilar Giraldo ◽

Araceli Rubio-Martinez ◽

Valle Recasens ◽

Mikel Valganon ◽

Paz Latre ◽

...

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Genetic Alterations ◽

Fisher Exact Test ◽

Line Treatment ◽

First Line ◽

Genetic Aberrations ◽

First Line Therapy ◽

Line Therapy ◽

First Line Treatment

Abstract Background: Genetic factors have been established in the recent years as the most important independent predictors of disease progression and survival in patients with B-chronic lymphocytic leukaemia (B-CLL). Fludarabine is an approved first-line treatment for B-CLL, which achieves superior remission rates than traditional therapies. The drug is equally effective in early and advanced disease and in younger and elderly patients with B-CLL but different results have been found in patients with cytogenetic aberrations as methylation in the TP53 promoter Aims: To evaluate the response to Fludarabine as first-line therapy in B-CLL patients with advanced stages. Patients and methods: In the study 55 B-CLL patients were enrolled. The diagnosis was established based on standard morphologic and immunophenotypic criteria, and classified on high clinical risk category Rai stage III/IV treated with Fludarabine (25 mg/m2 daily for 5 days IV in a 28-day cycle) as first-line therapy from January 00 to December 03. Response was evaluated after 4 cycles of therapy and in those patients which had not achieved complete remission (CR) two additional cycles were administrated. Criteria for response were established using the revised 1996 NCIWG. FISH studies were performed using the probes LSI p53 (17p13), LSI D13S25 (13q14), CEP 12 and ATM gene (11q22). The sequences of the IGVH genes were determined in cDNA of the patients. Responses to therapy, time to progression disease and overall survival were available to analyse in 41 patients. Association was studied using contingence tables followed by Fisher exact test and to evaluate survival by acturial method of Kaplan Meier and Cox regression. Results: Mean age 64 (36.9–83.9), female 53.7%. 75% of patients presented genetic aberrations associated with worse prognosis: del (17p) and/or del (11q) (45%). No-mutated IGVH genes (57%). Response: 83.5% of patients achieved response (CR 47.8%). Related to genetic aberrations the responses were: 55.5% in patients with del(17p), 75.0% del(11q), 100% +12, 88.8% del(13q) and 100% of patients without genetic alterations showed response to Fludarabine. The 48.8 % of patients developed progression of disease with mean duration of the response of 15.1 months. Related to genetic aberrations the progression was over 81% of patients with genetic aberrations versus 55.5% without genetic alterations (p=0.044). The overall survival was 68.0 months. 34.1% of patients are alive in CR, 36.6% are alive with stable disease 7.3 % are alive with disease in progression and 22.0 % have died. Conclusions: A high response to Fludarabine in first line therapy was observed, however only 55.5% of patients with del(17p) showed response. Patients with genetic aberrations had higher significant rate of progression in comparison with those containing normal genotypes.

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A Decade Of Imatinib As First-Line Treatment Of Chronic Myeloid Leukemia: A Single - Latin American Institution Experience

Blood ◽

10.1182/blood.v122.21.5194.5194 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5194-5194

Author(s):

Alvaro Cabrera Garcia ◽

Carolina Balderas Delgado ◽

Juan Julio Kassack Ipiña ◽

Christian Omar Ramos Peñafiel ◽

Juan Collazo Jaloma ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Latin American ◽

Myeloid Leukemia ◽

Chronic Phase ◽

Hematologic Toxicity ◽

Line Treatment ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Eutos Score

Abstract Targeted therapy commenced against Chronic Myeloid Leukemia (CML) with the development of small-molecule tyrosine kinase inhibitors (TKIs), since its approval in 2001 as first-line therapy, imatinib has been effective in achieving high response rates and improving the prognosis. However, the excellent results of large clinical trials are not entirely reproducible in the “real world”, we want to share our experience of a decade of use as front-line treatment. A total of 160 patients with previously untreated CML since 2002 were reviewed: 90% chronic phase (CP), 7% accelerated phase (AP), and 3% blast phase (BP). All were treated with standard-dose imatinib. In CP, overall survival (OS) at 75 months was 82% and progression-free survival 66%(PFS). Survival was worse in those over 60 years (P= < .001). 40% achieved and maintained Complete Cytogenetic Response (CCyR), 19 patients progressed to BP. 23.4% had some degree of hematologic toxicity that required a temporary suspension or reduction of the initial dose. 26.8% of patients with chronic phase treated at our institution were in the high EUTOS score. In this population, the EUTOS score was not predictive for outcome. Our study showed that imatinib is effective, and well tolerated by our patients and remains as a good strategy used as first-line therapy for patients with CML. Disclosures: No relevant conflicts of interest to declare.

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