Highlighting Key Developments in Clinical and Strategic Thinking From Web-Based Sources


Newsworthy, Late-breaking Information from Web-based Sources, Professional Societies and Government Agencies

KEYNOTE-426: Pivotal Study Hits Two Benchmarks, Improvements in PFS, OS
A pivotal phase 3 trial investigating a combination of anti-PD-1 therapy Keytruda and Pfizer’s tyrosine kinase inhibitor Inlyta has shown a significant benefit on both overall (OS) and progression-free survival (PFS) in patients with kidney cancer.

The KEYNOTE-426 reportedly met both primary end­points in demonstrating statistically significant and clini­cally meaningful increases in OS and PFS in the first-line treatment of advanced or metastatic renal cell carcinoma (RCC), compared to sunitinib monotherapy.

The study also met the key secondary endpoint of objective response rate (ORR), with significant improve­ments for the Keytruda (pembrolizumab)/Inlyta (axitinib) combination compared with sunitinib. Results for OS, PFS and ORR were consistent regardless of PD-L1 expression and across all risk groups, while the safety profile of the combination “was generally consistent with that observed in previously reported studies for each therapy,” according to Merck.

$20 Million for Kidney Cancer Research
Congress appropriated $10 million to establish the Kidney Cancer Research Program (KCRP) in 2017. The appropria­tion was increased to $15 million for 2018, and $20 million for 2019. The amounts were included in the passage of a Defense Appropriations bill.

SEER-Based Study Tracks RCC Trends: Plateau in Incidence, Decline in Mortality
Despite an overall increase in the incidence of RCC over two decades, there has been a recent plateau in RCC incidence rates with a significant decrease in mortality. Investigation of incidence and mortality trends of RCC in the US using the cell Surveillance, Epidemiology, and End Results (SEER) database found some good news— a plateau of cases since 2008 and a drop in mortality since 2012. The 13 SEER registries were accessed for RCC cases diagnosed between 1992 and 2015

A total of 104,584 RCC cases were reviewed, with 47,561 deaths. The overall incidence was 11.281 per 100,000 person-years. Incidence increased by 2.421% per year (95% confidence interval, 2.096, 2.747; P < .001) but later became stable since 2008. However, the incidence of clear-cell subtype continued to increase (1.449%; 95% confidence interval, 0.216, 2.697; P = .024). RCC overall mortality rates have been declining since 2001. However, mortality associated with distant RCC only started to decrease in 2012, with an annual percentage change of 18.270% (95% confidence interval, −28.775, −6.215; P = .006).

Tivozanib, a TKI, Continues Its Comeback— at Least in Europe
Tivozanib (Fotivda) has been included in the upcoming European Society of Medical Oncology (ESMO) clinical practice guidelines for advanced renal cell carcinoma (aRCC), anticipated to be published at the end of this year. The outline of the new proposed guidelines was presented at the ESMO 2018 Congress in Munich and indicated that tivozanib will be included as a first-line treatment recom­mendation for aRCC clear cell histology patients. The update will position tivozanib as a treatment standard for good (or favorable) risk patients with a Class IIa recommen­dation, and a treatment option for intermediate risk patients with a Class IIb recommendation.

Tivozanib was originally evaluated in the TIVO-1 phase 3 trial as a first-line therapy in RCC going head to head against sorafenib. Despite that, trial results appeared to meet the primary end point (improvement in median progression-free survival (PFS), approval has only been granted by the EMEA for use in the EU. In the US, the FDA failed to approve tivozanib given questions about the TIVO-1 trial that includes the study’s cross-over design and its failure to show a significant survival benefit. In a second attempt to gain tivozanib approval in the US, AVEO has undertaken a new phase 3 trial named TIVO-3. Like TIVO-1 the trial design is once again a head to head trial against sorafenib, but this time in third line (failed two prior thera­pies) instead of first-line patients (or those who haven’t been previously treated). The TIVO-3 trial is now fully enrolled and despite some delays is expected to read out soon.

NCCN Updates Clinical Practice Guidelines to Include New Recommendations for Cabozantinib Tablets
The National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines to include new recommendations for cabozantinib (CABOMETYX tablets. With the updates, cabozantinib is recommended by the NCCN for the treatment of advanced RCC regardless of patient risk status (favorable-, intermediate-, and poor-risk).

Key highlights from the updated NCCN Clinical Prac­tice Guidelines for Kidney Cancer include:

  • Cabozantinib is the only preferred tyrosine kinase in­hibitor (TKI) treatment option for first-line patients in the poor- and intermediate-risk groups (Category 2A).
  • Cabozantinib is a recommended first-line treatment op­tion for favorable-risk patients (Category 2B).
  • The agent is the only preferred TKI treatment option for previously treated patients (Category 1).

