Clinical Outcome of an Multicentre, Randomized, Phase II Clinical Trial for Patients with Extranodal NK/T Cell Lymphoma Treated By P-Gemox or Aspametdex

Intruduction Extranodal natural killer/T-cell lymphoma (ENKTL) is an uncommon, aggressive form of non-Hodgkin's lymphoma. Optimal therapeutic strategies have not been fully defined yet. Nasal NK/T-cell lymphomas present mostly with stage I/II disease. For stage I/II nasal lymphoma, a combination of chemotherapy and radiotherapy yields optimal results. Concomitant chemoradiotherapy and sequential chemotherapy and radiotherapy give similar response rates and survivals. For stage III/IV nasal, nonnasal, and disseminated ENKTL, systemic chemotherapy is indicated. Conventional anthracycline-based regimens are ineffective. Regimens containing L-asparaginase are most effective. Both AspaMetDex and P-Gemox is recommended as major effective combined chemotherapy regimen by NCCN guideline. Therefore, we try to evaluate the efficacy and toxicity for P-Gemox plus thalidomide and AspaMetDex followed by extensive involved field radiotherapy (EIFRT) as first-line treatment for newly diagnosed stage I/II patients and as salvage regimen for newly diagnosed stage III/IV or relapsed/refractory ENKTL in this clinical study. Methods We initiated a prospective, multicentre, randomized, phase II clinical trial at 12 centers in China at March 2014. Patients were randomly assigned to receive either P-Gemox+thalidomide regimen (Group A: Pegaspargase 2000U/m2; im d1, Gemcitabine 1000mg/m2; ivdrip , d1, d8. Oxaliplatin 130mg/m2; ivdrip, d1, thalidomide 100mg/d po, for one year.) or AspaMetDex regimen ( Group B: Pegaspargase 2000U/m2; im, d1, Methotrexate 3000mg/ m2; civ 6-hour, d1, calcium folinate 30mg iv, q6h, until reach safe serum MTX concentration, Dexamethasone 40mg/d ivdrip, d1-4.). For newly diagnosed stage I/II patients, both regimens were repeated every three weeks for a maximum four cycles as induction chemotherapy and followed by EIFRT at the dosage of 56Gy in 28 fractions over 4 weeks. Primary EIFRT was delivered using 6-MeV linear accelerator using 3-dimensional conformal treatment planning. For newly diagnosed stage III/IV or relapsed/refractory ENKTL, the regimens were repeated every three weeks for a maximum six cycles. Patients underwent autologous hematopoietic stem cell transplantation (ASCT) as consolidation if they achieved response (complete remission,CR or partial remission,PR). The primary endpoint was progression-free survival(PFS). Results Between March 2014 and March 2018, 165 patients were randomly assigned. 85 patients to Group A, 80 patients to Group B. 156 patients were evaluable for response. Investigator-assessed overall response at the end of induction was 88.2% in the Group A and 75.0% in the Group B. Complete remission (CR) rate were 60.0% and 55.0%. Among 107 newly diagnosed stage I/II patients, 54 patients were assigned to Group A (52 assessed), and 53 to Group B (47 assessed). Overall response during induction in Group A and B was similar in both groups, were 64.8% and 64.2%. 58 newly diagnosed stage III/IV or relapsed refractory patients were enrolled. 31 patients were assigned to Group A (30 assessed), and 27 to Group B. The efficacy rate of Group A was higher than that of Group B. Overall response rate were 87.1% and 66.6%, respectively. At median follow-up of 24.6 (1.0-60.9)months, 3-year progression-free survival (PFS) and overall survival (OS) of whole cohort were 61.4% and 63.4%. PFS and OS rate of Group A were similar to Group B(Figure 1). Group B was better tolerated than Group A, with lower rates of agranulocytosis, thrombocytopenia and infections. While anemia,hyperbilirubinemia, edema, and increased BUN/Cr were more common in Group B. Three patients died of treatment related toxicity only in Group B . Two patients died of severe acute renal failure and sepsis at the first cycle, and one patient died of sepsis at the third cycle. CONCLUSION: Induction chemotherapy of both P-Gemox+Thalidomide and AspaMetDex regimen followed by EIFRT yielded promising efficacy for patients with stage I/II ENKTL. There is little difference therapeutic effect between the two regimens. For advanced or relapsed patients, both regimen showed unsatisfied survival outcome. Meanwhile, P-Gemox+ Thalidomide was less toxic with more convenient administration in outpatients clinics in comparison to AspaMetDex. ( ClinicalTrials.gov, NCT 2085655 ). Disclosures Li: Guangdong Province Hospital: Employment.

