Promising Treatments Emerging for mCRPC and RCC


FDA Approves FoundationOne Liquid CDx as Companion Diagnostic for Olaparib

The FDA has approved the FoundationOne Liquid CDx to be used as a companion diagnostic for olaparib (Lynparza), according to Foundation Medicine, the developer of the companion diagnostic.

The FoundationOne Liquid CDx uses a blood-based biopsy to identify BRCA1, BRCA2, and/or ATM alterations in patients with metastatic castration-resistant prostate cancer who may be appropriate for treatment with olaparib. The comprehensive genomic profiling test is now approved as a companion diagnostic for 7 targeted therapies across 4 tumor types.

The FoundationOne Liquid CDx is a qualitative next-generation sequencing–based in vitro diagnostic test, available only by prescription, that uses targeted high throughput hybridization-based capture technology to analyze 324 genes. It utilizes circulating cell-free DNA
isolated from plasma that is derived from anticoagulated peripheral whole blood of advanced cancer patients. Additional genomic findings may be reported by the test; however, these are not prescriptive or conclusive for labeled use of any specific therapeutic product.

Moreover, use of the test does not guarantee that a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Patients who are negative for companion diagnostic mutations should be reflexed to tumor tissue testing, and their mutation status should be confirmed using an FDA-approved tumor tissue test, if feasible.

The FoundationOne Liquid CDx was approved by the FDA in August to report genomic alteration results for patients with any solid tumor. Notably, Foundation Medicine’s tissue-based comprehensive genomic profiling test, FoundationOne CDx, was also approved as a companion diagnostic for olaparib in May 2020.


Foundation Medicine expands indication for FoundationOne Liquid CDx to be used as a companion diagnostic for Lynparza. News release. Foundation Medicine; November 9, 2020. Accessed November 9, 2020.

Enzalutamide Induces Added Benefit for Patients With Castration-Resistant Prostate Cancer

Researchers have found an added benefit in terms of mortality due to the longer overall survival with the drug enzalutamide (Xtandi) to treat adult patients with high-risk nonmetastatic castration-resistant prostate cancer, according to a reassessment by the German Institute for Quality and Efficiency in Health Care.

The drug had previously been examined twice, before in 2018 and 2019, to see if there was an advantage in comparison with the appropriate comparator therapy. Both the first and second data cut-offs for the PROSPER study found no added benefit for the drug to treat high-risk nonmetastatic castration-resistant prostate cancer.

In regard to morbidity and health-related quality of life, no new findings existed when compared with the first assessment of the drug. As a result, no added benefit was determined for these outcome categories.

Where that differed was in terms of mortality for the third data cut-off when compared with the first assessment. The data indicated that patients in the enzalutamide arm survived considerably longer than patients in the comparator arm.

The researchers explained that the results were mixed in terms of the drug’s adverse effects (AEs). For renal and urinary disorders, there were signs of a major AE advantage for patients, although it is unclear whether this reduced AE profile was a result of treatment or symptoms of the disease. More disadvantages were found for enzalutamide when compared with watchful waiting while maintaining ongoing conventional androgen deprivation therapy.

Regardless, the disadvantages did not put the advantages into question. The overall assessment found an added benefit for enzalutamide compared with the appropriate comparator therapy.


Castration-resistant prostate cancer at high risk of metastasis: enzalutamide has added benefit. News release. American Association for the Advancement of Science; August 19, 2020. Accessed November 14, 2020.

Lenvatinib in Combination With Pembrolizumab or Everolimus Shows Promise for Advanced RCC

New investigational data from the pivotal phase 3 KEYNOTE-581/CLEAR trial (Study 307) demonstrated that the combination of pembrolizumab (Keytruda) and lenvatinib (Lenvima) in patients with advanced renal cell carcinoma (RCC) met the study’s primary end point of progression-free survival (PFS) and its key secondary end points of overall survival (OS) and objective response rate (ORR).

The results, announced by Merck, demonstrated statistically significant and clinically meaningful improvements in PFS, OS, and ORR vs lenvatinib combined with sunitinib (Sutent) in the intention-to-treat (ITT) study population. Additionally, lenvatinib plus everolimus met the trial’s primary end point of PFS and a key secondary end point of ORR, demonstrating a statistically significant and clinically meaningful improvements in both vs the sunitinib combination in the ITT study population.

