Effects of baseline lactate dehydrogenase (LDH), interferon gamma (IFN-g) expression, and tumor mutational burden (TMB) on treatment response to first-line atezolizumab (A) + vemurafenib (V) and cobimetinib (C) in BRAFV600 mutation–positive advanced melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9523-9523
Author(s):  
Caroline Robert ◽  
Karl D. Lewis ◽  
Paolo Antonio Ascierto ◽  
Rodrigo Ramella Munhoz ◽  
Gabriella Liszkay ◽  
...  
Keyword(s):  
Group Performance ◽  
Performance Status ◽  
Recursive Partitioning ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Complete Response ◽  
Advanced Melanoma ◽  
First Line ◽  
L1 Data ◽  
Metastatic Sites

9523 Background: The phase 3 IMspire150 study showed that first-line A+V+C improved investigator-assessed PFS vs placebo (P)+V+C in BRAFV600E/K mutation–positive advanced melanoma (hazard ratio 0.78; P=.0249). Prior biomarker analyses showed that IFN-g or TMB > 10 mut/Mb were associated with greater PFS benefits with A+V+C (Lewis et al. J ImmunoTher Cancer 2020;8:A188-A189). We further evaluated the association of these biomarkers with outcomes. Methods: Exploratory recursive partitioning analysis (RPA) was used to model associations between PFS and age ( < 65 vs ≥65 y), Eastern Cooperative Oncology Group performance status (0 vs 1), liver metastases (yes vs no), metastatic sites (≤3 vs > 3), sum of longest tumor diameters ( < 44 mm vs ≥44 mm), baseline LDH (normal [n] vs elevated [e]), TMB ( < 10 vs ≥10 mut/Mb), PD-L1 (negative vs positive), and IFN-g (high [h; > Quartile 3; Q3] vs intermediate [ > Q1 and ≤Q3] vs low [≤Q1]). Time-to-event analyses were summarized using Kaplan-Meier estimates. Results: The RPA analysis included 208/256 (81.3%) patients (pts) from the A+V+C arm of IMspire150 for whom LDH, TMB, IFN-g, and PD-L1 data were available. RPA showed that LDH was associated with PFS. In pts treated with A+V+C and n-LDH, h-IFN-g signature was associated with longer PFS and higher rates of objective response (OR) and complete response (CR) vs low/intermediate (l/i) IFN-g (2-y PFS: 59% vs 38%; ORR: 77% vs 69%; CR: 38% vs 15%, respectively); TMB ≥10 mut/Mb was associated with more favorable outcomes in pts with e-LDH (Table). In contrast, neither IFN-g nor TMB discriminated PFS outcomes in n-LDH or e-LDH pt subgroups receiving P+V+C. Pts with e-LDH and TMB < 10 mut/Mb had poor PFS outcomes, with 2-y PFS rates of 9% and 3% and lower rates of OR (51% and 62%) and CR (5% and 9%) in the A+V+C and P+V+C arms, respectively. Similar trends were observed for duration of response (DOR), and for the subset of pts with BRAFV600E mutation–positive melanoma. A+V+C improved PFS vs P+V+C across all subgroups with the exception of e-LDH and TMB < 10. Conclusions: IFN-g and TMB discriminated PFS benefit in pts receiving A+V+C but not for those receiving P+V+C. Durable responses were observed for pts treated with A+V+C in the n-LDH + h-IFNg subgroups.[Table: see text]

Axitinib versus sorafenib as first‑line therapy in patients with metastatic renal cell carcinoma (mRCC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. LBA348-LBA348 ◽  
Author(s):  
Thomas E. Hutson ◽  
Jorge Gallardo ◽  
Vladmir Lesovoy ◽  
Salman Al-Shukri ◽  
Viktor Stus ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Survival Data ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

