Efficacy of single-agent pemetrexed in platinum refractory metastatic urothelial cancer (mUC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 322-322 ◽  
Author(s):  
David J. Benjamin ◽  
Richard M. Bambury ◽  
Joshua Chaim ◽  
Emily C. Zabor ◽  
Irina Ostrovnaya ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Cox Regression ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Ecog Performance Status ◽  
Metastatic Urothelial Cancer ◽  
Significant Difference ◽  
Platinum Refractory ◽  
Line Of Therapy

322 Background: No standard therapy exists for platinum refractory mUC. Single agent pemetrexed (Pmt) had objective response rates (ORR) of 8% and 28% in two phase II studies (enrolling 13 and 47 patients) and is commonly used in this setting. To address the difference in reported ORRs, we performed a retrospective analysis of Pmt use at MSKCC to evaluate objective response in a larger cohort of patients. A secondary aim was to explore whether neutrophil-lymphocyte ratio (NLR) added prognostic value beyond known factors (time from prior chemotherapy (TFPC), ECOG performance status (PS), liver metastases, and hemoglobin) in the UC salvage setting. Methods: Patients who received Pmt for platinum refractory mUC between 2008 and 2013 were identified. Baseline demographics, clinical characteristics, prior therapies, Pmt dose, and number of cycles were recorded. ORR was determined according to RECIST 1.1. Kaplan-Meier method and Cox regression were used to analyze associations with overall survival (OS). Results: 135 patients were identified with median age 66 (range 45-88), male 76%, ECOG 0 in 14% / 1 in 54% / ≥2 in 32%. Pmt was administered as 2nd-line chemotherapy in 56% / 3rd line in 30% / ≥4th line in 14%. ORR was 7% with median duration of response 10.2 months. There was no significant difference in ORR by line of therapy or PS. Median progression free survival was 2.4 months and median OS was 6.6 months. In this dataset, TFPC was not prognostic, while liver metastases, PS, and hemoglobin were prognostic. Higher NLR was significantly associated with worse OS independent of other known factors. Conclusions: In the largest reported series to date, Pmt had an ORR of 7% in metastatic UC regardless of line of therapy or ECOG performance status. This limited activity highlights the urgent need to develop novel therapeutic strategies. NLR was identified as an independent prognostic factor in this setting. [Table: see text]

Efficacy of anti-PD(L)1 therapy for patients (Pts) with advanced urothelial carcinoma (aUC) with primary resistance to platinum-based chemotherapy (PC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16515-e16515
Author(s):  
Tyler F. Stewart ◽  
Nikhil V. Kotha ◽  
Hannah Elizabeth Dzimitrowicz ◽  
Dimitrios Makrakis ◽  
Ali Raza Khaki ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Cox Regression ◽  
Single Agent ◽  
Objective Response ◽  
Locoregional Therapy ◽  
High Risk Population ◽  
Primary Resistance ◽  
Best Response ◽  
Platinum Based Chemotherapy ◽  
Line Of Therapy

