Novel systemic therapies for metastatic disease

2007 ◽  
pp. 173-189
Author(s):  
James Larkin
Keyword(s):  
Metastatic Disease ◽  
Systemic Therapies

Long-term survivorship in patients with metastatic renal cell cancer (mRCC) managed with metastasectomy: A retrospective study from the MD Anderson Cancer Center (MDACC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 504-504 ◽  
Author(s):  
Amishi Yogesh Shah ◽  
Matthew T. Campbell ◽  
Kirtan Das Nautiyal ◽  
Neda Hashemi ◽  
Surena F. Matin ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Metastatic Disease ◽  
Cell Cancer ◽  
Tumor Biology ◽  
Cancer Center ◽  
Md Anderson ◽  
Point Total ◽  
Long Term Survivors ◽  
Systemic Therapies

504 Background: Overall survival (OS) in mRCC has improved with targeted therapy; however, metastasectomy is still an important tool in select patients. This study evaluated outcomes of patients managed with metastasectomy ± systemic therapies. Methods: After IRB approval, we retrospectively reviewed records of mRCC patients who were treated at MDACC between 1/1/2001 and 12/31/2008 and report on those who survived >4 years with metastatic disease. OS was calculated from diagnosis of metastatic disease to death or last follow-up. Descriptive statistics were used. Results: 168 long-term survivors were identified; 101 patients were treated with metastasectomy at some point (total 205 resections). 42 patients had single metastasectomy; 59 had multiple resections (most common in lung and bone). 12 patients underwent serial metastasectomy alone (no systemic therapy), and 8 remain alive (range 4.6-12.9 years from met diagnosis). Conclusions: Patients with mRCC selected for metastasectomy had a significantly longer OS than those who received systemic therapies only. Whether this reflects tumor biology, therapeutic effect, or selection bias is unknown in this retrospective study. However, the prolonged survival in this group supports continued use of metastasectomy in carefully selected patients. [Table: see text] [Table: see text] [Table: see text]

Novel systemic therapies in hard to treat fibrolamellar hepatocellular carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16653-e16653
Author(s):  
Ariel Gliksberg ◽  
Claire O'Grady ◽  
Paul Kent
Keyword(s):  
High Risk ◽  
Metastatic Disease ◽  
Objective Response ◽  
Tumor Control ◽  
Primary Therapy ◽  
Early Results ◽  
Systemic Treatments ◽  
Multi Agent ◽  
Grade 3 ◽  
Systemic Therapies

e16653 Background: Fibrolamellar Carcinoma (FLC) is a very rare liver malignancy of young adults without underlying liver disease (0.02 per 100,000 in the US).. Complete resection is the primary therapy, but recurrence rates are still > 50%. Currently there are no established systemic treatments, especially for high-risk disease (unresectable, relapse, progression, or metastatic disease). At our institution triple therapy “TT” with Nivolumab/5FU/Interferon α-2b is our first line, followed by other novel combination therapies such as Gemcitabine/Oxaliplatin/Lenvantinib (GOL) or Nivolumb/Lenvantinib/Quecertin (NLQ). Objective: To evaluate the tolerability and early response of multi-agent systemic therapies in patients with high-risk FLC. Methods: Data from all patients with FLC who received systemic therapies from 5/2018 to 2/2020 was reviewed to assess tolerability, survival and toxicity. Results: Nineteen patients were treated with systemic therapies of which 16 (10F, 6M median age of 19) were evaluable based on follow up scans. Between our 16 patients they had relapsed 28 times, 12 had metastatic disease and 7 had tried 2+ systemic therapies. RECIST 1.1 objective response (CR+PR) and tumor control (CR+PR+SD) are 44% and 69%. Since starting multi-agent therapy, all 6 patients who had previously been treated with monotherapy, have already exceeded their previous longest time to progression. Thirteen patients were treated with “TT” [12.5 median cycles (6-38)]. Three patients were treated with NLQ including 2 who failed TT. Of these, the 1 evaluable patient achieved CR. Two patients were treated with GOL, 1 who failed TT and one who was post liver transplant, both had sustained PR of 6 and 9 months. Subsequently one died and one achieved CR. For the 6 patients who achieved remission before or during therapy, only 1 has relapsed. To date the period of response is already 68% longer than the previous best length of response. There was 1 withdrawal due to grade 3 colitis and 2 dose adjustments. All experienced mild adverse effects, most commonly fever, headache, and hypertension, with 3 patients with grade 3 toxicities. Conclusions: FLC is a devastating disease with patients often relapsing even after successful surgical remission. Currently there is a need for tolerable systemic therapies. Although at our institution, TT is our frontline therapy, there are other combinations of immunochemotherapies that we have used to treat FLC with preliminary success and minimal toxicities. Our early results show that multi-agent systemic therapy in hard-to-treat FLC is worthy of further study.