Cabozantinib is the only TKI indicated for the treatment of advanced kidney cancer with NCCN-preferred status for intermediate and poor-risk groups in the first-line setting and the only TKI with preferred status for patients who have progressed on prior therapy,” The NCCN Clinical Prac­tice Guidelines are the recognized standard for clinical policy in cancer care and are developed through review of evidence and recommendations from physicians and oncology researchers. The NCCN kidney cancer panel’s de­cision to include cabozantiib as a Category 2A preferred option for the treatment of patients with previously untreated advanced RCC with poor- or intermediate-risk disease was based on the results of the phase 2 CABOSUN trial.

Hospitals Specializing in Cancer Treatment Ranked in Report
Along with its 2018-19 Best Hospitals Honor Roll rank­ings, U.S. News & World Report released its rankings for the top hospitals across several specialties. For the 2018-19 rankings, U.S. News analyzed data from nearly 5,000 hospi­tals and survey responses from more than 30,000 physi­cians to rank the top hospitals across 16 specialties. Among the factors considered for the rankings were survival rates, patient safety, specialized staff and hospital reputation. An estimated 158 hospitals were ranked in at least one specialty. For cancer these hospitals were ranked in the top 10:

  1. MD Anderson Cancer Center (Houston)
  2. Memorial Sloan Kettering Cancer Center (New York City)
  3. Mayo Clinic (Rochester, Minn.)
  4. Dana-Farber/Brigham and Women’s Cancer Center (Boston)
  5. Cleveland Clinic
  6. The Johns Hopkins Hospital (Baltimore)
  7. Seattle Cancer Care Alliance at UW Medical Center
  8. Moffitt Cancer Center (Tampa, Fla.)
  9. UCSF Medical Center (San Francisco)
  10. Hospitals of the University of Pennsylvania-Penn Presbyterian (Philadelphia)

Kidney Cancer Worldwide Hot Spots? Eastern Europe Highest in Rates
Eastern European countries have the highest rates of kid­ney cancer, according to a study by the American Institute for Cancer Research and its Continuous Update Report. Rates in these countries were significantly higher than countries elsewhere, with the highest rate in Belarus with 16.8 per 100,000 population. Among 20 countries ranked, the US was 13th on the list with 10.9 cases per 100,000.

The list of rates:

1 Belarus 16.8
2 Latvia 15.2
3 Lithuania 14.8
4 Czech Republic 14.7
5 Estonia 14.6
6 Slovakia 13.4
7 France (metropolitan) 12.5
8 Hungary 12.4
9 Iceland 11.9
10 Croatia 11.7
11 Urugay 11.4
12 Ireland 11.3
13 US 10.9
14 Slovenia 10.5
15 Canada 10.2
16 Norway 10.2
17 UK 10.2
18 Russia 10.0
19 Australia 9.8
20 Belgium, Singapore 9.4


Artificial-Intelligence Smartphone App Significantly Reduced Severity of Cancer Patients’ Pain and Hospital Admissions
A study of 112 people with metastatic solid tumors found that the use of an artificial intelligence (AI)-based smart­phone app reduced both the severity of patients’ reported pain and hospital admissions. After an 8-week period, patients who used the AI-powered app to monitor and address pain experienced a 20% reduction in the severity of pain and had nearly 70% lower risk of pain-related hospi­tal admissions than patients not using the app. The findings were presented at the 2018 Palliative and Supportive Care in Oncology Symposium in San Diego.

“There is a significant shortage of palliative care providers, which will only worsen in the future as our popu­lation ages,” said lead study author Mihir M. Kamdar, MD, Associate Director of the Division of Palliative Care and an interventional pain physician at Massachusetts General Hospital, Boston, Massachusetts. “This is one of the reasons why technology solutions to help manage palliative care challenges, such as cancer pain, are so important.”

According to the researchers, this is one of the first mobile apps to utilize both patient-reported outcomes and AI clinical algorithms to significantly decrease pain and reduce overall inpatient hospitalizations in patients with cancer-related pain. The app, named ePAL, was designed and studied as part of a collaboration between Partners HealthCare Pivot Labs, the Massachusetts General Hospital Division of Palliative Care, and the Massachusetts General Hospital Cancer Center. Fifty-six patients in the study were assigned to use the ePAL app, while an equal number were assigned to usual care. Patients using ePAL received alerts on their smartphones with daily pain management tips and were prompted to submit their pain levels three days a week. The AI in ePAL was able to distinguish urgent from non- urgent pain and provide appropriate patient-facing educa­tion in real time. If cancer pain was severe or worsening, the app connected patients to their clinicians for care. KCJ