e16515 Background: PC remains standard first-line (1L) therapy for aUC. Approximately 15% of pts exhibit primary resistance (P-R) to PC and ∼25% progress by 4 months. PD(L)1 inhibitors yield objective response rates (ORR) of ∼20% in pts with progression after PC; however, it is unclear if this benefit extends to pts with P-R to PC. We examined the efficacy of anti-PD(L)1 in pts with aUC who experienced P-R to 1L PC. Methods: We conducted a multi-institutional retrospective study of pts with aUC who experienced P-R to PC and were subsequently treated with single-agent anti-PD(L)1 therapy. Eligibility included pts with unresectable or metastatic disease diagnosed after January 1, 2017. P-R to PC was defined as radiographic progression by RECISTv1.1 within 12 weeks from initiation of PC. Pts who developed metastatic disease while receiving (neo)adjuvant PC were eligible. Clinicopathologic variables were collected. ORR to anti-PD(L)1 was the primary endpoint. Secondary endpoints included time to treatment failure (TTF, defined as time from start of anti-PD(L)1 therapy to next line of therapy, hospice or death) and overall survival (OS) were estimated using Kaplan-Meier method. Multivariate (MV) analysis using Cox regression evaluating factors associated with OS was performed. Results: Overall, 42 pts were included: 74% male, median age 65 (28-90); 79% ever smokers; 21% mixed histology; 31% received definitive locoregional therapy. Metastatic sites at diagnosis of aUC included: lymph node only (19%), liver (29%), bone (38%) and lung (33%). At diagnosis of aUC, ECOG PS was 0 in 26%, 1 in 52% and unknown in 21%. 1L PC included cisplatin (76%) and carboplatin (24%) based regimens. Anti-PD(L)1 was received either 2L (98%) or 3L (2%). Overall, ORR to anti-PD(L)1 was 17%: CR (2%), PR (14%), SD (14%), PD (57%) and unknown (12%). Of the 24 pts with PD as best response to anti-PD(L)1, only 9 (38%) received subsequent therapy. Overall, median TTF was 4.2 mo (95% CI 2.8-6.7 mo) and median OS was 7.4 mo (95% CI 4.2-11.1 mo). ORR in patients with a PDL1 combined positive score ≥ 10% (n=6) was 0%: 1 SD and 5 PD. MV analysis for OS from start of anti-PD(L)1 is shown (Table). Conclusions: P-R to PC portends a poor prognosis in pts with aUC. While a subset of patients may respond to anti-PD(L)1 therapy, the majority of pts do not derive benefit. Alternative agents, e.g. antibody drug conjugates and FGFR inhibitors, and combination-therapy should be investigated for this high risk population.[Table: see text]

Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial.

1998 ◽  
Vol 16 (12) ◽  
pp. 3720-3730 ◽  
Author(s):  
H Joensuu ◽  
K Holli ◽  
M Heikkinen ◽  
E Suonio ◽  
A R Aro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
World Health ◽  
Second Line ◽  
Significant Difference

PURPOSE We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS Patients in the single-agent arm (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2 three times per week (CEF) followed by M 8 mg/m2 plus vinblastine (V) 6 mg/m2 every 4 weeks. Exclusion criteria included age greater than 70 years, World Health Organization (WHO) performance status greater than 2, prior chemotherapy for metastatic disease, and presence of liver metastases in patients younger than 50. RESULTS An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity was less in the single-agent arm and quality-of-life (QOL) analysis favored the single-agent arm. No significant difference in time to progression or survival was found between the two arms. Similarly, no difference in survival was found when the patients who received both the planned first-and second-line treatments were compared or when survival was calculated from the beginning of the second-line therapy. CONCLUSION Patients treated with single-agent E followed by single-agent M had similar survival, but less treatment-related toxicity and better QOL as compared with those treated with CEF followed by MV.

Association of sex, age and ECOG performance status with cancer immunotherapy efficacy in randomized controlled trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6592-6592
Author(s):  
Fang Yang ◽  
Yucai Wang ◽  
Grzegorz S. Nowakowski ◽  
Michael Wang ◽  
Ashish V. Chintakuntlawar ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Meta Analysis ◽  
Performance Status ◽  
Controlled Trials ◽  
Ecog Performance Status ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Control Therapy ◽  
Line Of Therapy ◽  
Ecog Ps