LBA348 Background: In the phase III AXIS trial, second-line therapy with axitinib resulted in significantly longer progression-free survival (PFS) versus sorafenib for mRCC. We conducted a multicenter, randomized, open-label, phase III trial to compare PFS of axitinib vs sorafenib as first-line therapy. Methods: Patients with untreated, measurable (RECIST v1.0), clear‑cell mRCC and Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomized 2:1 to axitinib 5 mg twice daily (BID) or sorafenib 400 mg BID. Randomization was stratified by PS. Primary endpoint was PFS per independent radiology committee. The study had 90% power to detect a 78% PFS improvement from 5.5 mo with sorafenib to 9.8 mo with axitinib, corresponding to a hazard ratio (HR) of 0.561 (overall 1-sided α=0.025). Results: Patients (N=288) were mainly from Eastern Europe (51%), Asia (25%), North America (14%), or South America (10%).Patient baseline characteristics for axitinib (n=192) vs sorafenib (n=96) included: median age, 58y vs 58y; male, 70% vs 77%; white, 71% vs 69%; favorable risk, 49% vs 55%; PS 0, 57% vs 57%; nephrectomy, 85% vs 90%. Median (m) PFS was 10.1 vs 6.5 mo with axitinib vs sorafenib (HR adjusted for PS, 0.767; 95% confidence interval [CI], 0.559–1.053; 1‑sided P=0.0377). In patients with PS 0 and 1, respectively, mPFS with axitinib vs sorafenib was 13.7 vs 6.6 mo (HR, 0.644; 95% CI, 0.419–0.991; 1‑sided P=0.022) and 6.5 vs 6.4 mo (HR, 0.931; 95% CI, 0.585–1.482; 1‑sided P=0.38). Objective response rates (ORRs) with axitinib vs sorafenib were 32.3% vs 14.6% (1‑sided P=0.0006 adjusted for PS). Overall survival data were not mature. All-grade all‑causality adverse events (≥20%) with axitinib vs sorafenib were diarrhea (50% vs 40%), hypertension (49% vs 29%), weight decreased (37% vs 24%), fatigue (33% vs 26%), decreased appetite (29% vs 19%), palmar-plantar erythrodysesthesia (26% vs 39%), dysphonia (23% vs 10%), asthenia (21% vs 16%), and hypothyroidism (21% vs 7%). Conclusions: The study did not achieve its primary endpoint statistically, but axitinib demonstrated numerically longer mPFS and significantly higher ORR vs sorafenib, with an acceptable safety profile, as first-line therapy for mRCC. Clinical trial information: NCT00920816.

A preliminary study of apatinib in Chinese patients with osteosarcoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e22500-e22500 ◽  
Author(s):  
Yong Zhou ◽  
Fan Tang ◽  
Li Min ◽  
Wenli Zhang ◽  
Rui Shi ◽  
...  
Keyword(s):  
Safety Profile ◽  
Kinase Inhibitor ◽  
Group Performance ◽  
Pulmonary Metastases ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Chinese Patients ◽  
First Line

e22500 Background: Osteosarcoma is the most common malignant tumor of bone that displays hyperproliferative characteristics and high vascularity, making vascular endothelial growth factor receptors (VEGFRs) become promising targets. Apatinib, a tyrosine kinase inhibitor targeting VEGFR-2, shows anti-cancer effects against a broad range of malignancies. This study reported the clinical experience of apatinib in osteosarcoma. Methods: We collected the medical data of osteosarcoma cases who received apatinib for at least one month in our hospital. The objective response rate (ORR), disease control rate (DCR), and 6-month progression-free survival (PFS) and overall survival (OS) rates were evaluated, and the safety profile was observed. The cut-off date of analysis was 01/17/2017. Results: Between May 2015 and Nov 2016, a total of 34 cases received apatinib with informed consent (4 as neoadjuvant, 1 as neoadjuvant and first line, 10 as first line, 15 as second line and 4 as third line). Among them, 18 (52.9%) cases suffered from pulmonary metastases before apatinib administration; 29 (85.3%) patients had an Eastern Cooperative Oncology Group performance status of 1–2. Initial dosages of 250, 425, and 500 mg/d were given to 5 (14.7%), 3 (8.8%), and 26 (76.5%) cases, respectively. Dosage adjustment occurred in only 8 (23.5%) patients. The median duration was 5.9 months (95%CI, 4.5–9.4 months). According to RECIST v1.1, complete response, partial response, stable disease and progressive disease were achieved in 1 (2.9%), 6 (17.6%), 25 (73.5%) and 2 (5.9%) patients, respectively. The ORR was 20.5%, and the DCR was 94.1%. Patients with pulmonary metastases showed a relatively better response to apatinib, as the ORR and DCR were 33.3% and 88.9%, respectively. As for safety analysis, the most 3 common adverse events (AEs) were hand-foot syndrome (HFS) (29, 85.3%), diarrhea (16, 47.1%), and decreased appetite (9, 26.5%). Nine grade III AEs were occurred including 3 HFS, 2 hypertension, 1 diarrhea, 1 oral mucositis, 1 proteinuria and 1 serious peeling. Conclusions: Apatinib seems to be effective in treating osteosarcoma with acceptable safety profile. Perspective clinical studies with adequate sample size are required to validate our results.

