Tag: Cancer Treatment

Prostate Cancer Treatment: Getting the Best Results by Targeting the Right Cells at the Right Time

Lutetium 177 (also known as Lu-177 or 177-Lu) is a very popular radioactive particle used to treat prostate cancer in Europe, as it has previously been shown to be effective against metastatic prostate cancer. For more than 10 years, Weill Cornell Medicine has been one of very few centers in the United States that is able to offer this as a targeted prostate cancer treatment.

Lutetium 177 is a radioactive material that has a short-range, which means that it can act in a targeted fashion against cancer cells with little “collateral” damage to nearby organs and tissues. It needs some help to get to these specific cancer cells though, so we combine it with the J591 monoclonal antibody that binds to a protein expressed on nearly all prostate cancer cells, PSMA. Together, this treatment compound is called 177Lu-J591.

Here’s an overview of how we use monoclonal antibodies to target cancer cells, in this case the target is the prostate cancer tumors:

The treatment approach is called radioimmunotherapy because we’re using a tiny tag of radioactive material that can kill prostate cancer cells (in this case 177Lu) and attaching it to a very specific immune-based courier (J591) to help it get inside these cells.

We already know that 177Lu-J591 can be very effective at eradicating metastatic prostate cancer cells throughout the body. In 2013, we published results from a phase II clinical trial showing that a large, single-dose of this radioimmunotherapy could be safely delivered to patients and that those patients receiving a larger dose had better response and overall survival. This is what’s called a “dose-response.”

While higher doses of 177Lu-J591 are more effective at eradicating the prostate cancer cells, higher doses also increase the likelihood of side effects, including drops in the white blood cell and platelet counts in the blood.

Building on the results of this trial and additional scientific evidence, we hypothesized that by splitting the radiation dose and giving half at the first visit and half two weeks later (a process termed “dose fractionation”) that we would be able to deliver a higher dose of the treatment while minimizing the risk of these side effects.

Scott Tagawa_ASCO2016
Dr. Tagawa presents the clinical trial results at ASCO 2016 in Chicago

Today at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Scott Tagawa presented final results utilizing this split-dosed approach.

The clinical trial showed that the most effective split-dose of 177Lu-J591 was 45 mCi/m2 given in two sessions, two weeks apart, a dose 28% higher than was achievable with a large single-dose. Nearly 90% of the patients in this group experienced a decline in PSA levels, resulting in an average overall survival of more than four years. In addition, the number of circulating tumor cells (also known as CTCs or prostate cancer cells floating in the blood) was decreased or controlled by treatment. In addition to this study, the lower effect of fractionated therapy on blood counts has allowed combination of this therapy with chemotherapy.

This research was supported by the Department of Defense, Prostate Cancer Foundation and the National Institutes of Health.

FDA Approves New Combination Therapy for Kidney Cancer

Kidneys_GU Blog_FBOn May 13, the Food and Drug Administration (FDA) approved a new oral combination therapy for patients with advanced renal cell carcinoma (RCC), the most common kidney cancer in adults.

This combination therapy involves taking capsules of lenvatinib and everolimus on a daily basis. Both drugs are signal transduction inhibitors that stop some of the signals within cells that make them grow and divide. Lenvatinib (brand name Lenvima) works by inhibiting vascular endothelial growth factor (VEGF) receptors, halting blood vessel formation (angiogenesis) and fibroblast growth factor (FGF) receptors. FGF receptors are thought to be responsible for the development of cancer progression (treatment-resistance) following other anti-VEGF therapies. Levantinib was first FDA-approved in 2015 to treat some forms of recurrent and metastatic thyroid cancer. Everolimus stops a particular protein called mTOR from working which helps stop cancer growth. Everolimus was the first mTOR inhibitor approved in 2009 for the treatment of patients with advanced RCC after failure of treatment with sunitinib or sorafenib.

This treatment regimen is only FDA-approved as a second-line treatment for those who have already undergone one prior anti-angiogenic therapy. Common anti-angiogenic therapies for metastatic kidney cancer include sunitinib and pazopanib. Rather than targeting the tumor cells directly, anti-angiogenic therapies aim to prevent the growth of blood vessels the tumors depend on for survival.