6592 Background: Sex, age and ECOG performance status (PS) may affect immune response and the efficacy of cancer immunotherapy with immune checkpoint inhibitors (ICI). We did a meta-analysis to assess the potential sex, age and ECOG PS differences of immunotherapy efficacy in advanced cancer. Methods: PubMed was searched up to January 15, 2019 for randomized controlled trials (RCT) comparing overall survival (OS) in patients with advanced cancer treated with ICI immunotherapy vs control therapy (without ICI). For sex difference analysis, pooled hazard ratio (HR) of death for men and women was calculated separately, and the heterogeneity between the two estimates was assessed using an interaction test by pooling study-specific interaction HR. Age ( < 65 vs ≥65) and ECOG PS (0 vs ≥1) difference was analyzed similarly. Subgroup analysis by cancer type and line of therapy (frontline vs subsequent) was explored. All analyses were done in Comprehensive Meta Analysis (v2) with random effects models. Results: Thirty phase 2/3 RCTs involving 17,728 patients were included. An OS benefit of immunotherapy was found for both men (HR 0.75, 95% confidence interval [CI] 0.69-0.81, P < 0.01) and women (HR 0.79, 95% CI 0.69-0.90, P < 0.01); for both younger ( < 65; HR 0.75, 95% CI 0.68-0.83, P < 0.01) and older (≥65; HR 0.76, 95% CI 0.69-0.83, P < 0.01) patients; and for both ECOG PS 0 (HR 0.78, 95% CI 0.69-0.89, P < 0.01) and PS ≥1 (HR 0.77, 95% CI 0.71-0.84, P < 0.01) patients. No significant difference of relative benefit from immunotherapy over control therapy was found in patients with different sex ( P = 0.283), age ( P = 0.906) or ECOG PS ( P = 0.783). In melanoma RCTs, compared with women (HR 0.77, 95% CI 0.64-0.94, P < 0.01), men (HR 0.56, 95% CI 0.42-0.76, P < 0.01) had more OS benefit from immunotherapy ( P = 0.037). No significant difference was found in other subgroup analyses by cancer types or line of therapy. Conclusions: Overall we found no evidence of association of sex, age, or ECOG PS with cancer immunotherapy efficacy. However, in melanoma, men might benefit more from immunotherapy than women.

OCEANS: A randomized, double-blinded, placebo-controlled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC).

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA5007-LBA5007 ◽  
Author(s):  
C. Aghajanian ◽  
N. J. Finkler ◽  
T. Rutherford ◽  
D. A. Smith ◽  
J. Yi ◽  
...  
Keyword(s):  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Type I ◽  
Ecog Performance Status ◽  
Fallopian Tube Cancer ◽  
Phase Iii Trial ◽  
Platinum Sensitive

LBA5007 Background: BEV, a humanized anti-VEGF monoclonal antibody, has shown a progression-free survival (PFS) benefit in 2 frontline phase III trials in patients with EOC, PPC and FTC. The therapeutic impact of BEV in combination with carboplatin (C) and gemcitabine (G) followed by single agent BEV to disease progression (PD) was evaluated in this phase III trial in the platinum-sensitive recurrent setting. Methods: Patients had recurrent, platinum-sensitive EOC, PPC or FTC, 1 prior regimen, no prior BEV, ECOG performance status 0-1, measurable disease. Subjects were randomized to: Arm A: [IV C (AUC 4, Day (D) 1) + G (1,000 mg/m2 D1 and 8) + placebo (PL) D1] q21D x 6 cycles (c) → PL q21D until PD or unacceptable toxicity (tox) Arm B: [CG + BEV (15 mg/kg) D1] q21D x 6 c → BEV q21D until PD or tox primary endpoint was investigator assessed PFS (RECIST). Secondary endpoints included objective response (OR), overall survival (OS), duration of response and safety. The design provided 80% power to detect a 27% reduction in the hazard of progression or death in Arm B vs A, limiting the overall type I error of 5%. Results: OCEANS enrolled 484 patients (242 per arm) from 4/07 - 1/10, median follow up of 24 months. BEV plus CG followed by single agent BEV to PD significantly increased PFS compared to CG alone (HR=0.484, p<0.0001). OR increased by 21% (p<0.0001). OS data is immature with only 29% of patients having had an event. The safety profile was consistent with other BEV trials. Conclusions: Results show a statistically significant and clinically relevant benefit when bevacizumab is added to chemotherapy in patients with recurrent, platinum sensitive EOC, PPC, and FTC. This is the first phase III trial of an antiangiogenic to demonstrate a clinical benefit to these patients. [Table: see text]

Peritoneum metastasis (PM) as a prognostic factor in metastatic gastric cancer (MGC) treated with anti-PD-1/PD-L1 monotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3051-3051 ◽  
Author(s):  
Yukiya Narita ◽  
Keiji Sugiyama ◽  
Seiichiro Mitani ◽  
Kazunori Honda ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Cox Regression ◽  
Negative Impact ◽  
Performance Status ◽  
Univariate Analysis ◽  
Objective Response ◽  
Metastatic Gastric Cancer ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Cox Regression Analysis ◽  
Line Therapy