Multi-institutional phase 2 study of TLK286 (TELCYTA™, a glutathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer

2005 ◽  
Vol 15 (4) ◽  
pp. 593-600 ◽  
Author(s):  
J. J. Kavanagh ◽  
D. M. Gershenson ◽  
H. Choi ◽  
L. Lewis ◽  
K. Patel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Group Performance ◽  
Clinical Symptoms ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Active Agent ◽  
Complete Response ◽  
Ecog Ps

The purpose of this study was to determine the safety and efficacy of TLK286 (TELCYTA™), a glutathione analog prodrug, in patients with platinum and paclitaxel refractory or resistant ovarian carcinoma. Thirty-six patients with measurable disease were enrolled. TLK286 was administered at 1000 mg/m2 intravenously every 3 weeks. The endpoints were objective response rate assessed by Response Evaluation Criteria in Solid Tumors (RECIST) and survival. Adverse events were graded using the National Cancer Institute Common Toxicity Criteria. Thirty-four platinum refractory or resistant patients (94%) were evaluable for objective tumor response. Five patients (15%) had objective tumor responses, including one durable complete response (CR) of greater than 3 years and continuing. The disease stabilization rate was 50%, including one CR (3%), four partial responses (12%), and 12 durable disease stabilizations (35%). Responses were accompanied by improvement in clinical symptoms and Eastern Cooperative Oncology Group Performance Status (ECOG PS) and decline in CA125 levels. Median survival was 423 days with survival of 60% at 1 year and 40% at 18 months. TLK286 was well tolerated in this population. TLK286 is an active agent in chemotherapy-resistant ovarian cancer. Further studies of TLK286 in platinum and paclitaxel refractory or resistant ovarian cancer are in progress.

Anlotinib plus sintilimab in patients with recurrent advanced endometrial cancer: A prospective open-label, single-arm, phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5583-5583
Author(s):  
Wei Wei ◽  
Xiaohua Ban ◽  
Fan Yang ◽  
Yongwen Huang ◽  
Jibin Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Endometrial Cancer ◽  
Growth Factor ◽  
Systemic Chemotherapy ◽  
Kinase Inhibitor ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Growth Factor Receptor

5583 Background: Endometrial cancer is one of the most common gynecologic malignancies in the world. however, the effects of systemic chemotherapy are limited. The combination of targeted therapy with immunotherapy is a new research field in the treatment of malignant tumors. Anlotinib is a novel tyrosine kinase inhibitor with highly selective inhibition effects on multi-targets, especially on vascular endothelial growth factor receptor, Platelet-derived growth factor receptor and Fibroblast growth factor receptor. Sintilimab is a highly selective, fully humanized, monoclonal antibody, which blocks the interaction between Programmed death 1 and its ligands. This research aimed to evaluate the efficacy and safety of the combination of anotinib and sintilimab in patients with recurrent advanced endometrial cancer. Methods: Patients who received at least one platinum-based systemic chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1 were considered eligible for enrollment. Sintilimab was administered intravenously (200mg，q3w); anlotinib was taken orally (12mg qd, d1-14, 21 days per cycle). The treatment was continued until disease progression, death or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included duration of response, disease control rate (DCR), progression-free survival (PFS), overall survival and safety. Results: From November 2019 to to September 2020, 23 patients with a median age of 56 years (range: 37-70), FIGO stage IA (21.7%), IB (8.7%), II (4.4%), IIIA (13.1%)，IIIC (30.4%), IVB (21.7%) were enrolled. Among these participants, 22 patients were evaluable. The therapeutic evaluation showed the incidence of complete response, partial response, stable disease and progression disease was 13.6%, 63.7%, 13.6% and 9.1% respectively, yielding the ORR of 77.3% (95%CI: 58.3%-96.3%) and the DCR of 91.7% (95%CI: 79.8%-100%). ≥1 and ＜1 Combined Positive Score of PD-L1 expression were observed in 66.7% (14/21) and 33.3% (7/21) patients respectively, and the ORR was 92.9% (95%CI: 77.4%-100%) and 57.1% (95%CI: 18.4%-90.1%) in the two groups. The median time of the first response was 1.5 months (range, 0.7-12.8). The median PFS was not reached. Most of the occurring adverse events (AEs) were grade 1 or 2. Grade 3 AEs included ileus (4.3%), immune myocarditis (4.3%) immune peritonitis (4.3%), hand-foot syndrome (8.7%), neutropenia (4.3%), neutrophils decrease (4.3%), and hypertension (4.3%); Grade 4 AE was lymphocytosis (4.3%). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: Anlotinib plus sintilimab showed a promising antitumor activity with a favorable toxicity profile for patients with recurrent advanced endometrial cancer. We will report more data in the future. Clinical trial information: NCT04157491.

