Management of salivary gland malignancies: current and developing therapies

2011 ◽  
Vol 2 (2) ◽  
pp. 86 ◽  
Author(s):  
Mark Agulnik ◽  
Camille F. McGann ◽  
Bharat B. Mittal ◽  
Sara C. Gordon ◽  
Joel B. Epstein
Keyword(s):  
Clinical Trials ◽  
Salivary Gland ◽  
Treatment Guidelines ◽  
Objective Response ◽  
Response Rates ◽  
Cytotoxic Agents ◽  
Disease Response ◽  
Phase Ii Studies ◽  
Duration Of Response ◽  
New Treatment

Salivary gland tumors are rare, clinically diverse neoplasms that represent less than 1% of all malignancies. In locoregional recurrent or metastatic disease, systemic therapy is the standard approach. While numerous small phase II studies have evaluated the activity of cytotoxic agents, either alone or in combination, the response rates are generally modest with objective response rates ranging from 15%–50%. Duration of response is cited in the range of 6–9 months. Given this, further evaluation of novel therapies is mandatory in these diseases. With the emergence of molecular targeted therapy, these tumors become optimal candidates for trials of investigational drugs and established drugs for new indications. Of note, given the often indolent nature of disease, only patients with progressive disease should be enrolled and treated on these clinical trials. Study designs must incorporate stringent inclusion criteria to enable accurate reporting of disease response and stabilization. With dedication and co-operation, patients with these rare neoplasms can be accrued to clinical trials and the establishment of new treatment guidelines will be forthcoming.

scholarly journals Management of salivary gland malignancies: current and developing therapies

2011 ◽  
pp. 86-94
Author(s):  
Mark Agulnik ◽  
Camille F. McGann ◽  
Bharat B. Mittal ◽  
Sara C. Gordon ◽  
Joel B. Epstein
Keyword(s):  
Clinical Trials ◽  
Salivary Gland ◽  
Treatment Guidelines ◽  
Objective Response ◽  
Response Rates ◽  
Cytotoxic Agents ◽  
Disease Response ◽  
Phase Ii Studies ◽  
Duration Of Response ◽  
New Treatment

Salivary gland tumors are rare, clinically diverse neoplasms that represent less than 1% of all malignancies. In locoregional recurrent or metastatic disease, systemic therapy is the standard approach. While numerous small phase II studies have evaluated the activity of cytotoxic agents, either alone or in combination, the response rates are generally modest with objective response rates ranging from 15%–50%. Duration of response is cited in the range of 6–9 months. Given this, further evaluation of novel therapies is mandatory in these diseases. With the emergence of molecular targeted therapy, these tumors become optimal candidates for trials of investigational drugs and established drugs for new indications. Of note, given the often indolent nature of disease, only patients with progressive disease should be enrolled and treated on these clinical trials. Study designs must incorporate stringent inclusion criteria to enable accurate reporting of disease response and stabilization. With dedication and co-operation, patients with these rare neoplasms can be accrued to clinical trials and the establishment of new treatment guidelines will be forthcoming.

scholarly journals Centralised RECIST Assessment and Clinical Outcomes with Lenvatinib Monotherapy in Recurrent and Metastatic Adenoid Cystic Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4336
Author(s):  
Laura Feeney ◽  
Yatin Jain ◽  
Matthew Beasley ◽  
Oliver Donnelly ◽  
Anthony Kong ◽  
...  
Keyword(s):  
Decision Making ◽  
Adenoid Cystic Carcinoma ◽  
Clinical Outcomes ◽  
Clinical Decision Making ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Response Rates ◽  
Clinical Decision ◽  
Adenoid Cystic ◽  
Phase Ii Studies

Adenoid cystic carcinoma (ACC) is a rare cancer of secretory glands. Recurrent or metastatic (R/M) ACC is generally considered resistant to cytotoxic chemotherapy. Recent phase II studies have reported improved objective response rates (ORR) with the use of the multi-kinase inhibitor lenvatinib. We sought to evaluate real-world experience of R/M ACC patients treated with lenvatinib monotherapy within the UK National Health Service (NHS) to determine the response rates by Response Evaluation Criteria of Solid Tumour (RECIST) and clinical outcomes. Twenty-three R/M ACC patients from eleven cancer centres were included. All treatment assessments for clinical decision making related to drug therapy were undertaken at the local oncology centre. Central radiology review was performed by an independent clinical trial radiologist and blinded to the clinical decision making. In contrast to previously reported ORR of 12–15%, complete or partial response was not observed in any patients. Eleven patients (52.4%) had stable disease and 5 patients (23.8%) had progression of disease as the best overall response. The median time on treatment was 4 months and the median survival from discontinuation was 1 month. The median PFS and OS from treatment initiation were 4.5 months and 12 months respectively. Multicentre collaborative studies such as this are required to evaluate rare cancers with no recommended standard of care therapy and variable disease courses.