3051 Background: Anti-PD-1 monotherapy has proven effective for the patients (pts) with MGC. However, the identification of biomarkers for predicting clinical outcomes remain as critical needs. We aimed to identify baseline characteristics associated with time to treatment failure (TTF) or overall survival (OS) for anti-PD-1/PD-L1 monotherapy as second- or later-line therapy in MGC. Methods: Routine blood count parameters and clinical characteristics at baseline were retrospectively investigated in 31 pts with MGC in Aichi Cancer Center Hospital. Endpoints were TTF and OS following anti-PD-1/PD-L1 monotherapy. Kaplan-Meiyer and Cox regression analysis were applied for survival analyses. Results: Patient characteristics were as follows: median age (range), 68 (47–83); ECOG performance status (PS) 0/1, 21/10; PM +ve/-ve, 12/19; No. of metastatic sites 1–2/≥3, 18/13; No. of prior chemotherapy regimens 1–2/≥3, 11/20; and absolute eosinophil count (AEC) <150/≥150 /μl, 14/17. Objective response rate and disease control rate (RECIST ver. 1.1) were 26% vs. 0% (odds ratio [OR], 3.76; P = 0.12) and 79% vs. 50% (OR, 3.58; P = 0.12) in the PM -ve group (Cohort A) and the PM +ve group (Cohort B), respectively. On univariate analysis, the pts with poor PS, PM +ve, and high AEC were significantly poor TTF; and poor PS and PM +ve were significantly identified as prognostic factors of poor OS. On multivariate analysis, only PM +ve was independent negative impact not only for TTF but also for OS. Median TTF and OS were 5.4 vs. 1.3 months (M) (adjusted hazard ratio [HR], 4.29; 95%CI, 1.60–11.5; P < 0.01) and 28.2 vs. 7.5 M (adjusted HR, 3.68; 95%CI, 1.25–10.8; P = 0.02) in Cohort A and Cohort B. Six-months TTF probabilities of 42% vs. 0% ( P = 0.03) and one-year OS probabilities of 58% vs. 8% ( P< 0.01) were observed in Cohort A compared to in Cohort B. Conclusions: PM -ve in the pts treated with anti-PD-1/PD-L1 monotherapy was associated with better efficacy. In the pts with PM -ve, anti-PD-1/PD-L1 monotherapy could be adapted in first-line therapy. [Table: see text]

Renal cell carcinoma (RCC) primary tumor shrinkage on vascular endothelial growth factor (VEGF)-targeted therapy (TT): A pooled analysis.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 629-629
Author(s):  
Dominick Bosse ◽  
Xun Lin ◽  
Ronit Simantov ◽  
Aly-Khan A. Lalani ◽  
Ithaar Derweesh ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Primary Tumor ◽  
Cox Regression ◽  
Performance Status ◽  
Objective Response ◽  
Pooled Analysis ◽  
Interferon Α ◽  
Tumor Shrinkage ◽  
Primary Tumors ◽  
Poor Risk

