Current Therapeutics of Kidney Cancer: Landmark Trials

 

Chicago, IL (UroToday.com) Dr. Vaishampayan provided an excellent walk down memory lane, highlighting the landmark trials in kidney cancer over the last 20 years at this morning’s ASCO 2017 annual meeting session “Evolving Treatment Paradigm in Renal Cell Carcinoma.”

 

Dr. Vaishampayan started by highlighting SEER data that suggests that although the incidence of kidney cancer has increased over the past 40 years, the mortality rates have essentially stayed the same over this time period. IL-2 has been approved for treatment of advanced RCC since 1992 and results of 255 patients who received high-dose IL-2 therapy demonstrated an objective response rate (ORR) of 14%, complete response (CR) rate of 5%, partial response (PR) rate of 9% [1]. Data from the PROCLAIMSM trial of 352 patients receiving targeted therapy prior to or following high dose IL-2 demonstrated 4% CR, 13% PR, 39% stable disease (SD), and 43% progressive disease (PD) with IL-2, demonstrating a clinical benefit for patients who progressed on targeted therapy [2]. Conclusions from these IL-2 studies include the fact that certain patients treated with IL-2 will have a CR+PR (~15%), however the majority of these patients are intermediate and not high risk. Furthermore, despite the toxicities of IL-2, they are predictable and manageable, and it is a remarkably time and cost effective therapy. Dr. Vaishampayan then highlighted that based on a meta-analysis of phase III trials of cytoreductive nephrectomy in the interferon era, patients derive a statistically significant survival benefit [3]. However, as Dr. Vaishampayan notes, based on recent SEER data, only 1/3 of patients receive cytoreductive nephrectomy.

The early to mid-2000’s saw the development of TKI therapy. In 2007, Escudier et al. demonstrated that sorafenib compared to placebo prolonged progression-free survival (PFS) in patients with advanced RCC [4]. Additional trials that year also demonstrated improved PFS for sunitinib compared to interferon-alfa [5], as well as temsirolimus compared to interferon alfa, particularly in patients with poor prognosis [6]. In 2013, we saw the COMPARZ trial of pazopanib vs sunitinib in the 1st line for mRCC, demonstrating comparable efficacy between the two agents (median OS: sunitinib 29.3 months vs pazopanib 28.4 months), although with improved tolerability with pazopanib [7].

There is currently a plethora of phase III trials for second line therapy for patients with mRCC that have reported in the past few years. In 2015, the METEOR trial (cabozantinib vs everolimus) reported that PFS was longer in the cabozantinib arm compared to everolimus (HR for death 0.67, 95%CI 0.51-0.89) [8]. A recent updated analysis of this data demonstrated improved OS, delayed disease progression, and improved ORR for cabozantinib [9]. Finally, Motzer and colleagues assessed lenvatinib + everolimus and lenvatinib alone and found that PFS for patients treated with combination therapy (HR 0.40, 95%CI 0.24-0.68) and lenvatinib alone (HR 0.61, 95%CI 0.38-0.98) was improved compared to everolimus alone [10].

In conclusion, there are many novel immune therapy trials on-going, but the landmark trials have established efficacy of multiple therapies in advanced RCC. As Dr. Vaishampayan notes, with multiple therapies available, a discussion of risk/reward ratio should occur with each patient. Certainly, we have hopes that single biomarker driven therapy may eventually be possible, however this is not currently available to ultimately guide precise treatment management.

Presented By: Ulka N. Vaishampayan, Karmanos Cancer Institute, Detroit, MI, USA

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md

References:

1. Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995 Mar;13(3):688-696.
2. Clark JI, Wong MK, Kaufman HL, et al. Impact of sequencing targeted therapies with high-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients with Metastatic Renal Cell Carcinoma from an Ongoing Observational IL-2 Clinical Trial: PROCLAIMSM. Clin Genitourin Cancer 2017 Feb;15(1):31-41.
3. Flanigan RC, Mickisch G, Sylvester R, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol 2004 Mar;171(3):1071-1076.
4. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007 Jan 11;356(2):125-134.
5. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007 Jan 11;356(2):115-124.
6. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med2007 May 31;356(22):2271-2281.
7. Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 2013 Aug 22;369(8):722-731.
8. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015 Nov 5;373(19):1814-1825.
9. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in advanced renal cell carcinoma (METEOR): final results form a randomized, open-label, phase 3 trial. Lancet Oncol 2016 Jul;17(7):917-927.
10. Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomized, phase 2, open-label, multicenter trial. Lancet Oncol 2015 Nov;16(15):1473-1482.

at the 2017 ASCO Annual Meeting – June 2 – 6, 2017 – Chicago, Illinois, USA

From https://www.urotoday.com/conference-highlights/asco-2017/asco-2017-renal-cancer/96167-asco-2017-current-therapeutics-of-kidney-cancer-landmark-trials.html?utm_source=newsletter_4518&utm_medium=email&utm_campaign=asco-2017-day-2-highlights

9 Tips For Safe Travel With Diabetes

Many of these tips work for Cushing’s patients on Growth Hormone, as well.

