Patients with metastatic breast cancer experienced superior progression-free survival (PFS) after receiving targeted therapy matched to genomic alterations identified through multigene sequencing compared with patients who received maintenance chemotherapy, according to a pooled analysis of findings from the randomized phase 2 SAFIR02_BREAST (NCT02299999) and SAFIR-PI3K (NCT03386162) trials, which were presented during the 2021 San Antonio Breast Cancer Symposium (SABCS).

These trials assessed the impact of multigene sequencing, classified in the I/II tiers of the ESMO Scale of Actionability of Molecular Targets (ESCAT), in consequent targeted therapy.

The results showed that among 115 patients who had an ESCAT I/II genomic alteration, the median PFS was 9.1 months (90% CI, 7.1-9.8) with matched targeted therapy vs 2.8 months (90% CI, 2.1-4.8) with maintenance chemotherapy (adjusted HR, 0.41; 90% CI, 0.27-0.61, 

“These findings suggest that genomics should be a part of the pathway of care, but it has no impact if the results are not interpreted using a validated framework of actionability of the gene alterations identified,” lead study author Fabrice André, MD, PhD, professor of medical oncology at the Institut Gustave Roussy in Villejuif, France, said in a press release, which was accompanied by a virtual press briefing ahead of the conference.

“Multigene sequencing has been widely implemented, but its clinical impact and the best framework for its use are unclear. The main purpose of our study was to test whether genomic analyses are useful for patients with metastatic breast cancer, and how we can best analyze the results,” André said.

To that end, the open-label, multicentric, phase 2 SAFIR02_BREAST and SAFIR-PI3K trials enrolled patients with HER2-negative metastatic breast cancer who were eligible for first- or second-line chemotherapy.

-mutated metastatic breast cancer were randomized to the PI3Kα-specific inhibitor alpelisib (Piqray) plus the estrogen receptor antagonist fulvestrant (Faslodex) or maintenance chemotherapy.

In both trials, patients who had received more than 1 line of chemotherapy or 1 of the targeted therapies evaluated in the trial were excluded from enrollment. If patients had hormone receptor–positive disease, they had to have endocrine-resistant disease.

Patients underwent a pretreatment biopsy of the metastatic lesion, which was followed by next-generation sequencing and SNP array analysis.

After 6 to 8 cycles of induction chemotherapy, patients without evidence of disease progression (n = 238 of 1462; 16%) who had an actionable genomic alteration were randomized to matched targeted therapy (n = 157) or maintenance chemotherapy (n = 81).

The targeted therapy drugs and matching targets consisted of vistusertib for mTOR, AZD4547 for 

, bicalutamide (Casodex) for the androgen receptor, olaparib (Lynparza) for PARP, and alpelisib for 

The primary end point of the study was to determine whether genomically-driven targeted therapy improved PFS vs maintenance chemotherapy.

Hierarchical testing was applied such that efficacy was tested first in patients who had an ESCAT I/II alteration. If a 

 value of less than 0.1 was reported in the first analysis, subsequent analysis was conducted in the intent-to-treat population.

ESCAT classification is defined as follows:

Tier I: Alteration-drug match is associated with improved outcomes in clinical trials

Tier II: Alteration-drug match is associated with antitumor activity, but the magnitude of benefit is unknown

Tier III: Alteration-drug match is suspected to improve outcome based on clinical trial data in other tumor types or with similar molecular alterations

Tier IV: Preclinical evidence of actionability

Tier V: Alteration-drug match is associated with objective response, but without clinically meaningful benefit

Tier X: Lack of evidence for actionability

Additional findings reinforced that ESCAT classification was highly predictive for the benefit of matched targeted therapy (interaction test, 

 = .004). Notably, matched targeted therapy was not effective in patients without an ESCAT I/II alteration (HR, 1.15; 95% CI, 0.76-1.75).

Further findings failed to show a significant difference in PFS between the targeted therapy and chemotherapy arms in the overall population, with a median PFS of 5.5 months (90% CI, 4.0-6.9) vs 2.9 months (90% CI, 2.3-4.8), respectively (adjusted HR, 0.77; 95% CI, 0.56-1.06; 

Additional findings showed that the SNP array analyses (n = 926) detected 21 genes more commonly altered in metastases vs primary tumors. Of these, focal 

amplifications were associated with a poor outcome. Focal 

 amplifications were found after resistance to CDK4/6 inhibitors.