629 Background: Cytoreductive nephrectomy (CRN) is an important treatment modality in patients (pts) with advanced RCC, however the role and timing in the context of VEGF-TT remains under investigation. The aim of this study is to determine the efficacy of VEGF-TT to induce primary tumor shrinkage in advanced RCC. Methods: We conducted a pooled analysis of 12 Pfizer-sponsored trials in pts with metastatic RCC treated with sunitinib, sorafenib, axitinib, bevacizumab, termsirolimus or interferon-α. Primary endpoint was the primary tumor objective response rate (ORR) by RECIST in pts who have not undergone prior nephrectomy. Kaplan-Meier method was used to estimate median overall survival (OS) of responders (PR or CR) v. non-responders. Cox regression adjusting for demographics, histology type, prior therapy, metastasis sites, IMDC risk factors and neutrophil-to-lymphocyte ratio was used to compare OS between pts with and without primary tumor ORR. Results: 565 (12%) out of 4736 pts included had their primary tumors intact, of which 360 (8%) received VEGF-TT. In pts with primary tumor intact, 87% had clear-cell RCC and IMDC risk group were 4% favourable, 33% intermediate, 39% poor, 24% unknown. 35% had bone metastasis and 32% had liver metastases. 65% had ECOG performance status ≥1. Compared to pts with prior nephrectomy, primary tumor intact pts were more likely to have bone or liver metastases or to be IMDC poor risk. Primary tumor ORR was 17% (95% exact CI, 14, 20) in all pts, 19% (95% exact CI, 16, 23) in first line treated pts and 23% (95% Exact CI, 19, 28) in pts treated with VEGF-TT (any line). Primary tumor ORR was 20% (95% exact CI, 15, 26) in IMDC intermediate risk pts and 9% (95% exact CI, 5 – 13) in the poor risk. No pts had PD as best response in their primary tumor at the time they stopped systemic therapy. Median OS was 33.98 months in pts with primary tumor ORR and 9.8 months in pts without ORR, adjusted HR 0.42 [95%CI, 0.28, 0.6; p < 0.0001]. Conclusions: VEGF-TT resulted in primary tumor shrinkage in 23% of pts with IMDC intermediate and poor risk advanced RCC who have not undergone CRN. VEGF-TT may potentially facilitate future CRN in select pts. Trials assessing the utility of CRN are underway.

A randomized phase II study of axitinib in combination with pemetrexed/cisplatin (pem/cis) as first-line therapy for nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7551-7551 ◽  
Author(s):  
Chandra Prakash Belani ◽  
Nobuyuki Yamamoto ◽  
Igor Bondarenko ◽  
Sergey V Orlov ◽  
Jie Tang ◽  
...  
Keyword(s):  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
First Line Therapy ◽  
Randomized Phase Ii ◽  
Starting Dose ◽  
Grade 3 ◽  
To Receive

7551 Background: Axitinib is a potent and selective second-generation inhibitor of VEGF receptors 1, 2, and 3 that has promising single-agent activity in advanced NSCLC. Efficacy and safety of axitinib (in 2 dosing schedules) combined with pem/ciswere evaluatedfor non-squamous NSCLC. Methods: Patients with confirmed stage IIIB, IV, or recurrent non-squamous NSCLC and ECOG performance status (PS) 0 or 1 were stratified by gender and PS, and randomized 1:1:1 to receive six 21-day cycles of axitinib continuously plus pem/cis (arm I); axitinib on Days 2 through 19 followed by a 3-day interruption plus pem/cis (arm II); or pem/cis alone (arm III). Axitinib was administered at a starting dose of 5 mg BID. Pem/cis (500/75 mg/m2) was infused on Day 1 of each cycle. Primary endpoint was progression-free survival (PFS). Results: Baseline characteristics of patients in arm I (n=55), arm II (n=58), or arm III (n=57) ranged between 59–62 yr median age; 62–65% male; 71–85% White; 73–85% current/ex-smokers; and 43–47% PS 0. There were no significant differences in PFS or overall survival (OS) between axitinib-containing arms I and II compared with pem/cis alone, but objective response rates (ORR) were higher (Table). Most common all causality grade 3 adverse events (AEs) in arm I, II, and III, respectively, were hypertension (20%, 17%, 0%); neutropenia (18%, 10%, 9%); nausea (16%, 5%, 7%); vomiting (13%, 5%, 4%); fatigue (11%,16%,16%); and anemia (7%, 14%, 9%). Grade 4 AEs observed in >1 patient were asthenia and pulmonary embolism (2 patients each in arm II). Conclusions: Axitinib combined with pem/cis was generally well tolerated, but efficacy was not significantly better than pem/cis alone in non-squamous NSCLC. [Table: see text]