 

Traveling, whether it be for business or pleasure can easily take you out of your diabetes care routine. Before hightailing it out of town, make sure you are prepared. A little extra homework will help keep your diabetes from putting any kinks in your long-awaited travel plans.

How you prepare greatly depends on where you’re going and for how long. Ask yourself, how will your lifestyle change while traveling? Will you be able to prepare your own food, or will you be eating out? Will you be able to maintain adequate exercise or will you have more down time?

These helpful tips can help you stay on track with your diabetes treatment plan during your summer vacation getaways.

Read more here: 9 Tips For Safe Travel With Diabetes | MedicAlert Foundation

To improve chronic pain, get more sleep (coffee helps too)

New research from Beth Israel Deaconess Medical Center (BIDMC) and Boston Children’s Hospital shows that chronic sleep loss increases pain sensitivity. It suggests that chronic pain sufferers can get relief by getting more sleep, or, short of that, taking medications to promote wakefulness such as caffeine. Both approaches performed better than standard analgesics in a rigorous study in mice, described in the May 8, 2017 issue of the journal Nature Medicine.

Source: To improve chronic pain, get more sleep (coffee helps too)

May is Melanoma Awareness Month

 

I’ve posted about our family’s experiences with melanoma before.  We were lucky and caught it in time but a good family friend didn’t.

May is designated as National Melanoma Month.   Included in that designation is National Melanoma Monday, which is the first Monday in May.  The American Academy of Dermatology has set aside this day to raise awareness about skin cancer.

Melanoma is a type of skin cancer, and it is the deadliest of skin cancers.

There will be many events focused on skin health, sun safety, tanning prevention, and skin cancer screenings and resources.

All are asked to join the American Academy of Dermatology in wearing orange and encouraging others to wear orange for skin cancer awareness.

Know the warning signs and check with your doctor if any of them appear.

Early signs of melanoma are changes to the shape or color of existing moles or, in the case of nodular melanoma, the appearance of a new lump anywhere on the skin. At later stages, the mole may itch, ulcerate or bleed. Early signs of melanoma are summarized by the mnemonic “ABCDE”:

  • Asymmetry
  • Borders (irregular with edges and corners)
  • Color (variegated)
  • Diameter (greater than 6 mm (0.24 in), about the size of a pencil eraser)
  • Evolving over time

These classifications do not, however, apply to the most dangerous form of melanoma, nodular melanoma, which has its own classifications:

  • Elevated above the skin surface
  • Firm to the touch
  • Growing

Metastatic melanoma may cause nonspecific paraneoplastic symptoms, including loss of appetite, nausea, vomiting and fatigue. Metastasis of early melanoma is possible, but relatively rare: less than a fifth of melanomas diagnosed early become metastatic. Brain metastases are particularly common in patients with metastatic melanoma. It can also spread to the liver, bones, abdomen or distant lymph nodes.

 

Kidney Cancer Symptoms: 12 Early Warning Signs of the Life-Threatening Disease

 

More than 12,000 people in the UK are diagnosed with kidney cancer each year, according to 2014 statistics.

And although 42% of cases are deemed “preventable”, only 50% of patients survive kidney disease for 10 or more years.  I will celebrate 11 years next month, on May 9!

It’s the seventh most common cancer in the UK and is much more prevalent in males.

But do you know the warning signs of the potentially deadly disease?

Here we reveal the 12 main symptoms of kidney cancer:

1. Blood in your pee  Not until the day I was diagnosed.

You may notice your pee is darker than normal or reddish in color. This could also be a sign of chronic kidney disease and bladder cancer.

2. A persistent pain in your lower back or side, just below your ribs No

3. A lump or swelling in your side (although kidney cancer is often too small to feel) No

4. Extreme tiredness (fatigue) Possibly, although I assumed it was from Cushing’s

5. Loss of appetite and weight loss No

6. Persistent high blood pressure Yes

7. A high temperature of 38C (100.4F) or above No

8. Night sweats No

9. In men, swelling of the veins in the testicles Nope

10. Swollen glands in your neck No

11. Bone pain No

12. Coughing up blood No

If you are concerned about any of these symptoms you should see you GP, they will carry out a series of tests, including urine and blood tests, in order to get an accurate diagnosis.

What are the treatment options?

The treatment will depend on the size and severity of the cancer and whether it has spread to other parts of the body.

These are the five main treatments:

1. Surgery to remove part or all of the affected kidney Yes, all plus some other stuff

This the main treatment for most people

2. Ablation therapies No

Where the cancerous cells are destroyed by freezing or heating them

3. Biological therapies No

Medications that help stop the cancer growing or spreading

4. Embolisation No

A procedure to cut off the blood supply to the cancer

5. Radiotherapy No

Where high-energy radiation is used to target cancer cells and relieve symptoms

For more information go to nhs.uk/Conditions/Cancer-of-the-kidney

Adapted from http://www.dailystar.co.uk/health/605586/Kidney-cancer-symptoms-treatment-males-females-early-warning-signs

Chronic Migraine Study

 

 

Chronic migraine headaches can interfere with work, family, and leisure.

Medications may not manage the pain, nausea, dizziness and other symptoms associated with migraines. This trial may help people suffering from chronic migraines maintain their lifestyle better – and it pays!

Learn more about this trial.