There has been substantial evolution in the treatment of metastatic renal cell carcinoma with notable changes in the first-line setting. Currently, doublet combination therapy with either two immune ...checkpoint inhibitors or a combination of an immune checkpoint and tyrosine kinase inhibitor is considered the standard of care. The doublet combination therapies have demonstrated significantly improved clinical outcomes. A recently conducted trial (COSMIC-313) showed superior efficacy with a triplet combination of cabozantinib, nivolumab, and ipilimumab when compared to a placebo, nivolumab, and ipilimumab but at the cost of additional toxicity. Many other combination treatments, such as pembrolizumab plus lenvatinib plus belzutifan (NCT04976634), are being investigated, possibly leading to more options in the first-line setting in the future.
Metastatic urinary tract cancer (mUTC) is challenging to treat in older adults due to comorbidities. We compared the clinical courses of younger and older (≥70 years) adults with mUTC receiving ...first-line (1L) systemic therapy in a tertiary cancer center. Baseline clinical characteristics, treatments received, tolerability, and survival outcomes were analyzed. Among 212 patients (103 older vs. 109 younger), the older patients had lower hemoglobin at baseline (84% vs. 71%, p = 0.03), the majority were cisplatin-ineligible (74% vs. 45%, p < 0.001), received more immunotherapy-based treatments in the 1L (52% vs. 36%, p = 0.01), received fewer subsequent lines of treatment (median 0 vs. 1, p = 0.003), and had lower clinical trial participation (30% vs. 18%, p = 0.05) compared to the younger patients. When treated with 1L chemotherapy, older patients required more dose adjustments (53.4% vs. 23%, p = 0.001) and received fewer cycles of chemotherapy (median 4 vs. 5, p= 0.01). Older patients had similar OS (11.2 months vs. 14 months, p = 0.06) and similar rates of treatment-related severe toxicity and healthcare visits, independent of the type of systemic treatment received, compared to younger patients. We conclude that select older adults with mUTC can be safely treated with immunotherapy and risk-adjusted regimens of chemotherapy with tangible survival benefits.
A 64-year-old man presented with symptoms indicative of superior vena cava syndrome. Imaging work-up revealed an obstructing right atrial mass, which was subsequently excised and diagnosed as primary ...cardiac lymphoma. Post-surgery, the patient showed significant clinical improvement and was started on a chemotherapy regimen with complete remission at 1 year.
Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious
and/or
mutations. ...Identifying patients with prostate cancer harboring these mutations may be challenging. Circulating cell-free DNA (cfDNA) provides an avenue for an easier detection of these mutations. Herein, we aimed to evaluate the concordance of
mutations in the tumor tissue and cfDNA in patients with metastatic prostate cancer in the real-world setting.
Somatic genomic profiling results were obtained from a clinical cohort of patients at our institution who had at least two samples tested. One of the samples needed to be from either primary or metastatic tissue. Concordance was adjusted to not include mutation types that the cfDNA platforms were not designed to detect.
The presence or absence of mutations in the
gene was assessed in a total of 589 samples, including 327 cfDNA samples, from 260 patients with metastatic prostate cancer. The median time between the first test and any subsequent test was 22.8 (0.0-232) months.
mutation was present in the patient's original prostate tissue in 23 samples (3.9%) of patients. The adjusted concordance between prostate tumor tissue and cfDNA was 97.9% 95% CI, 95.3-99.1%. The adjusted concordance between metastatic samples and cfDNA was 93.5% 95% CI, 86.4-97.3%. Of the patients who had a
mutation detected in their prostate tissue, there was a 70% probability of detecting a
mutation in the patient's cfDNA as well. For patients who did not have a detectable
mutation in their primary prostate tissue, the probability of detecting a subsequent one later in the disease course was less than 0.9%.
There is a high level of concordance between tissue and blood for
mutations. Testing cfDNA can provide reliable information on
mutational status and is a viable alternative to solid tissue sequencing when unavailable. The development of a new
mutation later in the disease course is a rare event.
This commentary remarks on the study conducted by Lu et al, which contributes to the existing knowledge on translocation renal cell carcinoma (tRCC) by examining how race may influence susceptibility ...to tRCC and how distinct transcriptomic profiles among different races may explain variations in tRCC prognosis.
This commentary highlights 2 international studies on real-world treatment trends and patterns among patients with metastatic castration-sensitive and resistant prostate cancer and how interventions ...targeting physicians and patients can bridge the gap between evidence-based medicine and real-world practice.
To date, immune targeting agents have provided limited benefits in patients with metastatic prostate cancer. Bispecific T-cell engagers, especially targeting STEAP1, have shown encouraging results in ...preclinical and phase I studies and thus represent a novel and promising treatment option in this setting. See related article by Nolan-Stevaux et al., p. 90 (7). See related article by Kelly et al., p. 76 (8).
Abstract
Background
DNA damage repair genes alterations (DDRa) are frequent events in renal cell carcinoma (RCC), including BAP1 and other DDRa. Olaparib is a poly ADP ribose polymerase inhibitor ...(PARPi) that is FDA-approved for the treatment of several malignancies with DDRa. Preclinical models demonstrated synthetic lethality with PARPi in RCC cell lines including BAP1 mutant lines. Here we report an interim analysis of the ORCHID study investigating the clinical activity of single agent olaparib in patients (pts) with advanced RCC (aRCC) harboring BAP1 other select DDRa.
Methods
We conducted a single center, single arm, investigator-initiated Phase 2 trial of olaparib in pts with aRCC. Eligible pts harbored select DDRa and had prior therapy with immune checkpoint inhibitors (ICIs) and/or VEGF-TKI. Pts were treated with olaparib at an initial dose of 150mg twice which was increased to 300mg twice daily after one month if well tolerated. The primary endpoint is disease control rate (DCR) by RECIST v1.1 (including complete response (CR), partial response (PR), and stable disease (SD) >6 months). Secondary endpoints included objective response rate (ORR), progression free survival (PFS), and safety.
Results
Eleven pts were enrolled with a median age of 59 years (48-72) including 9 pts with clear cell RCC and 2 pts with unclassified RCC. Most pts had BAP1 mutations (Table). 36% of pts had history of brain metastasis. Median number of prior lines of therapies was 2 (1-6) and all pts received prior ICI. The study met the pre-specified Simon’s 2 stage design for the first stage with 22% DCR in the evaluable pts (2/9), including deep PR (>70% reduction in tumor volume) and SD of 10 months. Both pts harbored BAP1 mutations. An additional pt with BRCA1 mutation had 20% decrease in measurable disease. There were no treatment related adverse events resulting in study discontinuation.
Conclusions
This is the first study investigating single agent PARPi in RCC with the interim trial analysis indicating promising activity of olaparib in aRCC pts with BAP1 mutations including one pt with deep PR. These results support further development of PARPi in this setting.