scholarly journals Axitinib plus avelumab in the treatment of recurrent glioblastoma: a stratified, open-label, single-center phase 2 clinical trial (GliAvAx)

2020 ◽  
Vol 8 (2) ◽  
pp. e001146
Author(s):  
Gil Awada ◽  
Laila Ben Salama ◽  
Jennifer De Cremer ◽  
Julia Katharina Schwarze ◽  
Lydia Fischbuch ◽  
...  
Keyword(s):  
Adverse Events ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Synergistic Activity ◽  
Open Label ◽  
Corticosteroid Dose

BackgroundNo treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB.MethodsAdult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids. Patients with a daily dose of ≤8 mg of methylprednisolone (or equivalent) initiated treatment with axitinib (5 mg oral two times per day) plus avelumab (10 mg/kg intravenous every 2 weeks) (Cohort-1). Patients with a higher baseline corticosteroid dose initiated axitinib monotherapy; avelumab was added after 6 weeks of therapy if the corticosteroid dose could be tapered to ≤8 mg of methylprednisolone (Cohort-2). Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria, served as the primary endpoint.ResultsBetween June 2017 and August 2018, 54 patients (27 per cohort) were enrolled and initiated study treatment (median age: 55 years; 63% male; 91% Eastern Cooperative Oncology Group Performance Status 0–1). Seventeen (63%) patients treated in Cohort-2 received at least one dose of avelumab. The 6-m-PFS% was 22.2% (95% CI 6.5% to 37.9%) and 18.5% (95% CI 3.8% to 33.2%) in Cohort-1 and Cohort-2, respectively; median overall survival was 26.6 weeks (95% CI 20.8 to 32.4) in Cohort-1 and 18.0 weeks (95% CI 12.5 to 23.5) in Cohort-2. The best objective response rate was 33.3% and 22.2% in Cohort-1 and Cohort-2, respectively, with a median duration of response of 17.9 and 19.0 weeks. The most frequent treatment-related adverse events were dysphonia (67%), lymphopenia (50%), arterial hypertension and diarrhea (both 48%). There were no grade 5 adverse events.ConclusionThe combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB.

scholarly journals CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study

2019 ◽  
Vol 3 (12) ◽  
pp. 1815-1825 ◽  
Author(s):  
M. O’Dwyer ◽  
R. Henderson ◽  
S. D. Naicker ◽  
M. R. Cahill ◽  
P. Murphy ◽  
...  
Keyword(s):  
Partial Response ◽  
Group Performance ◽  
Residual Disease ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Staging System ◽  
Complete Response ◽  
Weekly Schedule ◽  
Intention To Treat ◽  
Good Partial Response

Abstract Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was &lt;10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10−5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810.

scholarly journals Population Pharmacokinetics/Pharmacodynamics of Dabrafenib Plus Trametinib in Patients with BRAF-Mutated Metastatic Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 931 ◽  
Author(s):  
David Balakirouchenane ◽  
Sarah Guégan ◽  
Chantal Csajka ◽  
Anne Jouinot ◽  
Valentine Heidelberger ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Systemic Exposure ◽  
Progression Free Survival ◽  
The Elderly ◽  
Cox Models ◽  
Plasma Ratio ◽  
Metastatic Sites

