Colleen Moretti 

In patients with metastatic castration resistant prostate cancer (mCRPC), sabizabulin (VERU-111) was well tolerated and associated with significant and durable objective tumor responses, according to phase 1b/2 clinical trial (NCT03752099) results presented at the 2021 ESMO Congress.

Both phases of the study consisted of patients who were previously treated with at least 1 androgen receptor-targeted therapy. The aim of the study was to evaluate the safety, maximum tolerated dose, and efficacy of sabizabulin.

Patients included in the study were advanced in their treatment, Mark C. Markowski, MD, PhD, medical oncologist from John Hopkins University in Baltimore, Maryland, highlighted during his presentation. Many patients had previously been treated with abiraterone acetate (Zytiga), enzalutamide (Xtandi), a combination of both, or apalutamide (Erleada) or proxalutamide.

The phase 1b portion used a 3+3 design in 39 patients (median age, 74 years). Initially, each dose was administered orally on days 1-7 on a regimen of every 21 days. If this regimen was well tolerated and considered safe, the frequency was increased to a daily dosing on days 1-14 every 21 days. And if that was tolerated, patients then advanced to dosing daily until disease progression or toxicity.

In the phase 1b portion of the study, 10 patients reached at least 4 cycles of continuous dosing. Of that 10, 6 had any PSA response, 2 had at least a 50% PSA response. Additionally, two patients had a partial response, with the remaining 8 achieving stable disease. The median radiographic progression-free survival (rPFS) was greater than 12 months (range, 6.0-28+ months). And as of August 2021, 2 of the 10 patients remained on the study.

“That’s the most mature data we have. (It’s) a bit difficult given our dose escalation strategy,” Markowski noted.

The open-label phase 2 portion of the study comprised 44 patients (median age, 73 years) and evaluated the recommended dose of 63 milligrams (mg) daily. “We found that (the) recommended phase 2 dose was 63 milligrams per day, so daily dosing was safe and feasible,” Markowski explained.

The most common adverse events among 54 patients included diarrhea, fatigue, ALT and AST increases, all of which were mostly grade 1 and 2. Markowski added that there were no reports of clinically relevant neutropenia or neurotoxicity, “which we’ve seen before with taxane chemotherapy.”

Objective response rate in the intention-to-treat population (n = 26) was 20.7%, with 5 partial responses and 1 complete response. And in evaluable patients who qualified for a future phase 3 trial (n = 26) it was 23.1%.

In patients that received at least 63 mg (n = 55) median rPFS is estimated to be at least 7.4 months.

Markowski detailed that a phase 3 trial, known as VERACITY (NCT04844749), is currently underway and is evaluating 32 mg of sabizabulin for the treatment of mCRPC against an alternative AR-targeting agent. Patients in this study had prior treatment with 1 AR-targeted therapy, and no chemotherapy. This trial has a primary endpoint of rPFS.

Markowski M, Eisenberger M, Tutrone R, et al. Sabizabulin, an oral cytoskeleton disruptor, to treat men with metastatic castration resistant prostate cancer who failed an androgen receptor targeting agent. Presented at 2021 ESMO Congress; September 16-21, 2021; virtual. 578MO.

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In patients with metastatic castration resistant prostate cancer, sabizabulin was well tolerated and associated with significant and durable objective tumor responses

Sabizabulin Appears Effective and Safe in Metastatic Castration Resistant Prostate Cancer

Future studies on genitourinary (GU) cancer may be limited as many currently lack data on how smoking impacts outcomes in this patient population, according to a systematic review presented at the 2021 AUA Annual Meeting. 

“This study highlights a deficiency in urologic oncology [randomized, controlled trials’] to assess smoking status and participants. Given smoking’s effects on treatments, survival, and quality of life, we believe this is an important area that deserves more attention,” said Calvin C. Zhao, MD, New York University School of Medicine, during a virtual presentation at the meeting.