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Randomized Phase II Study of Temozolomide and Radiotherapy Compared With Radiotherapy Alone in Newly Diagnosed Glioblastoma Multiforme

Journal of Clinical Oncology ◽

10.1200/jco.2005.00.331 ◽

2005 ◽

Vol 23 (10) ◽

pp. 2372-2377 ◽

Cited By ~ 167

Author(s):

Helen Athanassiou ◽

Maria Synodinou ◽

Evagelos Maragoudakis ◽

Mihalis Paraskevaidis ◽

Cosmas Verigos ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Study ◽

Malignant Gliomas ◽

Progression Free Survival ◽

Combined Modality Treatment ◽

Newly Diagnosed ◽

Randomized Phase Ii ◽

Group A ◽

One Year ◽

Group B

Purpose Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM. Patients and Methods One hundred thirty patients with pathologically confirmed, newly diagnosed GBM were randomly assigned (110 assessable patients) to receive either TMZ 75 mg/m2/d orally, concomitantly with RT (60 Gy in 30 fractions; group A, n = 57), followed by six cycles of TMZ (150 mg/m2 on days 1 through 5 and 15 to 19 every 28 days), or RT alone (60 Gy in 30 fractions; group B, n = 53). Results Median time to progression was 10.8 months in group A and 5.2 months in group B (P = .0001). One-year progression-free survival rate was 36.6% in group A and 7.7% in group B. Median overall survival (OS) time was also significantly better in group A versus group B (13.4 v 7.7 months, respectively; P < .0001), as was the 1-year OS at 56.3% v 15.7% (P < .0001), respectively. Toxicity was mainly hematologic. One patient with grade 4 myelotoxicity died as a result of sepsis. The other side effects were mild. Conclusion TMZ combined with RT (concomitantly and sequentially) seems to be more effective than RT alone in patients with newly diagnosed GBM. The combined-modality treatment was well tolerated.

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Pegaspargase Plus Gemcitabine, Oxaliplatin(P-Gemox) and Thalidomide Versus Aspermetdex Regimen for the Patients with Early or Advanced/Relapsed Extranodal Natural Killer/T Cell Lymphoma: Interim Analysis of a Prospective,Multicenter, Randomized, Phase III Non-Inferiority Clinical Trial

Blood ◽

10.1182/blood.v128.22.1819.1819 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1819-1819

Author(s):

Yan Gao ◽

Huiqiang Huang ◽

Yujing Zhang ◽

Hang Su ◽

Xiaoxiao Wang ◽

...

Keyword(s):