Heterogeneity of intermediate prognosis patients (pts) with metastatic renal cell cancer (mRCC) treated with sunitinib.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 446-446
Author(s):  
Avishay Sella ◽  
M. Dror Michaelson ◽  
Ewa M. Matczak ◽  
Ronit Simantov ◽  
Mariajose Lechuga ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kinase Inhibitors ◽  
Risk Model ◽  
Cox Regression ◽  
Performance Status ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Ecog Performance Status

446 Background: The Memorial Sloan Kettering Cancer Center risk model (MSKCC) stratifies pts with mRCC into 3 prognostic groups based on 5 risk factors. The Intermediate Prognosis (INTMP) risk group is characterized by the presence of 1 or 2 factors, equivalent to 15 possible distinct entities. This heterogeneity suggests that the efficacy of tyrosine kinase inhibitors may be less predictable in the INTMP than in the other groups. Methods: We identified 548 patients with INTMP mRCC from a pooled analysis of patients treated with sunitinib in 6 prospective phase II and III clinical trials. Statistical analysis was performed using Cox regression and Kaplan-Meier methods and Pearson chi-square tests. Results: Most INTMP pts were male (69%), with clear cell carcinoma (93%), good ECOG performance status (PS) (60.5% PS 0; 38% PS 1; 1.5% PS 2) and median age 60. There were 325 pts (56%) with 1risk factor, and the most common were <1 year from diagnosis (38%); low hemoglobin (Hg) (29%), or both (16%). Objective response rate (RR) was 35.4%, progression free survival (PFS) was 8.4 months (m) and overall survival (OS) was 20.5 m. The 325 (59.3%) pts with one risk factor fared better than the 223 (40.7%) patients with two: PFS 10.7 vs 6.5 m, HR 0.684(95% CI 0.563-0.832, p<0.001); OS 26.3 vs 14.1 m, HR 0.522 (95% CI 0.420-0.648, p<0.001). RR was similar (38.5% vs 30.9%, p=0.071). Sunitinib was more effective in pts with PS 0: PFS 9.7 vs 7.8 m, HR 0.797 (95% CI 0.654-0.972, p=0.0242); OS 24.7 vs 14.0 m, HR 0.529 (95% CI 0.426-0.657, p<0.001), RR 38.9% vs 30.1%, (p=0.036). The most common grade 3/4 adverse events (AE) were fatigue (17%), hypertension (10%), hand foot skin reaction (9%), and nausea (4%). Overall, 17% of patients discontinued due to AE, and the overall pattern of AEs did not vary among the subgroups. Conclusions: MSKCC INTMP is a heterogeneous group comprised mostly of pts with low Hg and/or < 1 year from diagnosis. PFS and OS are superior in pts with 1 vs. 2 risk factors, and PS is also an important factor in the INTMP group. Sunitinib is active and well-tolerated in INTMP pts. Clinical trial information: NCT00077974, NCT00083889, NCT00137423, NCT00267748, NCT00338884, NCT00054886.

SGN-30 (Anti-CD30 mAb) Has a Single-Agent Response Rate of 21% in Patients with Refractory or Recurrent Systemic Anaplastic Large Cell Lymphoma (ALCL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2718-2718 ◽  
Author(s):  
Andres Forero-Torres ◽  
STeven H. Bernstein ◽  
Ajay Gopal ◽  
Francine Foss ◽  
John P. Leonard ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Cell Transplant ◽  
Cutaneous Lesions ◽  
Ecog Performance Status ◽  
Good Tolerability ◽  
Poor Prognostic Factor

