publication date: Jun. 8, 2018

Clinical Roundup

New treatment combination improves outcomes for some patients with colorectal cancer

Research from Roswell Park Comprehensive Cancer Center suggests a new treatment combination can extend survival for many patients with advanced colorectal cancer.

The study focused on the targeted drug nintedanib in combination with capecitabine, an approved standard therapy for colorectal cancer.

The phase I/II study was led by Patrick Boland, assistant professor of oncology in the department of medicine at Roswell Park. The research team sought to evaluate the recommended dose and efficacy of nintedanib, atyrosine kinase inhibitor, pluscapecitabine in patients with refractory metastatic colorectal cancer—those whose cancer progressed after they received standard chemotherapy.

The team, which includes researchers from City of Hope, reports that among 40 patients who received the new combination, progression-free survival at 4 months was 36%, compared to 25% in a historical comparison group receiving standard therapy alone—a statistically significant increase.

The authors conclude that this treatment combination was well tolerated and that its efficacy compares favorably to single-agent approaches.


Exact Sciences, Mayo Clinic identify blood-based DNA biomarkers to diagnose hepatocellular carcinoma

Researchers at Exact Sciences Corp. and Mayo Clinic announced progress toward developing a panel of novel, blood-based, DNA biomarkers that could accurately detect hepatocellular carcinoma, the most common cancer that originates in the liver.

The biomarker panel was shown to be 95 percent sensitive for detecting HCC across all stages. Sensitivity among patients with curable-stage disease was 91 percent. The panel has overall specificity of 93 percent, demonstrating its ability to discriminate between normal and diseased patients. Sensitivity and specificity are the most important statistical measures of a cancer detection test’s performance.

Individuals diagnosed with cirrhosis have the greatest risk of developing HCC, and it is recommended that they undergo ultrasound and blood monitoring every six to 12 months.

John Kisiel, the gastroenterologist and assistant professor of medicine at Mayo Clinic Medical School who led the study, said the current options for monitoring at-risk patients are “sub-optimal.”

“We estimate that fewer than half of at-risk patients are tested regularly, and some estimates suggest the monitoring rate is less than 20 percent in primary care settings, where most people get their care,” he said.

Using DNA extracted from the blood samples of 244 people, including 95 diagnosed across all stages of HCC, 51 with cirrhosis, and 98 healthy volunteers, researchers tested the samples against 15 biomarkers to identify the combination of six biomarkers that yielded the most accurate detection of HCC.

Exact Sciences and Mayo Clinic have been collaborators since 2009. The collaboration previously yielded Cologuard, the stool-based, advanced-DNA screening test for colorectal cancer.

The study results can be found here.


Opdivo demonstrates superior RFS vs. Yervoy for patients with resected stage III or IV melanoma

Bristol-Myers Squibb Co. announced updated results from the phase III CheckMate -238 trial evaluating Opdivo (nivolumab) versus Yervoy (ipilimumab) in patients with stage IIIB/C or stage IV melanoma who are at high risk of recurrence following complete surgical resection.

In updated results from the study, Opdivo continued to demonstrate statistically longer recurrence-free survival of 62.6%, the primary endpoint of the study, versus 50.2% for Yervoy (HR: 0.66, P<0.0001) at a minimum follow-up of 24 months across key subgroups, including disease stages and BRAF mutation status.

No new safety data were generated as part of the 24-month analysis. As previously reported from the 18-month analysis, Opdivo demonstrated a significantly lower rate of adverse events leading to discontinuation (9.7% of patients in the Opdivo arm compared to 42.6% of patients in the Yervoy arm) and treatment-related grade III/IV AEs (14.4% of patients in the Opdivo arm compared to 45.9% in the Yervoy arm).

In the study, Opdivo demonstrated superior RFS versus Yervoy, regardless of disease stage, PD-L1 expression or BRAF mutation status, with RFS rates of 62.6% with Opdivo compared to 50.2% with Yervoy in the intent-to-treat patient population.

In patients with stage IIIB melanoma, RFS rates at 24 months for Opdivo were 70.8% versus 60.7% with Yervoy; for patients with stage IIIC melanoma, RFS rates were 58.0% with Opdivo versus 45.4% with Yervoy; and for patients with stage IV melanoma, RFS rates for Opdivo were 58.0% versus 44.3% with Yervoy. In patients with BRAF mutant melanoma, RFS rates for Opdivo were 61.9% versus 51.7% with Yervoy; in patients with BRAF wild-type melanoma, Opdivo demonstrated a RFS of 63.5% versus 46.2% with Yervoy.

CheckMate -238 is an ongoing phase III, randomized double-blind study of Opdivo versus Yervoy in patients who have undergone complete resection of stage IIIB/C or stage IV melanoma. The trial randomized 906 patients 1:1 to receive either Opdivo 3 mg/kg every two weeks (n=453) or Yervoy 10 mg/kg (n=453) every three weeks for four doses and then every 12 weeks starting at week 24.

Patients were treated until disease recurrence, unacceptable toxicity or withdrawal of consent for up to one year. The primary endpoint is RFS, defined as the time between randomization and the date of first recurrence, new primary melanoma or death. After meeting the primary endpoint, the trial will continue to evaluate for overall survival, a secondary endpoint.


Opdivo plus Yervoy provide QOL improvements in RCC

Bristol-Myers Squibb Co. announced patient-reported outcomes data from the phase III CheckMate -214 trial in intermediate- and poor-risk patients with advanced renal cell carcinoma treated with the immuno-oncology combination Opdivo (nivolumab) plus low-dose (1mg/kg) Yervoy (ipilimumab) vs. sunitinib over a two-year follow-up period.

Patients in the study treated with Opdivo plus low-dose Yervoy reported significant benefits in disease-related symptoms and improvements to their cancer-related quality of life and well-being. These benefits occurred early during Opdivo plus low-dose (1mg/kg) Yervoy combination therapy and were largely maintained throughout the treatment period and through Opdivo maintenance therapy.

Relative to the current standard of care, patients in the Opdivo plus low-dose Yervoy arm reported fewer kidney cancer symptoms as measured by the NCCN Functional Assessment of Cancer Therapy-Kidney Symptom Index.
This benefit was significant at all but one post-baseline time point through two years of follow-up (P<0.05). Time to deterioration in FKSI-19 total score was also significantly delayed with Opdivo plus low-dose Yervoy versus sunitinib (HR 0.54; 95% CI, 0.46–0.63; P < 0.0001).

An additional analysis showed similar results with a significant benefit seen for Opdivo plus low-dose Yervoy relative to sunitinib on change from baseline at a pre-planned 25-week landmark. Assessed by FKSI-19 total score, with a mean difference of 3.55 (1.65 vs -1.9; P<0.0001), the analysis showed that patients in the Opdivo plus low-dose Yervoy arm experienced significantly better health-related quality of life scores in regard to disease-related symptoms, treatment side effects and functioning.

Additionally, longitudinal changes from baseline in health-related quality of life between treatment arms at 25 weeks, as assessed by the Functional Assessment of Cancer Therapy-General, also demonstrated a significant advantage for Opdivo plus low-dose Yervoy, with a mean difference of 3.71 (1.52 vs -2.19; P<0.0009) in the total score between arms.

Confirmatory results from FACT-G also showed significantly higher scores in the combination arm across a number of measures, including physical, functional and emotional well-being. Collectively, these data suggest a significant and consistent patient reported benefit of the combination relative to standard of care.

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