Clinical Trial ◽

Stage I ◽

Phase Iii ◽

Stage Iii ◽

Newly Diagnosed ◽

Natural Killer T Cell ◽

Group A ◽

Group B ◽

Killer T Cell

Abstract Backgroud and Purpose Extranodal natural killer/T-cell lymphoma (ENKTL) is an uncommon, aggressive form of non-Hodgkin's lymphoma. Optimal therapeutic strategies have not been fully defined yet. Both AsperMetDex and P-Gemox is recommended as major effective regimen by 2016 NCCN guideline. Therefore, we try to evaluate the efficacy and toxicity for P-Gemox plus thalidomide and AsperMetDex followed by EIFRT as first-line treatment for newly diagnosed stage I/II patients and as salvage regimen for newly diagnosed stage III/IV or relapsed/refractory ENKTL in this study. Patients and methods We initiated a prospective, multicentre, randomized, phase III ,non-inferiority clinical trial at 12 centers in China at March 2014. Patients were randomly assigned to receive either P-Gemox+thalidomide regimen (Group A: Pegaspargase 2000U/m2; im d1, Gemcitabine 1000mg/m2; ivdrip , d1, d8. Oxaliplatin 130mg/m2; ivdrip, d1, thalidomide 100mg/d po, for one year.) or AsperMetDex regimen(Group B: Pegaspargase 2000U/m2; im, d1, Methotrexate 3000mg/ m2; civ 6-hour, d1, calcium folinate 30mg iv, q6h, until reach safe serum MTX concentration, Dexamethasone 40mg/d ivdrip, d1-4.). For newly diagnosed stage I/II patients, both regimens were repeated every three weeks for a maximum four cycles as induction chemotherapy and followed by EIFRT at the dosage of 56Gy in 28 fractions over 4 weeks. Primary EIFRT was delivered using 6-MeV linear accelerator using 3-dimensional conformal treatment planning. For newly diagnosed stage III/IV or relapsed/refractory ENKTL, the regimens were repeated every three weeks for a maximum six cycles. Patients underwent autologous hematopoietic stem cell transplantation (ASCT) as consolidation if they achieved response (complete remission, CR or partial remission, PR). The primary endpoint was progression-free survival(PFS), with a non-inferiority margin of 15%. Results 110 patients were enrolled (56 patients in Group A, 54 in Group B) and 96 patients were evaluable for response. Among 63 newly diagnosed stage I/II patients, 32 patients were assigned to Group A (27 assessed), and 31 to Group B (27 assessed). At median follow-up of 13.5 months (IQR 0.5¨C27.5), 2-year PFS were 82.9%(95%CI:17.574-24.111) and 84.5% (95%CI:18.849- 25.688). 2-year OS were 95.0%(95%CI:13.023-22.896) and 75.8%(95%CI:11.647-21.269), P=0.089, (Figure1). CR rate of both group were all 59.3%(16/27), and objective response rate(ORR) were 85.2%(23/27) and 81.5%(16/27), respectively. After EIFRT, ORR of Group A increased to 92.6% (25/27), CR rate was 88.8% (24/27). ORR of Group B increased to 88.8% (24/27), CR rate was 85.1% (23/27). For 47 newly diagnosed stage III/IV or relapsed/refractory patients, 24 patients were assigned to Group A (22 assessed) and 23 to Group B (20 assessed). At median follow-up of 14.5 months (IQR 0.6¨C28.1), median PFS was longer in the Group A than Group B(12.2 vs. 7.6 months, P=0.365). 2-year OS were 52.5%(95%CI:13.023-22.896) and 48.9% (95%CI:11.647- 21.269), P=0.935 (Figure2). The ORR were 86.4%(19/22) and 70%(14/20), respectively. CR rate were similar for both group with 50%. Six cases (3 cases in each group ) had received ASCT after response, 3 patients relapsed in 6 months after ASCT(2 cases in group A, 1 case in group B) , 2 patients died of disease progression. Group B was better tolerated than Group A, with lower rates of agranulocytosis, thrombocytopenia and infections. While anemia, hyperbilirubinemia, edema, and increased BUN/Cr were more common in Group B. Three patients died of treatment related toxicity only in Group B. Two patients died of severe acute renal failure and sepsis at the first cycle, and one patient died of sepsis at the third cycle (Table 1). Median hospitalization time were 1.9 days for Group A and 4.9 days for Group B(P<0.01), respectively. CONCLUSION: Induction chemotherapy of both P-Gemox+Thalidomide and AsperMetDex regimen followed by ENKTL yielded promising efficacy for patients with stage I/II ENKTL. For advanced or relapsed patients, both regimen showed unsatisfied survival outcome. Meanwhile, P-Gemox+ Thalidomide may be less toxic with more simple and convenient administration in outpatients clinics in comparison to AsperMetDex. This clinical trial is still ongoing . (ClinicalTrials.gov, NCT 2085655). Funding: 5010 Program for Clinical Research , Sun Yat -Sen University. Disclosures No relevant conflicts of interest to declare.

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Induction (Ind) plus concurrent (Con) chemotherapy with high-dose (74 Gy) 3-dimensional (3-D) thoracic radiotherapy (TRT) in stage III non-small cell lung cancer (NSCLC): Preliminary report of Cancer and Leukemia Group B (CALGB) 30105

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7042 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7042-7042 ◽

Cited By ~ 5

Author(s):

A. W. Blackstock ◽

M. A. Socinski ◽

J. Bogart ◽

L. Gu ◽

X. Wang ◽

...