Patients treated with dabrafenib/trametinib (DAB/TRA) exhibit a large interindividual variability in clinical outcomes. The aims of this study were to characterize the pharmacokinetics of DAB, hydroxy-dabrafenib (OHD), and TRA in BRAF-mutated patients and to investigate the exposure–response relationship for toxicity and efficacy in metastatic melanoma (MM) patients. Univariate Fisher and Wilcoxon models including drug systemic exposure (area under the plasma concentration curve, AUC) were used to identify prognostic factors for the onset of dose-limiting toxicities (DLT), and Cox models for overall (OS) and progression-free survival (PFS). Seventy-three BRAF-mutated patients were included in pharmacokinetic (n = 424, NONMEM) and 52 in pharmacokinetic/pharmacodynamic analyses. Age and sex were identified as determinants of DAB and OHD clearances (p < 0.01). MM patients experiencing DLT were overexposed to DAB compared to patients without DLT (AUC: 9624 vs. 7485 ng∙h/mL, respectively, p < 0.01). Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2 and plasma ratio AUCOHD/AUCDAB ≥ 1 were independently associated with shorter OS (HR: 6.58 (1.29–33.56); p = 0.023 and 10.61 (2.34–48.15), p = 0.022, respectively). A number of metastatic sites ≥3 and cerebral metastases were associated with shorter PFS (HR = 3.25 (1.11–9.50); p = 0.032 and HR = 1.23 (1.35–10.39), p = 0.011; respectively). TRA plasma exposure was neither associated with toxicity nor efficacy. Our results suggest that early drug monitoring could be helpful to prevent the onset of DLT in MM patients, especially in fragile patients such as the elderly. Regarding efficacy, the clinical benefit to monitor plasma ratio AUCOHD/AUCDAB deserves more investigation in a larger cohort of MM patients.

EAGLE: A phase 3, randomized, open-label study of durvalumab (D) with or without tremelimumab (T) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6012-6012 ◽  
Author(s):  
Lisa F. Licitra ◽  
Robert I. Haddad ◽  
Caroline Even ◽  
Makoto Tahara ◽  
Mikhail Dvorkin ◽  
...  
Keyword(s):  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Standard Of Care ◽  
Open Label ◽  
Phase 3 ◽  
Risk Of Death ◽  
Grade 3

6012 Background: EAGLE is a phase 3 study evaluating efficacy of D (anti-PD-L1 mAb) monotherapy and D+T (anti-CTLA-4 mAb) vs standard of care (SOC) in pts with R/M HNSCC who progressed following platinum-based therapy (NCT02369874). Methods: Pts were randomized 1:1:1 to D 10 mg/kg IV every 2 weeks (Q2W), D+T (D 20 mg/kg IV Q4W + T 1 mg/kg IV Q4W for 4 doses, then D 10 mg/kg IV Q2W), or SOC (investigator’s choice: cetuximab, taxane, methotrexate, or fluoropyrimidine-based regimen). The primary endpoint was overall survival (OS) with dual primary objectives of D+T vs SOC and D vs SOC. Additional endpoints included objective response rate (ORR), duration of response (DoR), and adverse events (AEs). Results: 240 pts were randomized to D, 247 to D+T and 249 to SOC. An imbalance for Eastern Cooperative Oncology Group performance status (ECOG PS) was seen in favor of the SOC arm (D, PS 0 = 26%, PS 1 = 74%; D+T, PS 0 = 26%, PS 1 = 74%; SOC, PS 0 = 32%, PS 1 = 68%). The risk of death was not statistically significantly different for D compared with SOC (HR: 0.88; 95% CI: 0.72–1.08; P = 0.20) or D+T vs SOC (HR: 1.04; 95% CI: 0.85–1.26; P = 0.76). Efficacy data are provided in the table. Treatment-related AEs Grade ≥3 were reported in 10.1% of pts (regardless of causality Grade ≥3 AEs were 41.4%) in the D arm, 16.3% (51.2%) for D+T, and 24.2% (44.2%) for SOC. Following treatment, 2% of pts in D, 5% in D+T and 15% in SOC received immunotherapy. Conclusions: D and D+T did not demonstrate a statistically significant improvement in OS compared to standard chemotherapy in pts with R/M HNSCC. Median OS and ORR of D arm were similar to other studies with checkpoint inhibitors. The SOC arm outperformed what has been seen for SOC arms in previous studies; subsequent immunotherapy may have confounded the OS analyses. The safety profile for D and D + T in R/M HNSCC is consistent with previous trials. Clinical trial information: NCT02369874. [Table: see text]