Finally, high homologous recombination deficiency was associated with prolonged PFS in patients with 

 mutations who had received olaparib (HR, 0.32; 95% CI, 0.12-0.83; 

“The general implication of our study is that precision medicine can improve patient outcome if it is interpreted with the right tools,” André said.

“I cannot overstate how important this clinical trial is,” Virginia Kaklamani, MD, a professor of medicine in the Division of Hematology/Oncology at UT Health San Antonio and leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center, and SABCS codirector and moderator of the press briefing added following André’s presentation of the data.

“This is the first trial that we have where we have used genomic alterations to actively change a patient’s treatment plan and found an improvement in the patient’s outcome. This is for early-stage breast cancer patients, which is even more important because the whole point [of treatment] is to try to prevent metastatic disease,” Kaklamani continued.

“What we’re trying to do and what Dr. André showed so eloquently was that by finding changes in the tumor that were unique to that patient and by having targeted therapies available for that change, we were able to treat the patient with that specific targeted therapy instead of standard of care, which would have been chemotherapy, and improve the patient’s outcome. This [tool] is something that we’re going to be using more and more in practice, [so that we’re] really treating our patients based on [their] genomic alterations,” Kaklamani concluded.

André F, Gonçalves A, Filleron T, et al. Clinical utility of molecular tumor profiling: results from the randomized trial SAFIR02-BREAST. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract GS1-10.

Articles

Patients who received matched targeted therapy specific to their genomic alteration, as identified through multigene sequencing, experienced significantly improved progression-free survival. 

Targeted Therapy With Multigene Sequencing Shows Superior PFS Vs Chemotherapy in Metastatic Breast Cancer

Pelvic organ-preserving robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion allowed most female patients to return to sexual activity following surgery without risking compromised oncological outcomes, according to retrospective findings presented at the 22nd Annual Meeting of the Society of Urologic Oncology.

In a virtual presentation shared during the meeting, study author Etienne Lavallee, MD, a urology fellow at the Icahn School of Medicine at Mount Sinai, said that the multicenter analysis included sexually active females undergoing pelvic organ–preserving RARC. Women had ≤pT2, N0, M0 urothelial cancer as determined by examination, imaging, and pathological staging. All patients had unifocal tumors away from the bladder base. Patients were excluded from the analysis if they had multifocal, trigonal, or locally advanced disease (>cT2) with potential internal genital organ involvement.

Sexual and urinary function after surgery was the primary study end point. To evaluate this end point, patients completed a sexual function questionnaire and the investigators used patient records from follow-up visits to assess urinary function. Secondary end points included perioperative and oncological outcomes.

Overall, the study included 23 female patients who underwent pelvic organ–preserving RARC. The surgeries were performed at 2 academic institutions between 2008 and 2020. Twenty (87%) patients underwent intracorporeal neobladder reconstruction and 3 (13%) patients received Ileal conduit urinary diversion.

The median patient age was 54 years (range, 34-79) and the median body mass index (BMI) was 23.6 kg/m (range, 18.2-33.1). Twelve patients were current smokers, 7 were former smokers, and 4 were never-smokers. The clinical stages were Tis/Ta/T1 (n = 10) and T2 (n = 13); the pT stages were T0 (n = 11), Tis/Ta/T1 (n = 2), T2 (n = 7), and T3 (n = 3); and the pN stages were pN0 (n = 19) and pN1(n = 3).

Seven patients had prior Bacillus Calmette-Guérin and 13 had neoadjuvant chemotherapy. The average operating time was 300 minutes (range, 250-390 minutes) and the average hospital stay was 6 days (range, 3-16). Eight patients had grade 1/2 surgical complications. There were no grade 3 to 5 surgical complications.

At a median follow-up of 20 months (range, 7-151), about two-thirds (65%; n= 15) of the patients completed the postoperative sexual function questionnaire. Of these patients, 87% (n = 13) resumed sexual activity within a median time of 6 months following surgery. Of these 13 patients, 8% (n = 1), 54% (n = 7), and 38% (n = 5) reported having low, moderate, and high levels of sexual activity, respectively. Orgasm during sexual activity was able to be achieved by all of the sexually active patients.

“Of the 10 patients who participated in penetrative intercourse, only 1 had occasional pain,” noted Lavallee.

Among patients who received neobladder reconstruction, 70% (n = 14) achieved daytime continence and 80% (n= 16) achieved nighttime continence.