Keyword(s):

Progression Free Survival ◽

Standard Of Care ◽

Stage Iii ◽

High Dose ◽

Free Survival ◽

3 Dimensional ◽

Randomized Phase Ii ◽

Group B ◽

Leukemia Group

7042 Background: Combined chemoradiotherapy is the standard of care in stage III NSCLC. At standard TRT doses, local failures remain problematic and strategies exploiting the dose-response aspect of TRT are warranted. 3-D TRT allows escalation of TRT dose with acceptable toxicity (Socinski et al, J Clin Oncol 22:4341, 2004) and may enhance survival by improving loco-regional control. Methods: This is a two-arm randomized phase II trial evaluating 74 Gy with Con chemotherapy: Arm A- 2 cycles of Ind carboplatin (C) (AUC 6) and paclitaxel (P) (225 mg/m2) followed by weekly Con C (AUC 2/wk) and P (45 mg/m2) and 74 Gy; Arm B- 2 cycles of Ind C (AUC 5) and gemcitabine (G) (1000 mg/m2 d1,8) followed by Con G (35 mg/m2 twice weekly) and 74 Gy. The primary endpoint was a survival rate of ≥50% at 18 months after treatment initiation or med survival time (MST) of ≥18 mos. Results: 69 pts were entered (43 Arm A, 26 Arm B)- med age 61 yrs (39–77), 77% male, PS 0:1 42%:58%, stage IIIA:B 52%:48%. Ind therapy on both arms was well tolerated with no pts experiencing disease progression. ARM A- Overall response rate (RR) to all therapy was 61.9%. Gr 3–4 toxicities during Con therapy were anemia (15%), neutropenia (26%), esophagitis (9%), fatigue (9%), neuropathy (3%) and pulmonary (12%). There was 1 (3%) Gr 5 cardiac event. With med follow-up of 16.4 mos, the med progression-free survival (PFS) is 15.2 mos. The MST is not mature enough to estimate as only 15 deaths have occurred. ARM B- Closed early due to 3 (13%) Gr 5 pulmonary events. Overall RR to all therapy was 66.6%. Gr 3–4 toxicities during Con therapy were anemia (13%), fatigue (35%), esophagitis (35%), hemoptysis (4%), pulmonary (26% plus the 3 Gr 5 events). With med follow-up of 22 mos, the med PFS is 7.7 mos and the MST is 13.9 mos. There was a correlation between Gr 3–5 pulmonary toxicity and V20 ≥ 38% (p<0.05). Conclusions: 1) High dose 3-D TRT is feasible within CALGB, 2) the details of TRT (V20) are important with regard to toxicity, 3) the survival of pts on Arm A appears promising. [Table: see text]

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Thalidomide Based Regimens (TBR) for Relapsed/Refractory Multiple Myeloma Patients: Long Term Follow Up, Unmaintained Remissions and Disease Control after Subsequent Treatments.

Blood ◽

10.1182/blood.v110.11.4812.4812 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4812-4812

Author(s):

Maria Roussou ◽

Efstathios Kastritis ◽

Athanasios Anagnostopoulos ◽

Evangelos Eleftherakis-Papaiakovou ◽

Charis Matsouka ◽

...

Keyword(s):