Doxorubicin, mitomycin-C, and 5-fluorouracil (DMF) in the treatment of metastatic hormonal refractory adenocarcinoma of the prostate, with a note on the staging of metastatic prostate cancer.

1983 ◽  
Vol 1 (6) ◽  
pp. 368-379 ◽  
Author(s):  
C J Logothetis ◽  
M L Samuels ◽  
A C von Eschenbach ◽  
A Trindade ◽  
S Ogden ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mitomycin C ◽  
Pulmonary Metastasis ◽  
Metastatic Prostate Cancer ◽  
Objective Response ◽  
Staging System ◽  
Response Rates ◽  
Disease Response ◽  
Skeletal Involvement ◽  
Adenocarcinoma Of The Prostate

Sixty-two patients with metastatic hormonal refractory adenocarcinoma of the prostate received a combination of doxorubicin, mitomycin-C, and 5-fluorouracil (DMF). Thirty (48%) of the patients achieved an objective response. Response criteria excluded disease "stabilization" as a manifestation of response. Four clinical prognostic categories were identified: osseous I (OI) had metastatic axial skeletal involvement (23 patients); osseous II (OII) had axial and extremity skeletaL involvement (18 patients); visceral I (VI) had pulmonary metastasis (9 patients); and visceral II (VII) had pulmonary metastasis and involvement of other viscera (12 patients). The 20 responding patients survived a median of 47.5 weeks, whereas the 32 nonresponding patients survived a median of 23.8 weeks (n = 0.002). Response rates were highest among patients with OI (52%) and VI (88%) disease; response rates were lower amont patients with OII (33%) and VII (33%) disease. Responding patients in each clinical category survived longer than nonresponding patients except for those patients with VII disease. The median duration of response for patients with OI disease was 11 months, for OII 9.5 months, for VI patients it was 6.5 months, and VII patients it was 5 months. DMF is an effective treatment of metastatic hormonal refractory prostate cancer, resulting in consistent objective responses. The staging system employed identifies four clinical categories of metastatic prostate cancer and allows for accurate comparison of diet and stratification of study populations.

Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): A pooled analysis of five clinical trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4134-4134 ◽  
Author(s):  
J. Berlin ◽  
E. Van Cutsem ◽  
M. Peeters ◽  
J. R. Hecht ◽  
R. Ruiz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Phase Ii Studies ◽  
Common Skin

4134 Background: Panitumumab, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFr), is approved for EGFr-expressing mCRC patients (pts) with disease progression (PD) on or following fluoropyrimidine (5FU)-, oxaliplatin (Ox)-, and irinotecan (Ir)-containing chemotherapy. Skin toxicities are common with panitumumab; we examined the association between severity of skin toxicity and panitumumab efficacy. Methods: Data from 5 clinical trials were pooled (4 phase II studies and 1 phase III study). Pts with mCRC had documented PD on or after 5FU, Ox, and/or Ir. Pts received panitumumab 6 mg/kg every two weeks (Q2W) or 2.5 mg/kg weekly (QW) until PD or intolerability. Tumors were assessed using modified WHO or RECIST criteria (blinded central review in 4/5 studies). Endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). PFS and OS were measured from enrollment. Only pts with =2 infusions (exposure over 2 wks for QW dosing or over 4 weeks for Q2W dosing) were analyzed to help correct for lead-time bias. Results: 612 of 640 pts were included in the analysis set (62% were male, 92% were white, and median age [range] was 61 [21, 88] years). The median (95% CI) duration of PFS was 8.4 weeks (8.0 to 11.3), the median (95% CI) survival was 6.9 months (6.2 to 7.9), and the ORR (95% CI) was 9.0% (6.8 to 11.5). The most common skin toxicities (any grade, grade 3/4) were erythema (54%, 4%) pruritus (53%, 2%), dermatitis acneiform (52%, 5%), and rash (39%, 2%). ORR, PFS, and OS appeared to favor pts with grade 2–4 skin toxicity vs pts with grade 0- 1 skin toxicity ( table ). Conclusion: In this large combined analysis, severity of skin rash was correlated with increased efficacy of panitumumab in terms of ORR, PFS, and OS. [Table: see text] No significant financial relationships to disclose.