Influence of tumor size and Eastern Cooperative Oncology Group performance status (ECOG PS) at baseline on patient (pt) outcomes in lenvatinib-treated radioiodine-refractory differentiated thyroid cancer (RR-DTC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6081-6081 ◽  
Author(s):  
Lori J. Wirth ◽  
Sophie Leboulleux ◽  
Naomi Kiyota ◽  
Makoto Tahara ◽  
Kei Muro ◽  
...  
Keyword(s):  
Tumor Size ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Disease Characteristics ◽  
Kaplan Meier ◽  
Ecog Ps ◽  
Post Hoc

6081 Background: In SELECT, lenvatinib significantly improved progression-free survival (PFS) of pts with RR-DTC versus placebo (18.3 v 3.6 months; hazard ratio [HR]: 0.21 [99% CI: 0.14, 0.31]; P<0.001). Here we examine the treatment of RR-DTC with lenvatinib in relation to tumor size (sum of all targeted lesions) and ECOG PS. Methods: In this post hoc analysis of SELECT with pts randomized to receive lenvatinib, Kaplan-Meier estimates of time to ECOG PS ≥2 were calculated for subgroups of pts according to baseline ECOG PS or tumor size. Objective response rate (ORR) and Kaplan-Meier estimates of overall survival (OS) and PFS according to ECOG PS (0 or 1) at baseline were calculated. Correlations between ECOG PS at baseline (0 or 1) and maximum tumor shrinkage were calculated using one-way analysis of variance. Results: Pts with ECOG PS 0 or 1 at baseline had similar demographic and disease characteristics. ORR was 78.5% and 51.0% for pts with ECOG PS 0 and 1 at baseline, respectively (odds ratio [95% CI]: 3.508 [2.018, 6.097]). Mean maximum percent decrease in tumor size was significantly greater in pts with baseline ECOG PS 0 (-46.13%) versus pts with ECOG PS 1 (-37.16%; P=0.0017). For pts with ECOG PS 1 at baseline, time to ECOG PS ≥2 was numerically shorter with tumor size >60 mm versus tumor size ≤60 mm (HR [95% CI]: 1.450 [0.708, 2.967]). Additional results are summarized in the table. Conclusions: Among pts with RR-DTC, PFS, OS, ORR, and time to ECOG ≥2 were generally better for patients with lower ECOG PS or smaller tumor size at baseline. These results may indicate that it is beneficial to start lenvatinib in pts with RR-DTC early, before ECOG PS worsens and tumor size increases. Clinical trial information: NCT01321554. [Table: see text]

Octreotide Alone or With Prednisone in Patients With Advanced Thymoma and Thymic Carcinoma: An Eastern Cooperative Oncology Group Phase II Trial

2004 ◽  
Vol 22 (2) ◽  
pp. 293-299 ◽  
Author(s):  
Patrick J. Loehrer ◽  
Wei Wang ◽  
David H. Johnson ◽  
David S. Ettinger
Keyword(s):  
Thymic Carcinoma ◽  
Response Rate ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Survival Rates ◽  
Eastern Cooperative Oncology Group ◽  
Oncology Group ◽  
Octreotide Scan ◽  
To Receive

Purpose To determine the objective response rate, duration of remission and toxicity of octreotide alone or with the later addition of prednisone in patients with unresectable, advanced thymic malignancies in whom the pretreatment octreotide scan was positive. Patients and Methods Forty-two patients with advanced thymoma or thymic carcinoma were entered onto the trial, of whom 38 were fully assessable (one patient had inconclusive histology; three patients had negative octreotide scan). Patients received octreotide 0.5 mg subcutaneously tid. At 2 months, patients were evaluated. Responding patients continued to receive octreotide alone; patients with progressive disease were removed from the study. All others received prednisone 0.6 mg/kg orally qid for a maximum of 1 year. Results Two complete (5.3%) and 10 partial responses (25%) were observed (four partial responses with octreotide alone; the remainder with octreotide plus prednisone). None of the six patients without pure thymoma responded. The 1- and 2-year survival rates were 86.6% and 75.7%, respectively. Patients with an Eastern Cooperative Oncology Group performance status of 0 lived significantly longer than did those with a performance status of 1 (P = .031). Conclusion Octreotide alone has modest activity in patients with octreotide scan–positive thymoma. Prednisone improves the overall response rate but is associated with increased toxicity. Additional studies with the agent are warranted.

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