The primary outcome of this review was whether a study collected and reported data on their participants smoking status. Secondary outcomes included details on how smoking status was reported, if trial arms were balanced, and if smoking status was included in the analysis.

Using PRISMA guidelines, researchers identified 622 articles and 354 later met criteria to be used in the review. Only 8.2% (n = 30) of studies reported on smoking. Of those, 27 studies reported smoking in the manuscript or supplement. And 96.3% of studies reported at baseline qualitatively, such as “never,” “former,” or “current”, instead of quantifying pack-years or intensity.

Only 3 studies reported final or subgroup analyses that included smoking. And of that, 2 reported significant differences in outcomes that were associated with smoking status.

No study reported a smoking measurement instrument, non-cigarette tobacco use, and changes in smoking status over time. 

Studies had to be published between May 2010 and May 2020; were randomized phase 2 through 4 trials; reported in the top 10 medicine, urology, or oncology journals by 2018 Impact Factor; reported primary analysis on data; must be a therapeutic intervention; and patients had to have had prostate, urothelial, or kidney cancer.

Studies included were mostly trials in prostate cancer (n = 210), were published in the 

 (n = 81), included patients from multiple continents (n = 119), reported on systematic therapies (n = 166), had an endpoint of overall survival (n = 102), and included patients with metastatic disease (n = 172).

Limitations of this study include the timeline allowing for the inclusion of older articles, a publication bias for more positive and later stage trials, and journal scope.

“However, we believe our search strategy adequately captured the most impactful and landmark trials in contemporary urologic oncology literature,” Zhao said. “Until we have a better understanding of the tobacco use patterns of our patients, we cannot fully characterize the effects of smoking on cancer outcomes.”

Future directions should be using validated and standardized instruments to measure smoking status such as the Cancer Patient Tobacco Use Questionnaire (C-TUQ). As well as, report smoking status through the entire study period, integrate the data into Electronic Medical Record and smoking cessation counseling. Zhao said integrating these practices will allow for a “more robust analysis” of interactions between tobacoo use and clinical trial outcomes

“Ultimately, we believe there is a great need for more rigorous attention to smoking in urologic cancer patients. The way forward, we believe, is for urologists to play a more active role in not just smoking assessment, but also smoking cessation,” Zhao concluded.

Matulewicz R, Zhao C, Myrie A, et al. A systematic revies and scoping analysis of smoking cessation after a urologic cancer diagnosis. Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract LBA02-01.

Future studies on genitourinary cancer may be limited as many currently lack data on how smoking impacts outcomes in this patient population. 

A ‘More Active Role’ is Needed From Urologist in Reporting Smoking Assessment, Cessation in Clinical Trials

In men with prostate cancer undergoing prostatectomy, a phase 2 study has shown that yoga may help improve quality of life, promote an antitumor immune response.

A presentation given during the American Urologic Association 2021 Annual Meeting.

Explained that yoga has a direct effect on the vagus nerve, which can shape how a person thinks, remembers, and feels. And patients with prostate cancer have a 20% to 30% incidence and prevalence of depression and anxiety.

In previous studies, yoga has demonstrated an improved quality of life for patients with cancer, as well as lower inflammation. Additionally, newer, emerging data has demonstrated that mindfulness exercises, such as yoga, can cause the frontal and limbic parts of the brain to structurally change.

“However, if you look at hierarchy of evidence, most data on immune benefits of yoga is from small series and case reports, no such data exists for prostate cancer. Given these findings of improvement in quality of life with yoga, we started looking at [the] role of yoga in prostate cancer,” said Dharam Kaushik, MD, associate professor in the department of urology at the University of Texas Health, San Antonio, during the presentation of the data.

The primary outcomes of this clinical trial [NCT02620033] was self-reported outcomes of quality of life at baseline, and 6 weeks. Secondary outcomes included immune cell status and cytokine levels, also at baseline and 6 weeks.

