Tag: Cancer Treatment

Is Chemo The Best Bladder Cancer Treatment For All?

DR. SCOTT TAGAWA AND DR. BISHOY FALTAS

bladder_fb

The bladder is a muscular organ made up of several layers of cells. This image outlines the bladder, ureters and surrounding vessels.

State-of-the-art cancer care continues to evolve due to advances in all aspects of patient care – including diagnosis, and personalized treatment and management. By incorporating novel diagnostics, systemic therapies, molecular targeted therapies, immunotherapies, and other biotechnological strategies into treatment paradigms, patient outcomes continue to improve along the cancer continuum.

For patients with bladder cancer and other urothelial cancers (cancers of the bladder, renal pelvis and ureter), cisplatin-based chemotherapy remains the standard of care. This is based on decades of research through a series of randomized clinical trials showing that chemotherapy regimens containing cisplatin consistently lead to the best overall survival rates. Importantly, some patients with metastatic urothelial cancer who are treated with cisplatin-based regimens are cured.

However, cisplatin is hard on not just the cancer cells, but the body overall. As a result, not all patients are “fit” for cisplatin. There are standard criteria that are used to define patients for whom cisplatin is not a viable treatment option. These include kidney (renal) function as measured by a blood test and sometimes urine tests, performance status (a measure of how physically functional patients are), hearing loss, nerve damage (neuropathy/numbness), and heart failure. Some of the time, there may be trade-offs. For instance, some patients would trade off the risk of needing a hearing aid for a higher chance of tumor shrinkage (or even cure).

While it is well-known among physicians that not all bladder cancer patients are candidates for this treatment option, questions linger regarding what the best treatment option should be for these patients. To get to the bottom of this question, we reviewed the scientific evidence and Dr. Scott Tagawa recently presented our findings to a large group at the 34th annual Chemotherapy Foundation Symposium (CFS). This conference brought together over 2,000 cancer care clinicians across a multidisciplinary spectrum to provide updates on the most cutting-edge new agents, ongoing clinical trials and emerging developments in cancer treatment and diagnosis.

What did the science show?

According to recent data presented at the 2016 European Society of Medical Oncology (ESMO) meeting, the most common alternative treatment regimen for patients who are well enough to tolerate chemotherapy is the combination of carboplatin and gemcitabine chemotherapies. This was based on the review of data from 1426 patients with advanced urothelial carcinoma who were treated with chemotherapy.

Interestingly, there were some other global trends in the types of chemo prescribed. Centers that treated fewer patients with urothelial cancers were more likely to give alternative (non-cisplatin) chemotherapy to patients that did not meet any standard criteria for being unfit. The most common reason for being deemed unfit for cisplatin was the patient’s current level of kidney function. Unfortunately, data showed that patients who were fit for cisplatin, but received alternative chemotherapy lived much shorter than those who received cisplatin, and none of those patients in the study were alive at the 5-year mark.

One setting where cisplatin-based chemotherapy is very important is in the pre-operative setting where the goal is cure rather than just prolongation of life by months to years. Physicians should be aware of some “tricks of the trade” to optimize kidney function and other parameters to maximize the chance for cisplatin administration and cure. For patients, it’s important to consider at least getting a consultation at a center of excellence before making a treatment decision.

We also recently wrote an editorial in The Lancet outlining the value of immunotherapy for patients with advanced urothelial cancers who are unfit for cisplatin, and in particular checkpoint inhibitor immunotherapy. While not currently FDA-approved for this indication, a study using atezolizumab (Tecentriq) was published in this prestigious journal with a second supportive study utilizing pembrolizumab (Keytruda) presented at the ESMO meeting in October. Both studies used monoclonal antibodies that enable the immune system to become activated and fight cancer, and both demonstrated substantial responses in a subset of patients. Studies of the tumor and surrounding tissue testing for PDL1 expression are able to predict those with a higher likelihood of response, but even those with “negative” testing can respond. Tests of tumor genomics are also able to group tumors into those with a higher likelihood of response, but again, even those in the lower immune responding group can have a long-term response to immune treatment. Ongoing studies are needed to help predict response in a more powerful manner. One issue that we’ve recently examined is the difference in tumor genomics before and after chemotherapy highlighted by Dr. Faltas’ high-impact publication on the clonal evolution of urothelial cancer. Among other things, this highlights the importance of obtaining recent tissue from metastatic sites to gain the most accurate understanding of an individual patient’s tumor biology.