scholarly journals Clinical Insights Into the Biology and Treatment of Pancreatic Cancer

2016 ◽  
Vol 12 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Niharika B. Mettu ◽  
James L. Abbruzzese
Keyword(s):  
Pancreatic Cancer ◽  
Survival Rate ◽  
Metastatic Disease ◽  
Poor Prognosis ◽  
Management Strategies ◽  
Stage At Diagnosis ◽  
Localized Disease ◽  
The Relationship ◽  
Systemic Therapies

Pancreatic cancer is a devastating disease with a universally poor prognosis. In 2015, it is estimated that there will be 48,960 new cases of pancreatic cancer and that 40,560 people will die of the disease. The 5-year survival rate is 7.2% for all patients with pancreatic cancer; however, survival depends greatly on the stage at diagnosis. Unfortunately, 53% of patients already have metastatic disease at diagnosis, which corresponds to a 5-year survival rate of 2.4%. Even for the 9% of patients with localized disease confined to the pancreas, the 5-year survival is still modest at only 27.1%. These grim statistics highlight the need for ways to identify cohorts of individuals at highest risk, methods to screen those at highest risk to identify preinvasive pathologic precursors, and development of effective systemic therapies. Recent clinical and translational progress has emphasized the relationship with diabetes, the role of the stroma, and the interplay of each of these with inflammation in the pathobiology of pancreatic cancer. In this article, we will discuss these relationships and how they might translate into novel management strategies for the treatment of this disease.

scholarly journals Metastatic Uveal Melanoma—A Review of Current Therapies and Future Directions

2017 ◽  
Vol 13 (02) ◽  
pp. 100
Author(s):  
Emily N Kinsey ◽  
April KS Salama ◽  
◽  
Keyword(s):  
Survival Rate ◽  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Intracellular Signaling ◽  
Mapk Pathway ◽  
Poor Response ◽  
Standard Of Care ◽  
Mitogen Activated Protein Kinase ◽  
Future Directions ◽  
Systemic Therapies

The most common type of ocular melanoma is uveal melanoma, which includes melanomas that originate from the choroid, iris, or ciliary body. Although the survival rate for all cases of uveal melanoma is high, once metastatic disease occurs the survival rate drops dramatically. Currently no standard of care exists to guide management in metastatic uveal melanoma. The molecular biology in uveal melanoma is distinct from cutaneous melanoma. In most cases of uveal melanoma, the mitogen activated protein kinase (MAPK) pathway is activated through mutations in either GNAQ or GNA11. In uveal melanoma the most common site of metastatic disease is the liver, and a number of hepatic-directed therapies are available including surgery, radiofrequency ablation, and embolization. Conventional systemic chemotherapy has shown poor response rates in uveal melanoma. An increased understanding of the molecular genetics and intracellular signaling of uveal melanoma has led to the development of immunotherapy and targeted systemic therapies. This review will discuss the options for metastatic uveal melanoma including hepatic-directed therapies, systemic therapies, and future directions.

scholarly journals Unmet Medical Needs and Future Perspectives for Leiomyosarcoma Patients—A Position Paper from the National LeioMyoSarcoma Foundation (NLMSF) and Sarcoma Patients EuroNet (SPAEN)

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 886
Author(s):  
Bernd Kasper ◽  
Annie Achee ◽  
Kathrin Schuster ◽  
Roger Wilson ◽  
Gerard van Oortmerssen ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Basic Research ◽  
The United States ◽  
Position Paper ◽  
Joint Effort ◽  
Medical Needs ◽  
Systemic Treatments ◽  
Research Meeting ◽  
Unmet Medical Needs ◽  
Systemic Therapies

As leiomyosarcoma patients are challenged by the development of metastatic disease, effective systemic therapies are the cornerstone of outcome. However, the overall activity of the currently available conventional systemic treatments and the prognosis of patients with advanced or metastatic disease are still poor, making the treatment of this patient group challenging. Therefore, in a joint effort together with patient networks and organizations, namely Sarcoma Patients EuroNet (SPAEN), the international network of sarcoma patients organizations, and the National LeioMyoSarcoma Foundation (NLMSF) in the United States, we aim to summarize state-of-the-art treatments for leiomyosarcoma patients in order to identify knowledge gaps and current unmet needs, thereby guiding the community to design innovative clinical trials and basic research and close these research gaps. This position paper arose from a leiomyosarcoma research meeting in October 2020 hosted by the NLMSF and SPAEN.