“We wanted to evaluate the quality of life from multiple vantage points, therefore we utilized 4 different quality of life questionaries,” Kaushik mentioned. Self-reported outcomes were assessed by the Expanded Prostate Index Composite (EPIC), Functional Assessment of Cancer Therapy-Prostate (FACT-P), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Five Facets of Mindfulness Questionnaire (FFMQ).

The study consisted of 30 men who were newly diagnosed with localized prostate cancer and scheduled for a radical prostatectomy. Patients were randomized to either yoga (n = 15) or standard of care (n = 15). And patients in the yoga group, performed the activity for 60 minutes twice a week for 6 weeks before their prostatectomy and 3 to 6 weeks after.

Yoga “meaningfully” improved EPIC-sexual scores, FACIT-F, FACT general and FACT-P. In substratification, there were improvements in sexual, physical, and social well-being in the yoga group.

Additionally, participants in the yoga group demonstrated increased numbers of CD4+ (

There was also an increase in the natural killer cells IFNNK (

 = .041), “indicating a robust immune response,” Kaushik added.

Yoga also had an enhanced effect on antitumor activity, decreasing the numbers of regulator T-cells and myeloid-derived suppressor cells: CD11b+CD33+ (

There was also a decrease in cytokine cells including, G-CSF (

 = .032), which had shown to activate production endothelial cell and cytokines. Additionally, there was a decrease in MCP-1 (

 = .044), which are associated with proception against dementia, and FLt-3L (

 = .053) which has been linked to reducing chronic inflation, Kaushik mentioned.

The benefits demonstrated in this study require further investigation, the authors concluded in the abstract.

Kaushik D, Shah P, Mukherjee N, et al. A phase 2 randomized clinical trial of yoga in men with prostate cancer. Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract LBA02-03.

Phase 2 research highlights a wellness modality that may improve outcomes in men with prostate cancer.

Wellness Modality May Improve QoL and Immune Responses in Patients with Prostate Cancer

John Gribben, MD, DSc, FRCP, FRCPath, FMed Sci

Axicabtagene ciloleucel (axi-cel; Yescarta) improved outcomes for patients with relapsed/refractory follicular lymphoma (R/R FL) over currently available therapies, according to data from a comparative analysis of the ZUMA-5 (NCT03105336) and SCHOLAR-5 trials.

Improvements were seen in objective response rate (ORR), progression-free survival (PFS), time to next treatment (TTNT) and overall survival (OS), the presentation at the 2021 European Hematology Association (EHA) Virtual Conference showed.

“ORR, [complete response], PFS and TTNT comparisons showed statistically significant improvements highlighting deep and durable treatment effect of axi-cel in this patient population,” said study author John Gribben, MD, DSc, a professor of medical oncology at Cancer Research UK Barts Centre, in a presentation of the findings.

Researchers sought to compare outcomes from an updated 18-month analysis of the ZUMA-5 trial to a matched sample of patients from the SCHOLAR-5 external control cohort.

The study authors analyzed 85 patients from the SCHOLAR-5 cohort, and 86 patients from ZUMA-5.

Patients included in this study had to have grade 1-2 R/R FL and have failed 2 or more previous lines of treatment as well as have an ECOG score of 0 or 1. After propensity score weighting, baseline characteristics in ZUMA-5 included a median age of 62 years (range, 34-79 years), 48 males (55.8%), 49 patients whose disease progressed within 24 months of first-line chemoimmunotherapy [POD24] (57%), 3.6 prior lines of treatment, 63 patients refractory to prior line (73.3%), 21 patients with a prior SCT (24.4%), 8.44 months since time of last treatment, 76.05 months since diagnosis, 51 patients with ECOG score of 0 (59.3%) and 35 patients with an ECOG score of 1 (40.7%).In SCHOLAR-5, the baseline characteristics included a median age of 61 years(range, 36-89 years), 53 males (61.9%), 47 POD24 patients (55.9%), 3.53 prior lines of treatment, 65 patients refractory to prior line of treatment (76.6%), 24 patients with a prior SCT (28%), 7.74 months since time of last treatment, 82.24 months since diagnosis, 21 patients with an ECOG score of 0 (29%) and 51 patients with an ECOG score of 1 (71%).