Multiple Myeloma ◽

Progression Free Survival ◽

Free Survival ◽

Refractory Multiple Myeloma ◽

Long Term Follow Up ◽

Group A ◽

Pulse Dexamethasone ◽

Group B

Abstract Introduction: The effectiveness of thalidomide based regimens (TBR) in patients with relapsed/refractory multiple myeloma is well established. However, there are still limited data regarding the long term follow up after such regimens and the outcome of patients when they progress and they receive further treatment. In order to answer these questions we evaluated a series of 114 patients with relapsed/refractory multiple myeloma who were treated with TBR. None of these patients had previously received thalidomide, bortezomib or lenalidomide. Patients and Methods: All patients were treated with thalidomide and dexamethasone with or without other oral agents. More specifically 41 patients had received continuous thalidomide and pulse dexamethasone, 25 patients clarithromycin, continuous thalidomide and pulse dexamethasone, 43 patients intermittent thalidomide, pulse dexamethasone and cyclophosphamide and 5 patients continuous thalidomide, pulse dexamethasone and cyclophosphamide. Type of treatment at the time of progression after TBR, response to this treatment and progression free survival were recorded for each patient. Moreover, patients who received novel agents after progression to TBR, were divided into 2 subgroups, according to their resistance to thalidomide. In group A, patients had refractory or progressive myeloma while on TBR or within 2 months after discontinuation of TBR. In group B, myeloma progressed more than 2 months after discontinuation of TBR. Results: Among the 114 patients, 41 had not responded to TBR and 73 (64%) had achieved at least a partial response. The median PFS for all patients was 8 months. As of June 2007, 10 patients remain without progression from 28 to 81 months (median 54 months). Eight patients remain off treatment and without progression for a median of 56 months (range 28–81). Patients who did not respond to or progressed after TBR were analyzed for further treatment and outcome. Thirty eight patients (37%) died before receiving further treatment, 23 patients (23%) received conventional chemotherapy and 41 patients (40%) received continuous thalidomide and dexamethasone +/− clarithromycin or cyclophosphamide (17 patients), bortezomib and dexamethasone (7 patients), melphalan-bortezomib-dexamethasone and intermittent thalidomide (12 patients) or lenalidomide with dexamethasone (5 patients). Among these 41 patients, 24 were classified in group A (thalidomide resistant) and 17 in group B. Overall 17 (41%) achieved at least partial response after retreatment with novel agent-based regimens. A response was observed in 46% of patients in group A and in 35% of patients in group B. The median progression free survival of the 41 patients who received retreatment with novel agents was 9.2 months and the median survival was 17 months. Among the 23 patients who received conventional chemotherapy only five (21%) patients responded and the progression free survival and the median survival were 5.3 and 10.2 months, respectively. Conclusions: After an oral TBR regimen 6 (5%) patients remain without treatment and free of progression for more than 4 years. A significant number of patients who progressed after TBR and who received further treatment which included a novel agent achieved a response, including several patients who were resistant to TBR.

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Characteristics and outcomes of extranodal NK/t-cell lymphoma (ENKL): A North American (NA) multi-institutional experience.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.8060 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 8060-8060

Author(s):

Lauren Shizue Maeda ◽

Jessica L. Geiger ◽

Kerry J. Savage ◽

Jim Rose ◽

Lauren C. Pinter-Brown ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Early Stage ◽

Combined Modality Therapy ◽

Progression Free Survival ◽

T Cell Lymphoma ◽

Stage I ◽

Stage Iii ◽

Cell Transplant ◽

Early Stage Disease

8060 Background: ENKL is a rare and aggressive subtype of peripheral T-cell lymphoma. Due to its geographic predilection there is a paucity of data on clinical experiences from non-Asian countries. The purpose of this study was to analyze characteristics and outcomes of patients (pts) with ENKL identified from major academic centers in NA. Methods: Pts with newly diagnosed CD56+ ENKL were retrospectively identified. Analyses included disease characteristics, ethnicity, therapy, and outcomes. Results: 115 pts (63.5% Caucasian, 20% Asian, 16.5% other) were identified across 10 centers diagnosed between 5/1990-5/2011 (Era 1: pre-2000, n=16; Era 2: 2000-2005, n=45; Era 3: post-2005, n=54). Median age was 52 years (19-88). 75 (65%) had stage I/II disease and were treated with combined modality therapy (CMT) n=48, chemotherapy (CT) n=14 or radiotherapy (RT) n=14. 40 pts had stage III/IV disease and were treated with CT (n=23), CMT (n=12) or RT (n=5). CT regimens used alone or in CMT were either anthracycline-based (n=68) or other (n=29). 63% of stage I/II pts and 40% with stage III/IV achieved complete remission (CR). 30 pts underwent a stem cell transplant (SCT); 14 in first CR and 16 at progression/relapse (autologous, n=21; allogeneic, n=9). Pts with stage I/II disease had a better progression-free survival (PFS) and overall survival (OS) compared with stage III/IV (12 vs 5.2 months (p=0.003) and 41.5 vs 8.9 months (p<0.0001), respectively). For all stages, treatment with CMT compared with CT or RT alone was also associated with better PFS and OS, 18.0 vs 3.9 months (p<0.0001), and 41.5 vs 10.2 months (p=0.002) respectively. Non-anthracycline-based regimens were associated with better PFS (p=0.001) and OS (p=0.045). No survival differences were seen between Asian and non-Asian pts. Conclusions: This series represents one of the largest experiences of ENKL in NA. Our data are consistent with Asian studies in: 1) majority of pts present with early stage disease; 2) overall poor outcome; 3) superiority of CMT and non-anthracycline regimens. Advances in understanding biology and international collaborative efforts are required to improve outcome in this rare entity.

