ESMO 2017: Day 2 Recap

IMG_3948The second day of ESMO included the oral genitourinary (GU) oncology session that focused on renal cell (kidney) and urothelial (bladder) carcinoma.

Several years ago, the SWITCH study evaluated the sequence of sunitinib and sorafenib showing similar overall progression free survival and overall survival regardless of the order by which each drug was utilized. At ESMO 2017, results of the SWITCH-II trial were presented. This study tested the sequence of pazopanib and sorafenib in patients with advanced RCC of any histology (i.e. clear cell or non-clear cell).  The study sought to enroll 544 patients, but stopped after 377 patients due to slow accrual. Only half of the patients remained on study and switched to their assigned drug after tumor growth on drug #1. Overall, while the study didn’t complete planned accrual, there was a trend for improved progression-free and overall survival for the pazopanib → sorafenib sequence.

Historically when most patients were treated with cytokines (IL-2 and interferon), two randomized trials by U.S. and European cooperative groups showed that in the setting of metastatic kidney disease, patients live longer by first removing the kidney mass and then treating with interferon rather than treating with interferon without removal of the kidney. Since the introduction of new therapies in late 2005 which have higher rates of tumor shrinkage and longer lifespans for patients, it is unknown if patients should still have their kidney tumor removed prior to drug therapy.

IMG_3954In the EORTC 30073 SURTIME trial, European investigators decided to try to assess whether tumors remained under control longer and patients lived longer if surgery was performed first or if patients initiated sunitinib for 3 cycles prior to cytoreductive nephrectomy. Because enrollment was slow, the study design was changed to assess the percent of patients that were free of tumor progression at 28 weeks. Ninety-nine patients were randomized to immediate versus delayed surgery, most with large kidney tumors and intermediate-risk cancer. Overall there was no difference in the percent with cancer progression at 28 weeks with either approach.  With the caveat of a small study, there were trends for longer survival and less surgical complications in those with delayed surgery. While the amended study is not able to prove that delayed surgery is the better approach, it gives comfort for those physicians/patients that the choice to initiate medical therapy and then re-evaluate for surgery is acceptable. We await the results of the larger CARMENA study that is testing surgery followed by drug versus drug alone (with no surgery) to see if removal of the primary kidney tumor is necessary.

Additionally, two early-phase studies of novel drug combinations of immunotherapy + targeted therapy were presented. In a phase I study led by the NCI, the safety of the combinations of cabozantinib/nivolumab and cabozantinib/nivolumab/ipilimumab were tested in patients with a number of different treatment-refractory tumor types, especially urothelial and other types of bladder cancers. Overall, both combinations were deemed to be safe and are moving forward in a phase III trial. However, many toxicities did occur and most patients needed to reduce the dose of at least one drug so these combinations should only be used in a clinical trial setting.

IMG_3958The phase II portion of a phase I/II study testing the combination of lenvatinib + pembrolizumab. The initial (phase 1) portion of the study presented at ESMO 2016 determined the safe dose in patients with different types of tumors (mostly RCC). This year, new results were presented with 22 additional patients added to the 8 previously treated on the phase I portion. Overall, there was an impressive tumor response rate of 63%, with 83% significant tumor shrinkage in those patients treated in the 1st line setting. This combination is also being tested in a phase III study for patients with advanced RCC which will soon be opening at Weill Cornell Medicine and NewYork-Presbyterian.

Missed our Day 1 Recap of ESMO 2017? Check it out here.

Cancer Care During Extreme Weather: Precautions and Considerations

Blizzard on the road.With winter upon us, it is important for cancer patients to be prepared in the case of severe weather. During severe weather, such as a blizzard, it may be difficult to get to Weill Cornell Medicine. All of our physician practices have coverage 24 hours a day, 7 days a week, so if you have any urgent questions or concerns, please call the regular number and you will be able to reach the on-call physician.

If you are due for an infusion or injection during an episode of severe weather, we can discuss the risks/benefits of finding a safe way to get to the treatment center vs. delaying treatment vs. finding an alternative temporary treatment center.

Storms can cause travel delays, especially on roads, so consider allowing for extra time and taking public transportation whenever possible. Drive slowly, and remember that injuring yourself in an accident may also impact your cancer care. It may also be an option for you to stay in a hotel near the hospital to avoid hazardous road conditions.

NewYork-Presbyterian Hospital Weill Cornell Medical Center is open to serve patients 24 hours a day, 7 days a week. In the event that the outpatient center is closed or unavailable due a natural disaster (which is rare), the emergency department will likely be open.

If you are uncertain about travel conditions, the emergency hotline is 212-746-WCMC (9262). Travel alerts for road conditions are released by the Metropolitan Transit Authority (MTA). If you are having a medical emergency or need an ambulance, dial 212-472-2222 or 911.

For people undergoing cancer treatment, blizzards and cold winter weather can impact more than just the ability to travel to treatment. Patients are more susceptible to hypothermia since side effects of treatment can be dehydration, fatigue, and anemia. Patients undergoing or having previously received certain types of chemotherapy can experience extreme sensitivity to the cold. Other chemo patients can actually feel less sensitivity to the cold and a decreased sensation in the hands and feet. This may lead to a major problem because it puts you at risk for frostbite since you are unaware of how cold it really is. Also, patients with lower than normal amount of platelets in the blood, might result in more serious bruising or bleeding with an injury or fall.

It’s important that patients feel safe and prepared to “weather the storm” during severe weather, including a loss of power or blackout. When weather or other issues can be anticipated, make sure you have enough medication and food/supplies on hand.

In general, but especially after severe inclement weather, be sure to communicate with your physician and healthcare team if anything out of the ordinary happened. For example, close the communications loop if you ended up going somewhere else for treatment or ran out of medication. This way we can make sure we update your medical records.

Most importantly, trust your instincts and don’t panic in bad weather. Wishing everyone a very safe rest of winter!

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.
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