ORR among the patient population was substantially higher in the ZUMA-5 trial (94.2%) than in the SCHOLAR-5 trial (49.9%; OR = 16.24; 95% CI, 5.63-46.85; 

< .0001). Moreover, complete responses were significantly improved in the ZUMA-5 cohort (79.1%) than in the SCHOLAR-5 cohort (29.9%; OR = 8.86; 95% CI, 4.3-18.25; 

A median PFS was not reached in the cohort from ZUMA-5, whereas it was 12.68 months in the SCHOLAR-5 cohort (

< .001). Additionally, a median OS was not reached in the ZUMA-5 cohort; however, median OS in the SCHOLAR-5 cohort was 59.8 months (

“The substantial overall survival benefit seen in this study suggest that axi-cel addresses an important unmet medical need for relapsed/refractory follicular lymphoma patients,” said Gribben.

Median TTNT also significantly favored the ZUMA-5 cohort (not reached) over the SCHOLAR-5 cohort (14.43 months) (

Of note, neither a median OS, PFS or TTNT were met in a primary and subgroup analysis of ZUMA-5.

“This data certainly supports that axi-cel represents a significant improvement in treatment options for patients with relapsed/refractory follicular lymphoma,” Gribben concluded.

Based on findings from the phase 2 ZUMA-5 trial, the FDA approved axi-cel for the treatment of this patient population in March 2021.

Ghione P, Patel A, Bobillo, S, et al. A comparison of clinical outcomes from ZUMA-5 (axicabtagene ciloleucel) and the international SCHOLAR-5 external control cohort in relapsed/refractory follicular lymphoma (R/R FL). Presented at: 2021 European Hematology Association Congress; June 9-17; Virtual. Abstract LB1904.

Axicabtagene ciloleucel improved outcomes for patients with relapsed/refractory follicular lymphoma over currently available therapies, according to data from a comparative analysis of the ZUMA-5 and SCHOLAR-5 trials.

Axi-Cel Outperforms Alternate Treatments in R/R Follicular Lymphoma

Consistent efficacy was seen with selpercatinib (Retevmo) in patients with 

 fusion-positive non-small cell lung cancer (NSCLC), regardless of prior treatments, according to findings from the LIBRETTO-001 trial (NCT03157128) presented at the virtual 2021 ASCO Annual Meeting.

“(The) results, (however), should be interpreted with caution, as a limitation of this analysis was that immediate prior response assessment was based on physician-reported best response in patients’ medical history and may not follow RECIST criteria,” the study authors wrote in the poster. 

The study was conducted across 89 sites in 16 countries and consisted of 218 evaluable patients (median age, 61 years) who previously received platinum-based chemotherapy. Most patients had an ECOG score of 0/1 (37%/61%) and received a median of 2 (range, 1-15) prior systematic therapies. The study’s primary endpoint was objective response rate (ORR), with additional endpoints of progression-free survival (PFS), duration of response (DOR) and safety.

The study compared physician reported best overall response (BOR) from last systematic therapy received prior to enrollment with selpercatinib BOR by independent review committee, and each patient served as their own control.

The ORR with selpercatinib was 57% which was “markedly higher,” the authors wrote, than responses with prior treatment which was 16%.

A total of 108 patients (50%) did not respond to prior therapy but responded to treatment with selpercatinib. There were 16 patients (7%) who responded to both selpercatinib and prior therapy, 18 patients (8%) who responded to prior therapy but not selpercatinib and 76 patients (35%) who did not respond to either.

ORR was improved regardless of prior therapy, chemotherapy plus immune checkpoint inhibitor (ICI) (57% versus 14%), single-agent ICI (48% versus 3%) or chemotherapy (58% versus 15%).

Fewer patients had progressive disease with selprecatinib BOR (2%), compared with immediate prior therapy (28%). Median DOR was also notably longer compared with prior therapy, 11.8 months versus 3.4 months.