In summary, it is important for physicians to recognize when a patient may or may not safely receive certain chemotherapy regimens, such as cisplatin combinations in the case of urothelial carcinoma. In addition, research is ongoing for patients that are unfit for certain types of chemotherapy to prove whether or not immunotherapy should be used in patients who have not yet received chemotherapy. Several immunotherapy drugs are currently being tested in randomized clinical trials and these include patients that are unfit for cisplatin. Additionally, other drugs such as antibody-drug conjugates or monoclonal antibodies have shown promising activity in patients with advanced urothelial carcinoma, and these studies included patients unfit for cisplatin.

You’re Invited: Celebrate the End of Movember!

Each November, we are proud to participate in the Movember campaign by growing moustaches and raising money to increase awareness and support for men’s health issues. The Movember Foundation is committed to funding research that will halve the number of deaths from prostate and testicular cancer by 2030. At Weill Cornell Medicine, we too are committed to reducing cancer deaths and increasing cures, and we’ve been fortunate to receive many Movember research grants over the past several years.

We hope you can join us for a happy hour to raise money for this important cause and to celebrate the end of Movember! It’s also your last chance to see our ‘staches until next year.

Where?
Draught 55
245 East 55th Street
New York, NY 10022
When?
Thursday, December 1, 2016
6:30pm  – 8:30pm

Buy your tickets today for the early bird special– $35 includes 2 complimentary drinks, food, a chance to win an iPad mini, and more!

All ticket proceeds will be matched and benefit our Movember team, the Wild Weill Cornell Mos.

Special thanks to Bill Foxx and Onco360 for sponsoring the complimentary food and beverages. 

movember_hh-flyer

Learn more about our participation in Movember, why we’re so committed to the cause, and other ways you can get involved.

Immunotherapy and Prostate Cancer: What You Should Know

Cancer CureImmunotherapy, broadly defined as using the body’s own immune system to fight cancer, is one of the most exciting developments in cancer care. In oncology, for some patients using an immunotherapy treatment approach has resulted in some deep and prolonged responses.

The field of genitourinary (GU) oncology one was of the first sub-specialty areas to utilize immunotherapy and compared to many other tumor types, GU oncology has been using it for the longest amount of time — particularly for kidney (renal) and bladder cancers. There have been more recent advances across the board in immunotherapy, including the approval of atezolizumab by the FDA for bladder and urothelial cancers, marking the first new treatment for that tumor type in nearly three decades. Additionally, in select patients who have advanced urothelial cancer that has not responded to platinum-based chemotherapy, adding immunotherapy with pembrolizumab to the treatment regimen improved survival.

In the modern treatment era, prostate cancer was one of the first cancers to show a survival advantage with immunotherapy, specifically sipuleucel-T. Also known by the brand name Provenge, sipuleucel-T stimulates the immune system to seek out cancer cells and attack them. It represents the first therapeutic cancer vaccine in any cancer (treatment-focused as opposed to prevention-focused), and is FDA-approved for men with metastatic hormonal-resistant prostate cancer (mCRPC). Unfortunately, not all men respond to this treatment. At Weill Cornell Medicine and NewYork-Presbyterian, we are looking to improve responses to sipuleucel-T with our Newlink-sponsored study of sipuleucel-T followed by indoximod/placebo. In addition, since it is difficult to tell which patients are the best fit for this treatment and which ones are responding to sipuleucel-T, we continue collaborations with other researchers to work on developing blood tests to find biomarkers to help men in the future.

