Top news of the week in cancer drug development and research.
USPSTF Releases Final Breast Cancer Screening Guideline
The USPSTF issued final guidelines that stand by its recommendation that women at average risk of breast cancer should not start routine screenings until they reach age 50 years and that they should then undergo testing every 2 years. Although screening mammography is effective in reducing deaths due to breast cancer among women aged 40 to 75 years, the USPSTF does not believe that the benefits sufficiently outweigh the risks for the broad screening programs.
Overall, the USPSTF guidelines apply to asymptomatic women who do not have preexisting breast cancer or a previously diagnosed high-risk lesion, or who are not at a higher risk level because of genetic mutations, a family history of the disease or a history of chest radiation at a young age. In those older than 75, the guideline indicates there is insufficient evidence. For the group aged 40 to 49 years, screening was given a C recommendation.
For the age 50 to 74 group, mammography every 2 years has a B recommendation. In creating the final version of the recommendations, the USPSTF conducted a review of the science since its 2009 recommendation. The draft recommendation was available for public comment from April 21 to May 18, 2015.
ASCO GU Highlights
Atezolizumab Highly Effective in Bladder Cancer
Second-line treatment with atezolizumab led to a median overall survival of 11.4 months in patients with locally advanced or metastatic urothelial carcinoma who had high PD-L1 levels, according to updated data from the pivotal phase II IMvigor 210 study. These updated findings suggest that atezolizumab has the potential to change the standard of care, according to lead investigator Jean H. Hoffman-Censits, MD.
Overall, regardless of PD-L1 status, 38 of 45 patients (84%) who responded to the anti­—­PD-L1 agent had ongoing responses. At a median follow-up of 11.7 months, ORR was 26% at at the IC1/2/3 level, 18% for the IC 1/2/3 subgroup, and 15% in all patients. Complete response rates were 11%, 6%, and 5%, respectively. Responses were also observed in several subgroups with poor prognostic factors, including visceral metastases, liver metastases, ECOG performance status of 1, and Hb <10 g/dL.
The median duration of response has not yet been reached. The median PFS was 2.1 months, regardless of PD-L1 status. Median OS was 11.4 months, 8.8 months, and 7.9 months, in the IC 2/3, IC 1/2/3, and overall populations, respectively, with 12-month OS rates of 48%, 39%, and 36%.
Nivolumab RCC Benefit Sustained Across Subgroups
Nivolumab’s second-line survival benefit in renal cell carcinoma was consistent across subgroups categorized by patient risk status, prior treatment, and degree of metastases. Median OS for patients with a favorable risk score by MSKCC criteria was not evaluable with nivolumab and 29.0 months with everolimus (HR, 0.80; 95% CI, 0.52-1.21).
For patients with a poor MSKCC risk status, median OS was 15.3 months versus 7.9 months, respectively (HR, 0.48; 95% CI, 0.32-0.70). In patients with bone metastases, median OS was 18.5 months with nivolumab versus 13.8 months with everolimus (HR, 0.72; 95% CI, 0.47-1.09). Median OS was 18.3 and 16.0 months, respectively, in patients with liver metastases (HR, 0.81; 95% CI, 0.55-1.18).
Among patients who previously received sunitinib, the median OS was 23.6 months with nivolumab versus 19.8 months with everolimus (HR, 0.81; 95% CI, 0.64-1.04). For patients with prior pazopanib, median OS was not evaluable versus 17.6 months, respectively (HR, 0.60; 95% CI, 0.42-0.84). Median OS in the overall study population was 25.0 months with nivolumab versus 19.6 months with everolimus (HR, 0.73; 98.5% CI, 0.57-0.93; P = .002). Based on earlier results from CheckMate-025, the FDA approved nivolumab in November 2015 for the treatment of metastatic RCC after the failure of an angiogenesis inhibitor.
Avelumab Shows Promising Activity in Refractory Urothelial Cancer
Avelumab demonstrated antitumor activity with an acceptable safety profile in a phase Ib trial of patients with metastatic urothelial cancer refractory to standard therapy. After a median follow-up of 3.5 months, 16 patients remained on treatment. There were seven responses (15.9%) by RECIST criteria, one of which was a complete response. The median duration of response was not reached, and six of the seven responses were ongoing at the time of data analysis.
The proportion of patients alive and free of progression at 12 weeks was 47.2%. Eight patients (18.2%) had tumor shrinkage of at least 30%, including in patients with visceral metastasis. In PD-L1-positive patients, the objective response rate was 40% (4/10) compared with 9.1% (2/22) in PD-L1-negative patients.
The median progression-free survival wasn’t reached for the PD-L1-positive patients versus 12 weeks in the negative group. The PFS at 12 weeks was 70% in the positive arm versus 45.5% for the PD-L1-negative.
Celecoxib/Zoledronic Acid Improves OS in Select Prostate Cancer Patients
Adding celecoxib and zoledronic acid to standard treatment extended survival in men with metastatic prostate cancer commencing first-line hormone therapy, according to updated data from the STAMPEDE trial. In the study, the addition of celecoxib alone to standard of care did not significantly improve failure-free survival (HR, 0.88; 95% CI, 0.75-1.04; P = .122) or overall survival (HR, 1.00; 95% CI, 0.82-1.22; P = .986).
The median OS was 68 months with a 5-year OS of 54% for both standard of care alone and with the addition of celecoxib. In the overall population, adding zoledronic acid to celecoxib and standard of care also did not significantly improve FFS or OS versus standard of care alone. Median FFS was 24 months in the combination arm versus 19 months in the control arm (HR, 0.85; 95% CI, 0.72-1.01; P = .058).
Median OS was 74 months versus 68 months, respectively (HR, 0.86; 95% CI, 0.70-1.06; P = .159). However, in a subgroup of patients with metastases at baseline, there was a significant improvement in both OS (HR, 0.78; 95% CI, 0.62-0.99; P = .040) and FFS (HR, 0.77; 95% CI, 0.63-0.93; P = .008) for the celecoxib/zoledronic acid arm compared with the control arm.