Evolving natural history of metastatic prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5063-5063 ◽  
Author(s):  
Nellie Nafissi ◽  
Alan Haruo Bryce ◽  
Heidi E. Kosiorek ◽  
Richard Butterfield ◽  
Thai Huu Ho ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Natural History ◽  
Metastatic Disease ◽  
Survival Benefit ◽  
Metastatic Prostate Cancer ◽  
The Past ◽  
Systemic Treatments ◽  
Visceral Metastases ◽  
History Of ◽  
Systemic Therapies

5063 Background: The systemic therapies available to patients with metastatic prostate cancer (mPC) have improved dramatically over the past decade. Prior to 2010, the only agents with a proven survival benefit for patients with metastatic disease were androgen deprivation therapy and docetaxel. Since then, five new agents have been FDA approved and have proven survival benefit in phase III trials. Anecdotal experience suggests that the increased available lines of therapy have changed the profile of mPC to include a higher prevalence of visceral metastases. Methods: A retrospective review of 474 patients with prostate cancer who died in 2009 and in 2016 was performed. Patients with metastatic disease who had imaging within 6 months of death were included. A total of 164 patients were eligible for analysis. Results: Mean age at death overall was 77.4 years (SD 9.5) and did not differ signifiantly by cohort. Overall rates of visceral and distant metastases to include lung, liver, adrenal, brain, renal, spleen, and thyroid, were higher in patients who died in 2016 as compared to those who died in 2009 (40.0% and 26.1%, respectively, p = 0.07). Lung metastases were more prevalent in patients who died in 2016 versus in 2009 at 26.3% and 13.0%, respectively (p = 0.05). Patients who died in 2009 received a median of 3 (range 1-10) systemic treatments versus 4 (range 0-13) in those who died in 2016 (p = 0.005). Forty-four percent of patients who died in 2016 used five or more lines of systemic treatments compared to 26.1% of patients in 2009. Conclusions: The emergence of new systemic therapies for mPC is changing the natural history of the disease. Forty percent of patients now develop visceral metastases compared to 26% in the past. These changes will drive the need for new treatment approaches targeting visceral metastases. [Table: see text]

Outcome of patients with refractory malignant peripheral nerve sheath tumors (MPNST) enrolled on phase 2 trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e22534-e22534
Author(s):  
Srivandana Akshintala ◽  
Nicole C. Mallory ◽  
Yao Lu ◽  
Karla V. Ballman ◽  
AeRang Kim
Keyword(s):  
Metastatic Disease ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Peripheral Nerve Sheath Tumors ◽  
Choi Criteria ◽  
Significant Difference ◽  
Prior Surgery ◽  
The Impact ◽  
Systemic Therapies

e22534 Background: Multiple phase 2 trials using objective radiographic response rates (ORR) as end point have shown negative results in MPNST. Alternative endpoints such as progression free survival (PFS) may be more appropriate for identifying active agents. PFS from prior trials can provide a historical baseline for future single arm phase 2 trials in this rare disease. Methods: Outcomes of patients with recurrent or unresectable MPNST enrolled on one of five negative phase 2 trials (SARC001, 002, 009, 016, and 023) conducted by the Sarcoma Alliance for Research through Collaboration (SARC) from Nov 2001 – Mar 2016 were retrospectively analyzed to calculate PFS. PFS from SARC006, the phase 2 trial of upfront chemotherapy in newly diagnosed patients with unresectable or metastatic MPNST, was analyzed separately. The impact of neurofibromatosis type 1 (NF1) status, tumor location, metastatic involvement, and prior therapy on PFS was evaluated. Results: Sixty-four patients (29 male, median age 39 years (range 15-81)) with MPNST were enrolled on one of five trials of primarily single agent or combined targeted therapy that were determined to be inactive. Primary endpoint was ORR per RECIST, WHO, or Choi criteria. Patients had received a median of 1 (range 0-5) prior systemic therapies and majority had received prior surgery (77%) and radiation (61%), and had metastatic disease (73%) at enrollment. Median PFS was 1.77 months (95% CI 1.61-3.45), and PFS at 4 months was 16%. Greater number of prior systemic therapies was associated with worse PFS (univariate hazard ratio 1.31, 95% CI 1.03-1.68, p = 0.03). There was no significant difference in PFS based on treatment trial, response criteria, NF1 status, presence of metastatic disease, disease site at enrollment, and prior surgery or radiation. PFS at 4 months was 94% in 40 patients enrolled on SARC006 trial, none of whom had received prior systemic or radiation therapy. Conclusions: PFS in patients with recurrent/refractory MPNST enrolled on phase 2 trials is poor and the number of prior regimens may impact PFS. Our data provides a historical baseline PFS that can be used as a comparator in future single arm phase 2 trials in refractory and upfront MPNST patients.

Q&A: Apportionment of Musculoskeletal Impairment to Preexisting Metastatic Disease

2017 ◽  
Vol 22 (4) ◽  
pp. 14-15
Author(s):  
Christopher R. Brigham ◽  
James B. Talmage
Keyword(s):  
Metastatic Disease
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