Additionally, recent data from the 2016 European Society of Medical Oncology (ESMO) annual meeting demonstrated promising results for using pembrolizumab (also called Keytruda) in metastatic hormonal resistant prostate cancer. This immunotherapy that works by inhibiting the PD-1 pathway and has been recently approved in other tumor types, such as melanoma and lung cancer. An initial study of the drug across different tumor types was highlighted at the ESMO meeting with significant responses in a proportion of men with prostate cancer whose cancers grew despite essentially all known therapies. In addition, a study influenced by and subsequently performed by different groups of WCM collaborators demonstrated that five men with progressive metastatic castration-resistant prostate cancer had major responses to this immune therapy, with PSA’s dropping by more than 99% and tumors greatly shrinking on scans. While all types of immunotherapy can lead to serious side effects, the treatment was generally very well-tolerated with minor side effects.

We are continuing the work to further define the subsets of men with advanced prostate cancer who can benefit from immunotherapy and we have a newly opened study of pembrolizumab for men with mCRPC. In this study, three groups of men will receive open-label (i.e. no placebo) pembrolizumab to test efficacy as measured by tumor shrinkage. We will also assess PSA changes and duration of tumor response, as well as biomarkers to help us determine in the future which men will receive the greatest benefit from this treatment.

Another promising immunotherapy-based prostate cancer treatment uses the monoclonal antibody (mAb) J591. J591 can recognize a protein antigen known as PSMA (also known as anti-prostate-specific membrane antigen) that is expressed on virtually all prostate cancer cells, and more heavily expressed in men with treatment-resistant metastatic forms of the disease. At the recent ESMO conference, we presented two clinical trials of J591 immunotherapy that are currently in progress here at Weill Cornell Medicine and NewYork-Presbyterian. One is for men with advanced prostate cancer and high (unfavorable) circulating tumor cell (CTC) count and the other delivers two doses of J591 prior to prostatectomy for men with intermediate and high risk prostate cancer. These trials are based upon the prior track record of this antibody in men with prostate cancer, including the fact that in initial pilot studies, men with advanced prostate cancer and a high number of CTCs had a decrease in tumor cell counts after J591. In addition, a prior study of J591 in combination with low-dose interkeukin-2 (IL-2) indicated that men with biochemically recurrent prostate cancer (rising PSA) did not develop metastatic disease as would have been expected without this intervention, and those with metastatic castration-resistant prostate cancer lived significantly longer than expected.

We also continue to utilize antibodies to deliver chemotherapy or radioactive particles to tumor cells with the intent of sparing normal cells. Three of these types of immunotherapy studies are currently enrolling for men with advanced prostate cancer, with others in development.

  • IMMU-132: This compound consists of a drug attached to an antibody which recognizes Trop2, a target that is over-expressed on prostate cancer cells. The antibody carries SN38, the active ingredient in irinotecan, which has shown prior responses in solid tumors. The drug has shown promising activity in breast and bladder cancer and is now being studied in prostate cancer.
  • Rovalpituzumab Tesirine “Rova-T” in Delta-Like Protein 3 (DLL3)-Expressing Advanced Solid Tumors: Our research has demonstrated that neuroendocrine prostate cancer (NEPC), one of the most aggressive and treatment-resistant prostate cancer subtypes, highly expresses DLL3. Rova-T uses an antibody to hone in on cells with DLL3 and take along a potent toxin to target those specific cells.
  • 177Lu-J591 + ketoconazole: In this clinical trial, J591 is radiolabeled with 177Lutetium, (177Lu) in order to deliver the drug directly to the prostate cancer cells. It is given in combination with an oral hormonal therapy drug which both attacks prostate cancer and at the same time, increases expression of PSMA, which is recognized by J591, leading to more targeting of the otherwise invisible tumor cells.