Dr. Ana Molina of the Weill Cornell Medicine Genitourinary Oncology team led the initial study that tested this combined treatment which demonstrated that the regimen was not only safe, but showed impressive enough anti-cancer activity to warrant a larger, multi-center, randomized trial.

In the randomized trial that ultimately led to FDA-approval, patients who received lenvatinib and everolimus had significant improvement in progression-free survival (PFS) of 14.6 months versus 5.5 months with only everolimus. The overall response rate was 43% with the combination, compared with 27% with Lenvatinib alone and 6% with everolimus. The median overall survival was 25.5 months for the combination arm, 19.1 months in the Lenvatinib monotherapy arm and 15.4 months in the everolimus arm. Side effects included diarrhea, fatigue, high blood pressure (hypertension), nausea and vomiting, weight loss and protein in the urine.

We continue to offer lenvatinib and everolimus as combination therapy and encourage you to ask about whether it would a good treatment course for you.

Immunotherapies for Advanced Bladder Cancers

Cancer MicroscopeImmunotherapy is a very encouraging approach for treating bladder cancers and other tumors arising from the renal pelvis and ureters. There are a number of different types of bladder cancer immunotherapies currently available:

1. Atezolizumab (brand name Tecentriq) is an FDA-approved immunotherapy for urothelial carcinoma, the most common form of bladder cancer. Atezolizumab is an immune checkpoint blockade or “checkpoint inhibitor.” It selectively binds to cancer cells based on the presence of PD-L1, a protein on the tumor surface.

PD-L1 is more strongly expressed on certain types of tumors, including urothelial cancers arising from the bladder, renal pelvis, and ureters. PD-L1 prevents the body’s immune system from being able to recognize the cancer and attack it. It had been more than two decades since the FDA approved a new bladder cancer treatment.

Atezolizumab is only approved for urothelial carcinoma that has grown or recurred after previous chemotherapy, and we offer this treatment at Weill Cornell Medicine. We are also currently testing another PD-L1 checkpoint inhibitor alone or in combination with another immune checkpoint antibody versus standard chemotherapy through an open phase III clinical trial.

2. Ramucirumab is a monoclonal antibody that binds to the Vascular Endothelial Growth Factor (VEGF) receptor-2. This is a receptor found predominantly on blood vessels. Angiogenesis is a process where vessels grow to feed tumors and blocking this pathway can be helpful at stopping the growth of these vessels, particularly in combination with chemotherapy. We previously completed a randomized phase III trial which demonstrated that patients who got docetaxel (Taxotere) chemotherapy plus ramicurimab had more than twice the tumor shrinkage and double the time until tumor growth compared to docetaxel chemo alone; This study was recently published in the Journal of Clinical Oncology. Based upon our results, we recently opened a phase III trial using this drug in combination with chemotherapy. People who have already received chemotherapy, and those who have received chemo followed by atezolizumab or other checkpoint inhibitors are eligible for this clinical trial.

3. IMMU-132 (also known as Sacituzumab Govitecan) is an antibody drug conjugate that leverages the capability of monoclonal antibodies to attach to specific targets on cancer cells. By attaching a drug to the monoclonal antibodies, treatments are able to “hitch a ride” into the cancer cells.

This treatment is a potential good treatment fit for adults with metastatic bladder cancers who have not responded to chemotherapy or who have relapsed after chemotherapy or PL-1/PD-L1 checkpoint inhibitor immune treatment.

Initial positive results in the phase I trial led to a phase II clinical trial that is currently open to enrollment. Learn more about how this drug works in the body and get more information about our open IMMU-132 clinical trial by checking out our recent blog post, “Doing Better on Behalf of Bladder Cancer Patients.”

4. REGN2810 is a monoclonal antibody – a type of protein that works by blocking the programmed death receptor 1 (PD-1), a cell receptor on immune cells that is involved in preventing the immune cells from destroying other cells. Through our open clinical trial, patients with bladder and other urothelial cancers who have received prior treatment with checkpoint inhibitors (such as atezolizumab) can get the combination of the REGN2810 drug with immune boosters.