Bevacizumab in combination with taxane versus non-taxane-containing regimens for advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC): A systematic review.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19094-e19094
Author(s):  
Madhusmita Behera ◽  
Rathi Narayana Pillai ◽  
Taofeek Kunle Owonikoko ◽  
Sungjin Kim ◽  
Zhengjia Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Performance Status ◽  
Random Effect ◽  
Random Effect Model ◽  
Cytotoxic Agents ◽  
Ecog Performance Status ◽  
Phase Ii Studies ◽  
Weighted Median ◽  
Weighted Values

e19094 Background: In pre-clinical studies, the efficacy of anti-angiogenic agents depends on the specific chemotherapy given in combination. This appears to result from abrogation of activated circulating endothelial progenitor cells by cytotoxic agents, with the most favorable results noted with the combination of anti-angiogenic therapy with taxanes. We conducted a systematic review of published clinical trials that evaluated the efficacy of bevacizumab in combination with taxane or non-taxane containing regimens for untreated, non-squamous NSCLC patients. Methods: An extensive search of published clinical trials was conducted from electronic databases (MEDLINE, EMBASE, Cochrane) and meeting proceedings using relevant search criteria. Single arm phase II studies or randomized trials reporting the efficacy of bevacizumab combined with taxane or non-taxane regimens were selected. A systematic analysis of extracted data was performed using Comprehensive Meta Analysis (Version 2.2.048) software under the random effect model. Clinical outcome in patients treated with taxane versus non-taxane regimen was compared using point estimates for weighted values of median overall survival (OS), progression free survival (PFS), and response rate (RR). Results: Twenty-five studies reported between 2005-2013 were eligible. A total of 4,279 patients (1663 and 2616 in the taxane and non-taxane groups respectively) were included. The most common chemotherapy agents used with bevacizumab among non-taxane regimens were gemcitabine (65%), vinorelbine (12%) and pemetrexed (11%). The weighted median age of the population was 59 years (Males-60%; Adenocarcinoma-82%; ECOG performance status 0/1(%)- 39/58). The weighted median OS was 15.1 vs. 13.7 months (p= 0.07); PFS was 7.4 vs. 7.1 months (p=0.27); RR was 39.6% vs. 37.7% (p=0.29) for taxane and non-taxane groups respectively. Conclusions: The combination of bevacizumab with taxane containing regimens is associated with a trend towards improved survival, but not RR and PFS, over non-taxane regimens for first-line therapy of advanced non-squamous NSCLC.

PIVOT-10: A phase II study of bempegaldesleukin (NKTR-214) in combination with nivolumab (NIVO) in cisplatin (cis) ineligible patients with previously untreated locally advanced or metastatic urothelial cancer (mUC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS589-TPS589
Author(s):  
Robert A. Huddart ◽  
Arlene O. Siefker-Radtke ◽  
Arjun Vasant Balar ◽  
Mehmet Asim Bilen ◽  
Thomas Powles ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Objective Response ◽  
Locally Advanced ◽  
Significant Proportion ◽  
Phase 2 ◽  
Metastatic Urothelial Cancer ◽  
Evaluable Population ◽  
Duration Of Response ◽  
New Treatment

TPS589 Background: Checkpoint inhibitors can achieve durable responses in cis-ineligible 1L mUC. However, use is restricted to patients whose tumors are PD-L1 high. Approximately 70% of cis-ineligible patients have tumors with low PD-L1 expression, leaving a significant proportion of 1L mUC patients in need of new treatment options. Bempegaldesleukin (BEMPEG; NKTR-214) is a CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 βγ receptor. NIVO is an anti-PD-1 antibody that is approved for treatment in several types of cancers, including 2L mUC after treatment with a platinum agent. Early BEMPEG plus NIVO data in 1L mUC (cis-eligible and -ineligible) patients found an objective response rate (ORR) of 48% (13/27) in the efficacy evaluable population (defined as having undergone at least one post-baseline scan) and a CR rate of 19%, prompting this further exploration of BEMPEG plus NIVO in a phase 2 study (Siefker-Radke, 2019). Methods: This Phase 2 multi-national trial evaluates BEMPEG plus NIVO in previously untreated patients with cis-ineligible mUC. Eligibility also requires tumor tissue be analyzed by central laboratory to document PD-L1 status. Approximately 205 patients will be enrolled. BEMPEG (0.006 mg/kg) and NIVO (360 mg) are given intravenously (IV) on Day 1 of each 3-week cycle. The primary endpoint is ORR assessed per RECIST 1.1 by blinded independent central review (BICR) in patients with low PD-L1 expression (defined as Combined Positive Score [CPS] < 10). Secondary endpoints include ORR and duration of response in all treated patients, safety, and tolerability. Tumor and blood samples will be collected for biomarker analyses. Enrollment is ongoing. Clinical trial information: NCT03785925.