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Carboplatin-Paclitaxel Versus Cisplatin-Ifosfamide in the Treatment of Uterine Carcinosarcoma: A Retrospective Cohort Study

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000215 ◽

2014 ◽

Vol 24 (7) ◽

pp. 1256-1261 ◽

Cited By ~ 6

Author(s):

Domenica Lorusso ◽

Fabio Martinelli ◽

Maria Mancini ◽

Italo Sarno ◽

Antonino Ditto ◽

...

Keyword(s):

Overall Survival ◽

Area Under The Curve ◽

Progression Free Survival ◽

Oncologic Outcomes ◽

Uterine Carcinosarcoma ◽

Suitable Alternative ◽

Free Survival ◽

Gynecology And Obstetrics ◽

Group A ◽

Group B

ObjectiveUterine carcinosarcoma (CS) is a rare neoplasm whose adjuvant treatment has not been yet defined. We report on the activity and toxicity of cisplatin-ifosfamide and carboplatin-paclitaxel as adjuvant treatments for patients with uterine CS.MethodsData of International Federation of Gynecology and Obstetrics (FIGO) stage I to IV uterine CS patients treated between 2006 and 2012 with adjuvant chemotherapy (cisplatin 20 mg/mq and ifosfamide 1500 mg/mq day 1 to 4 every 3 weeks plus prophylactic Granulocyte colony-stimulating factor (G-CSF) support [group A] or carboplatin area under the curve -5 (AUC-5) and paclitaxel 175 mg/mq d1q21 [group B]) were retrospectively reviewed. Progression-free survival, overall survival, and chemotherapy-related toxicities were compared between the 2 groups. A subanalysis of oncologic outcomes according to the sarcomatous component (homologous vs heterologous) was performed.ResultsForty-six women were evaluated—21 in group A and 25 in group B. At a median follow-up of 30 months, the median progression-free survival was 11.6 months (95% confidence interval [CI], 6.3–16.9) and 16.6 months (95% CI, 14.7–18.5) for group A and B, respectively (P= 0.20). The median overall survival was 17.1 months (95% CI, 12.6–21.5) and 35.1 months (95% CI, 26.3–43.7) for group A and B, respectively (P= 0.14). No differences were identified among heterologous or homologous components according to chemotherapy treatment. Toxicity profiles widely differ between treatment arms.ConclusionsBecause of the super imposable activity and the better toxicity profile, carboplatin-paclitaxel may be a suitable alternative to cisplatin-ifosfamide in the treatment of uterine CS.

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Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39)

Journal of Clinical Oncology ◽

10.1200/jco.21.00306 ◽

2021 ◽

pp. JCO.21.00306

Author(s):

Kathleen N. Moore ◽

Michael Bookman ◽

Jalid Sehouli ◽

Austin Miller ◽

Charles Anderson ◽

...

Keyword(s):

Ovarian Cancer ◽

Progression Free Survival ◽

Figo Stage ◽

Phase Iii ◽

Stage Iii ◽

Newly Diagnosed ◽

Phase Iii Trial ◽

Free Survival ◽

Intention To Treat ◽

To Receive

PURPOSE To evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC). METHODS This multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100 ) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery. Patients were stratified by FIGO stage, Eastern Cooperative Oncology Group performance status, tumor immune cell PD-L1 staining, and treatment strategy and randomly assigned 1:1 to receive 3-weekly cycles of atezolizumab 1,200 mg or placebo (day 1, cycles 1-22), with paclitaxel plus carboplatin (day 1, cycles 1-6) plus bevacizumab 15 mg/kg (day 1, cycles 2-22), omitting perioperative bevacizumab in neoadjuvant patients. The co-primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat and PD-L1–positive populations. RESULTS Between March 8, 2017, and March 26, 2019, 1,301 patients were enrolled. The median progression-free survival was 19.5 versus 18.4 months with atezolizumab versus placebo, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.07; stratified log-rank P = .28), in the intention-to-treat population and 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI, 0.65 to 0.99; P = .038), in the PD-L1–positive population. The interim (immature) overall survival results showed no significant benefit from atezolizumab. The most common grade 3 or 4 adverse events were neutropenia (21% with atezolizumab v 21% with placebo), hypertension (18% v 20%, respectively), and anemia (12% v 12%). CONCLUSION Current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.

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Abiraterone versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer.