The authors concluded noting that the global, randomized phase 3 LIBRETTO-431 trial (NCT04194944) evaluating selpercatinib compared with standard frontline therapy (pemetrexed/carboplatin with or without pembrolizumab [Keytruda]) is ongoing.

Drilon A, Gautschi O, Besse B, et al. Response to selpercatinib versus prior systematic therapy in patients (pts) with 

 fusion + non-small cell lung cancer (NSCLC). 

Consistent efficacy was seen with selpercatinib in patients with RET fusion-positive non-small cell lung cancer, regardless of prior treatments. 

Selpercatinib May be an Effective NSCLC Treatment 

Treatment with aumolertinib led to improved progression free survival (PFS) and duration of response (DOR) in patients with advanced non-small cell lung caner (NSCLC) with epidermal growth factor receptor (EGFR), compared with gefitinib (Iressa), according to data presented during the 

“Based on these results, we will pursue discussions with global regulatory authorities; we anticipate our development approach will facilitate a markedly less costly global access pricing structure,” said Shun Lu, from the Shanghai Lung Cancer Center, Shanghai Chest Hospital at Shanghai JiaoTong University, in the presentation.

Aumolertinib is an irreversible EGFR tyrosine kinase inhibitor (TKI) that has already been approved in China for patients with EGFR mutant NSCLC when disease has progressed and has favorable pharmacologic properties that inhibit EGFR sensitizing and resisting mutations.

This phase 3 trial assessed the safety and efficacy of treatment with aumolertinib compared to gefitinib in 429 patients across China who had previously untreated metastatic or locally advanced NSCLC and EGFR exon 19 deletion or L858R. Patients were randomly assigned to received either aumolertinib, once per day at 110mg (n= 214; median age, 59 years), or gefitinib, once per day at 250mg (n = 215; median age, 62 years). Researchers had a primary endpoint of (PFS), and secondary endpoints of overall survival (OS), objective response rate (ORR), DOR and safety. With 262 PFS events the study had 90% power to detect PFS (HR = 0.67).

Median PFS was significantly prolonged with aumolertinib at a median of 19.3 months (HR = 0.46; 95% CI, 17.8-20.8; 

 < 0.0001) compared with gefitinib at 9.9 moths (HR = 0.46; 95% CI, 8.3-12.6; 

Median DOR followed a similar trend and was also significantly prolonged by aumolertinib at 18.1 months (HR = 0.38; 95% CI, 15.2-NA; 

 < 0.0001) compared with gefitinib at 8.3 months (HR = 0.38; 95% CI, 6.9-11.1; 

 < 0.0001). ORR was 73.8% with aumolertinib and 72.1% with gefitinib. And median overall survival was not reached.

Although aumolertinib was a longer treatment time compared to gefitinib, 463 days versus 254 days, side effects such as rash, diarrhea, alanine aminotransferase/ aspartate aminotransferase increase were less likely in that group.

The most common adverse events included alanine aminotransferase increased (29.4% in the aumolertinib arm vs 55.8% in the gefitinib arm), aspartate aminotransferase increased (29.9% vs 54%, respectively), rash (23.4%, vs 41.4%), diarrhea (16.4% vs 35.8%) and creatine phosphokinase (CPK) increased (35.5% vs 9.3%).

Additionally, aumolertinib was also associated with CPK increased, platelet count decrease and neutrophil count decrease.

Further research evaluating aumolertinib with other treatments is either ongoing or planned, Lu noted.

Lu S, Dong X, Jian H, et al. Randomized Phase III Trial of Aumolertinib (HS-10296, Au) Versus Gefitinib (G) as First-Line Treatment of Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) and EGFR Exon 19 Del or L858R mutations (EGFRm). 

Treatment with aumolertinib led to improved progression free survival and duration of response in patients with advanced non-small cell lung caner with epidermal growth factor receptor, compared with gefitinib.