The safety profiles of both pembrolizumab plus lenvatinib and lenvatinib plus everolimus were found to be consistent with previously reported studies.

The multicenter, randomized, open-label, phase 3 trial is evaluating lenvatinib in combination with pembrolizumab or in combination with everolimus vs sunitinib for the first-line treatment of patients with advanced RCC. The primary end point is PFS by independent review per RECIST 1.1 criteria and key secondary end points include OS, ORR, and safety.

The study enrolled approximately 1050 patients who were randomized to 1 of 3 treatment arms to receive either:

  • 18 mg of lenvatinib orally once daily in combination with 5 mg orally once daily of everolimus; or
  • 20 mg of lenvatinib orally once daily in combination with 200 mg of pembrolizumab intravenously every 3 weeks; or
  • 50 mg of sunitinib orally once daily for 4 weeks on treatment, followed by 2 weeks off treatment.

The ITT population included patients across all Memorial Sloan Kettering Cancer Center risk groups, including favorable, intermediate, and poor.

Merck and Eisai indicated that they will discuss these data with regulatory authorities worldwide, with the intent to submit marketing authorization applications based on these results. In addition, they will be submitting the results to be presented at an upcoming medical meeting.

Of note, the companies are continuing to study the pembrolizumab plus lenvatinib combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program across 19 trials in 13 different tumor types, including endometrial carcinoma, hepatocellular carcinoma, melanoma, non–small cell lung cancer, RCC, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer, and triple-negative breast cancer.


Keytruda (pembrolizumab) plus Lenvima (lenvatinib) demonstrated statistically significant improvement in progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) versus sunitinib as first-line treatment for patients. News release. Merck; November 10, 2020. Accessed November 14, 2020.

Tremelimumab, Durvalumab Combo Shows Promise for Certain Patients with Localized Bladder Cancer

Phase 1 clinical trial results published in Nature Medicine demonstrated that neoadjuvant combination treatment with tremelimumab and durvalumab (Imfinzi) was well tolerated and showed early signs of activity in certain patients with localized bladder cancer who are not eligible for cisplatin-based chemotherapy.1

Patients included in the study had tumors with high-risk features that are associated with unfavorable outcomes, defined by bulky tumors, variant histology, lymphovascular invasion, hydronephrosis, and/or high-grade upper tract disease.

Between April 2017 and December 2018, researchers enrolled 28 patients with high-risk, cisplatin-ineligible, localized muscle-invasive urothelial carcinoma in the first cohort of the study. Participants had baseline transurethral resection of bladder tumor and were then treated with a combination of durvalumab at a dose of 1500 mg/kg and tremelimumab at a dose of 75 mg/kg every 4 weeks for a total of 2 combination doses before cystectomy.

No deaths related to therapy occurred. However, the majority of patients experienced an immune-related adverse event (irAE) of any grade. The most common irAE was grade 1 or 2 rash and asymptomatic increase in amylase; each occurred in 29% of patients. Additionally, the study did not exceed its safety or futility rules, with a total of 6 patients (21%) experiencing grade 3 or higher irAEs.

Of the 28 patients enrolled in the trial, 24 completed cystectomy per protocol, with 9 (37.5%) achieving a pathologic complete response (pCR). Moreover, in 12 patients with particularly large tumors (stage T3-T4), the pCR rate was 42%, with half of those patients seeing their tumor size reduced to stage T1 or less.2

Importantly, median overall survival (OS) has not yet been reached, and 24 patients were still alive at 1 year. Additionally, 82.8% of patients who had surgery were free of disease recurrence at 1 year.

The researchers also collected pre- and posttreatment blood and tissue samples from patients to study biomarkers associated with response, identifying higher-density tertiary lymphoid structures (TLS) in pretreatment tumor samples from patients who responded well to combination therapy compared with those who did not respond. Notably, a higher density of TLS correlated with longer OS and relapse-free survival.

Although these results still need to be confirmed in larger studies, investigators indicated that the findings suggest that TLS may act as an effective predictive biomarker for patients who will respond to checkpoint blockade.


1. Gao J, Navai N, Alhalabi O, et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nat Med. Published online October 12, 2020. doi:10.1038/s41591-020-1086-y

2. Dual checkpoint blockade promising as pre-surgical approach for certain patients with localized bladder cancer. News release. The University of Texas MD Anderson Cancer Center; October 12, 2020. Accessed November 14, 2020.

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