10.21203/rs.3.rs-269640/v1 ◽

2021 ◽

Author(s):

Takashi Ueda ◽

Takumi Shiraishi ◽

Saya Ueda ◽

Motoharu Ohashi ◽

Toru Matsugasumi ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Progression Free Survival ◽

Gonadotropin Releasing Hormone ◽

Free Survival ◽

Releasing Hormone ◽

Group A ◽

Psa Progression ◽

Hormone Sensitive ◽

Group B

Abstract ObjectivesTo compare the efficacy of abiraterone with that of bicalutamide in combination with gonadotropin-releasing hormone antagonist treatment for high risk metastatic hormone-sensitive prostate cancer patients.MethodsOne hundred and forty-nine patients with high risk metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and July 2020 were retrospectively identified. Fifty patients were administered abiraterone (1000mg/day) plus prednisolone (5mg/day) with gonadotropin-releasing hormone antagonist (degarelix) (group A) and 99 patients were administered bicalutamide (80mg/day) with gonadotropin-releasing hormone antagonist (group B). ResultsPSA- progression-free survival of group A was significantly longer than that of group B. Abiraterone therapy and Gleason score were significant independent factors for PSA-progression-free survival. By propensity score matching, total 56 matched patients were obtained. PSA-PFS (p<0.001) and OS (p=0.0071) of high risk mHNPC patients were significantly longer in abiraterone group of matched patients. Abiraterone therapy and Gleason score were still shown to be significant independent factors for PSA-PFS in matched patients.ConclusionsPSA-progression-free survival and overall survival in patients who were treated with abiraterone in combination with gonadotropin releasing hormone antagonist were significantly better than those of bicalutamide.

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A Long Survival of III-IVb Stage Nasopharyngeal Carcinoma Treated with IMRT with or without Nimotuzumab: a Propensity Score-matched Analysis

10.21203/rs.2.10899/v1 ◽

2019 ◽

Author(s):

Wang Zhi-Qiang ◽

Mei Qi ◽

Li Ji-Bin ◽

You Rui ◽

Liu You-Ping ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Propensity Score ◽

Intensity Modulated Radiotherapy ◽

Progression Free Survival ◽

Chinese Patients ◽

Term Survival ◽

Free Survival ◽

Distant Failure ◽

Group A ◽

Group B

Abstract Backgrounds: To assess the efficacy of Nimotuzumab in combination with first-line treatment of chemoradiotherapy of Chinese patients with primary III-IVb stage nasopharyngeal carcinoma. Methods: Patients with primary locoregionally advanced nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy (IMRT) and concurrent Cisplatin-based chemotherapy between January, 2008 and December, 2013 at a single institution were retrospectively reviewed. Group A received at least 6 doses of Nimotuzumab; Group B did not received Nimotuzumab. A propensity score matching method was used to match patients from each group in a 1:3 ratio. Results: In total, 730 eligible patients were propensity-matched, with 184 patients in Group A and 546 in Group B. There were no significant differences in patient and tumor characteristics between Group A and Group B. At a median follow-up of 74.78 months (range 3.53–117.83 months), locoregional recurrence, distant failure and death were observed in 10.68%, 11.10% and 16.03% of all patients, respectively. Estimated 5-year locoregional relapse–free survival, distant metastasis–free survival, progression-free survival and overall survival in the Group A versus Group B were: 85.34% versus 89.79% (P=0.156), 93.09% versus 85.61% (P = 0.012), 79.96% versus 77.99% (P = 0.117) and 88.91% versus 78.30% (P=0.006), respectively. Conclusions: This nimotuzumab-containing regimen resulted in a better long-term survival in III-IVb stage NPC patients, and warrants further prospective evaluation.

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Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation

Blood ◽

10.1182/blood-2011-02-338665 ◽

2011 ◽

Vol 118 (5) ◽

pp. 1231-1238 ◽

Cited By ~ 134

Author(s):

Gareth J. Morgan ◽

Faith E. Davies ◽

Walter M. Gregory ◽

Nigel H. Russell ◽

Sue E. Bell ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Response Rate ◽

Response Rate ◽

Autologous Transplantation ◽

Progression Free Survival ◽

Initial Therapy ◽

Newly Diagnosed ◽

Free Survival ◽

Overall Response ◽

Depth Of Response

Abstract As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n = 426) with melphalan and prednisolone (MP; n = 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P < .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P < .0001) and favorable interphase fluorescence in situ hybridization profile (P < .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111.

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