scholarly journals Efficacy of PD-1/PD-L1 blockade monotherapy in clinical trials

2020 ◽  
Vol 12 ◽  
pp. 175883592093761 ◽  
Author(s):  
Bin Zhao ◽  
Hong Zhao ◽  
Jiaxin Zhao
Keyword(s):  
Clinical Trials ◽  
Conventional Therapy ◽  
Odds Ratio ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Rates ◽  
Clinical Phase ◽  
Risk Of Death ◽  
Cancer Types

Background: Inhibitors targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have unprecedented effects in cancer treatment. However, the objective response rates (ORRs), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 blockade monotherapy have not been systematically evaluated. Methods: We searched Embase, PubMed, and Cochrane database from inception to July 2019 for prospective clinical trials on single-agent PD-1/PD-L1 antibodies (avelumab, atezolizumab, durvalumab, cemiplimab, pembrolizumab, and nivolumab) with information regarding ORR, PFS, and OS. Results: Totally, 28,304 patients from 160 perspective trials were included. Overall, 4747 responses occurred in 22,165 patients treated with PD-1/PD-L1 monotherapy [ORR, 20.21%; 95% confidence interval (CI), 18.34–22.15%]. Compared with conventional therapy, PD-1/PD-L1 blockade immunotherapy was associated with more tumor responses (odds ratio, 1.98; 95% CI, 1.52–2.57) and better OS [hazard ratio (HR), 0.75; 95% CI, 0.67–0.83]. The ORRs varied significantly across cancer types and PD-L1 expression status. Line of treatment, clinical phase and drug target also impacted the response rates in some tumors. A total of 2313 of 9494 PD-L1 positive patients (ORR, 24.39%; 95% CI, 22.29–26.54%) and 456 of 4215 PD-L1 negative patients (ORR, 10.34%; 95% CI, 8.67–12.14%) achieved responses. For PD-L1 negative patients, the ORR (odds ratio, 0.92; 95% CI, 0.70–1.20) and PFS (HR, 1.15; 95% CI, 0.87–1.51) associated with immunotherapy and conventional treatment were similar. However, PD-1/PD-L1 blockade monotherapy decreased the risk of death in both PD-L1 positive (HR, 0.66; 95% CI, 0.60–0.72) and PD-L1 negative (HR, 0.86; 95% CI, 0.74–0.99) patients compared with conventional therapy. Conclusion: The efficacies associated with PD-1/PD-L1 monotherapy vary significantly across cancer types and PD-L1 expression. This comprehensive summary of clinical benefit from immunotherapy in cancer patients provides an important guide for clinicians.

scholarly journals Estimation of US patients with cancer who may respond to cytotoxic chemotherapy

2020 ◽  
Vol 6 (8) ◽  
pp. FSO600
Author(s):  
Edward B Maldonado ◽  
Scott Parsons ◽  
Emerson Y Chen ◽  
Alyson Haslam ◽  
Vinay Prasad
Keyword(s):  
Treatment Guidelines ◽  
Metastatic Cancer ◽  
Objective Response ◽  
Cytotoxic Chemotherapy ◽  
Cytotoxic Agents ◽  
Cancer Drug ◽  
Patients With Cancer ◽  
The Usa ◽  
Cancer Types ◽  
Cancer Network

Aims, patients & methods: In this retrospective review, we sought to estimate the proportion of patients in the USA with advanced or metastatic cancer who are eligible for and may respond to recommended first-line cytotoxic chemotherapy based on National Comprehensive Cancer Network treatment guidelines. Results: Among 609,640 patients, we estimate 479,823 (78.7%, 95% CI: 78.6–78.8%) may be eligible for cytotoxic chemotherapy while 189,159 out of 609,640 patients (31.0%, 95% CI: 30.9–31.1%) may have achieved treatment response. The average objective response rate from these regimens was 48.6% (range 9.2 to 90.6%). Conclusion: Given the large role of cytotoxic agents in cancer, drug development in this space may remain of interest in specific cancer types, and regulatory approval of novel oncology drugs may justify head-to-head comparisons against cytotoxic regimens.