Abstract SGN-30 is a monoclonal antibody directed against the CD30 antigen expressed on some hematologic malignancies. Based on encouraging phase I data, a multicenter phase II study was conducted treating patients with refractory or recurrent CD30-positive ALCL with an ECOG performance status of ≤ 2. Thirty-nine patients (24M, 15F) with ALCL were enrolled, with a median age of 57 (range 23–82) and a median of 3 prior therapies (range 2–5). Nine patients had previously received a stem cell transplant. Eighty-five percent of tumors were negative for ALK, a poor prognostic factor. SGN-30 was administred at 6 mg/kg/wk (90 minute infusion, premedications were not required) for 6 consecutive weeks. After 24 patients were enrolled, the dose was escalated to 12 mg/kg/wk in subsequent patients. (Patients with stable disease or objective response were eligible to receive additional cycles of SGN-30. Five patients received ≥ 2 cycles of SGN-30.) Response assessments, as determined by CT scans, were performed 2 weeks after the last infusion. Best response is shown below: CR PR SD PD Pending Eval ORR *Both CRs have ongoing durations of >365 days; both patients received additional cycles of SGN-30. **PRs had durations of 27, 53, 139 and 167 days; two additional patients have ongoing durations of 86+ and 25+ days. ***Three SDs have ongoing durations of 96+, 365+, and 365+ days. Two additional patients had SD for 71 and 174 days. 2* 6** 5*** 24 2 21% Three drug-related toxicities ≥ Grade 3 were reported (each was considered possibly related to SGN-30): 1) lymphopenia, 2) catheter related infection and 3) urticaria. No other significant hematologic or biochemical toxicities have been observed. There was one definitely related serious adverse event (Grade 2) in a patient who experienced a transient exacerbation of his cutaneous lesions after 2 doses of SGN-30 but achieved a partial response after continuing on study. This phase II study represents one of the largest prospectively designed trials in relapsed/refractory ALCL and demonstrates good tolerability and clinically meaningful antitumor activity of SGN-30, especially in ALK negative patients who have a particularly poor prognosis.

Cetuximab (C) and bevacizumab (B) in patients with recurrent or metastatic head and neck squamous cell carcinoma: An updated report

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6049-6049 ◽  
Author(s):  
M. K. Gibson ◽  
M. Kies ◽  
S. Kim ◽  
P. Savvides ◽  
A. Kotsakis ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Growth Factor ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Bleeding Complications ◽  
Ecog Performance Status ◽  
Curative Intent ◽  
Biomarker Analysis

6049 Background: Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) represent important therapeutic targets in SCCHN. Cetuximab (C), an IgG1 monoclonal antibody against EGFR, has single agent activity in SCCHN. Upregulation of VEGF has been associated with C resistance, thus, combined targeting may enhance anti-tumor activity. We designed a phase II trial of bevacizumab (B), an anti-VEGF humanized monoclonal antibody, with C to evaluate this hypothesis. Methods: Eligible patients have recurrent or metastatic SCCHN, measurable disease (RESIST), ECOG performance status (PS) 0–2, and no history of bleeding or thrombosis. Up to 1 regimen (without an EGFR inhibitor) for recurrent or metastatic disease and prior chemoradiotherapy with curative intent are allowed. Treatment consists of weekly cetuximab, 250 mg/m2 (after a loading dose 400 mg/m2) and bevacizumab, 15 mg/kg given intravenously every 21 days, until disease progression. The primary endpoint is the objective response rate. Sample size is 45 eligible patients. Specific biomarkers relating to EGFR and VEGFR signaling will be evaluated in tumor tissues and blood samples. Results: 28 patients enrolled (27 eligible). Median age 60 years (range 33–92); male 19; PS 0 (7 pts), PS 1 (18), PS 2 (2). All had prior RT, and 26 had chemotherapy. A median of 4 cycles were given (range, 1–12). Best response in 25 evaluable patients: 5 (20%) PR (1 was uncomfirmed), 14 (56%) SD, and 6 (24%) PD. Progression-free survival was 2.8 months and median overall survival was 8.1 months. Grade (G) 3 adverse events included: hemorrhage (from a benign neck ulcer), 1; hypertension, 2; infection, 2; rash, 2; dysphagia, 4; hypophosphatemia, 1; and fatigue, 1. G 4 AEs: proteinuria, 1. One pt died of aspiration pneumonia, with possible cardiac ischemia of uncertain relationship to study drugs. Conclusions: Preliminary results show that cetuximab and bevacizumab is an active regimen in SCCHN with rare serious toxicities. In particular, our results establish the safety of this bevacizumab-based regimen in regards to bleeding complications in SCCHN. Study accrual continues and biomarker analysis is planned. (Supported by U01 CA099168–01 and P50 CA097190) No significant financial relationships to disclose.

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