A phase II trial of pembrolizumab and poly-ICLC in patients with metastatic mismatch repair-proficient colon cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15552-e15552
Author(s):  
Nabin Raj Karki ◽  
Kulsum Bano ◽  
Sadek Ramses ◽  
Asha Nayak
Keyword(s):  
Colon Cancer ◽  
Mismatch Repair ◽  
Objective Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Response Rates ◽  
Metastatic Colon Cancer ◽  
Open Label ◽  
Duration Of Response

e15552 Background: Single agent programmed cell death protein 1 (PD1) inhibitor is ineffective against mismatch repair proficient (MMRp) colon cancer with response rates in single digits. Polyinosinic-Polycytidylic (Poly-ICLC) is a synthetic double stranded ribonucleic acid that generates inflammatory response increasing epitope recognition, develops tumor reactive T cells and induces interferon production which increases PD-L1 expression. In this trial, we test the effectiveness of combination of poly-ICLC and pembrolizumab in MMRp metastatic colon cancer. Methods: In this open label, single arm, single institution, phase 2 study, we enrolled 12 MMRp metastatic colon cancer patients from 1/25/2019 to 2/10/2021. Eligible patients had histologically confirmed MMRp metastatic colon cancer, ECOG 1-2 and progression on at least 2 lines of therapy. Treatment (Tx) consisted of Pembrolizumab (200 mg q3 weeks) and poly-ICLC (2 mg twice weekly, 3 days apart) for 1 year of treatment. Tx continued until progression, discontinuation or withdrawal. The primary endpoint was objective response rate by RECIST 1.1. Secondary endpoints included duration of response, adverse event profiling, progression free survival (PFS) and overall survival (OS). Intention-to-treat analyses (ITT) included all patient receiving at least one dose of the study agent. Results: 12 patients with median age 68.5 years (range 54-75) and 33% (4/12) male had been enrolled till 2/10/2021. Objective response rate was 8.3% (1 patient had partial response). The duration of response was 196 days. Among these 12 patients, median PFS was 63.5 days and median OS was 196 days. Treatment related adverse events of any grade were reported in 12/12 (100%) patients with the most common toxicities being nausea, vomiting, anorexia, dehydration and dizziness. 3/12 (25%) had serious (grade ≥ 3) toxicities and one patient died after experiencing leukocytosis, dehydration and hyperbilirubinemia attributed to the trial drugs. Conclusions: Poly-ICLC was not effective in combination with pembrolizumab for MMRp metastatic colon cancer in 3rd line setting and it did not seem to improve response rates to immunotherapy. Novel strategies for stimulating immunogenicity of cold tumors are needed. Clinical trial information: NCT02834052.

Bevacizumab in patients with advanced platinum-resistant ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5006-5006 ◽  
Author(s):  
S. A. Cannistra ◽  
U. Matulonis ◽  
R. Penson ◽  
R. Wenham ◽  
D. Armstrong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Prior Chemotherapy ◽  
Multiple Tumor ◽  
Platinum Resistant ◽  
Phase Ii Studies ◽  
Duration Of Response

5006 Background: Bevacizumab (BV), a recombinant, humanized monoclonal antibody directed against vascular endothelial growth factor, has demonstrated clinical benefit in multiple tumor types. Activity in ovarian cancer (OC) has been reported in phase II studies in patients (pts) with recurrent disease. We now describe the activity/safety of BV in pts with platinum-resistant OC (PROC) that progressed after topotecan or liposomal doxorubicin (LD). Methods: Eligibility criteria for this multicenter, Phase II study included primary or secondary PROC that progressed within 3 months of topotecan or LD, 3 or fewer prior chemotherapy regimens, and a performance status (PS) 0 or 1. BV was dosed at 15 mg/kg q 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) as defined by RECIST. A two-stage design was utilized with H1 set at 15%. Secondary endpoints included progression-free survival (PFS), duration of response, overall survival (OS), and safety. Results: The study enrolled 44 of the intended 53 pts, closing early due to a higher than expected rate of gastrointestinal perforations (GIP). Baseline characteristics included median age 60 yrs (range 31–87); PS 0 in 26 pts, 1 in 18 pts; 2 prior chemotherapy regimens in 20 pts, 3 in 24 pts. Preliminary efficacy: ORR (CR+PR), 7/44 (16%). Median duration of response was 12 weeks, with 2 pts continuing on study >5 months. Serious adverse events (SAEs) were reported in 18/44 pts (41%). Selected SAEs included GIP 5 (11%; one occurred more than 30 days after coming off study while on paclitaxel and commercial Avastin®), bowel obstruction 5 (11%), arterial thromboembolic events 4 (9%), delayed wound healing 2 (5%), and one case each of pulmonary hypertension, hypertensive encephalopathy, and hypoxia. Conclusions: BV has single agent activity in women with PROC, but is associated with substantial toxicity in this population. Trials are ongoing in less heavily treated, newly diagnosed pts with OC to evaluate the efficacy and safety of BV in these disease settings. Identification of risk factors for BV-associated adverse events requires further study. [Table: see text]

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