“Half of the patients who underwent neobladder needed occasional clean intermittent catheterization,” added Lavallee.

Four (17%) patients had disease recurrence. The median time to recurrence was 13 months (range, 11-28). The recurrence-free survival rate was 83%. The cancer-specific survival and overall survival rates were both 91%. Two patients died of bladder cancer at 20 and 36 months, respectively.

“Of note, only 1 patient had a positive surgical margin, located at the left ureter. This was not considered to be due to the selection of an organ-preserving approach,” said Lavallee.

In his concluding remarks, Lavallee said, “Pelvic organ–preserving robot-assisted radical cystectomy with intracorporeal urinary diversion should be considered in selected sexually active women who wish to preserve sexual function after surgery.

1. Etienne Lavallee E, Dovey Z, Pathak P, et al. Female pelvic organ preserving robot-assisted radical cystectomy; functional outcomes of a modern robotic technique. Presented at: 2021 Society of Urologic Oncology Annual Meeting; November 30-December 3, 2021; Orlando, FL. Abstract 52.

A retrospective study presented at the 22nd SUO Annual Meeting revealed that pelvic organ–preserving robot-assisted radical cystectomy allowed women to return to sexual activity post-surgery. 

Women Who Receive Organ-Sparing Robotic Cystectomy Experience Preserved Sexual, Urinary Function

Findings presented at the 22nd Annual Meeting of the Society of Urologic Oncology demonstrated that patients with localized prostate cancer (PCa) and a body mass index (BMI) equal to or greater than 33 kg/m

 were less likely to undergo surgery (RP) as a treatment modality.

Nathan Samora—who presented the results and is a fourth-year medical student at Vanderbilt University School of Medicine—and fellow researchers sought to study the association between BMI and treatment modality as well as patient-reported outcomes after therapy.

The researchers found that men who were younger, less-educated, Black or had more comorbidities were more likely to be obese (

 <.001). Additionally, there was no significant difference in PCa risks across BMI groups.

Results demonstrated a linear increase in the likelihood of receiving an RP as the BMI increased from 18 to 28 and there was a linear decrease of receiving an RP thereafter. This became statistically significant at a BMI of greater than or equal to 33, Samora said. At no BMI was the likelihood of receiving active surveillance (AS) statistically significant.

Additionally, it was found that obese men have worse sexual function at baseline and all other time points throughout the 5 years; however, it was observed that trajectories between normal weight and overweight men are highly similar.

After adjusting for disease specifications between obese and non-obese men, it was found that there were not clinically important differences in patient-reported outcomes for men who underwent definitive treatment.

Results also demonstrated that men who were obese and on active surveillance had worse urinary incontinence compared with non-obese peers at 6 months and through the 5 years.

Patients (n = 2378) included were from the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) Study and were mostly White (77%), with a median age of 64 years and a median BMI of 27 kg/m

. Patient-reported quality of life was measured at enrollment and 6, 12, 36, and 60 months using the 26-item Expanded Prostate Index Composite (EPIC-26).

1. Samora, N, Wallis, C, Tallman, J, et al. Association between BMI and localized prostate cancer treatment modality and patient-reported outcomes. Presented at: Society of Urologic Oncology 22nd Annual Meeting; November 30-December 3, 2021; Orlando, FL. Abstract 105.

Researchers identified a linear decrease in the likelihood of surgery once patients with localized prostate cancer reached a BMI of 33 or greater.

High BMI in Localized Prostate Cancer Associated With Decreased Likelihood of Undergoing Surgery

Results presented at the 22nd Annual Meeting of the Society of Urologic Oncology indicate that the rates of upgrading and adverse pathology at radical prostatectomy cancer are similar in Hispanic and non-Hispanic men with prostate cancer.

“Hispanics are the largest ethnic minority and one of the most rapidly growing populations in the United States and prostate cancer is the highest incident non-cutaneous malignancy in this population,” said Helen Y. Hougen, MD, SUO fellow at the University of Miami, during a presentation of the findings. However, compared with other well studied populations, such as White non-Hispanic or Black men, the Hispanic or Latino population as a whole has been studied to a lesser extent, either it's combined with disparate groups or excluded altogether.”

Researchers sought to examine a rate and pattern of upgrading (any increase in Gleason grade [GG] from biopsy to prostatectomy) and adverse pathology (extraprostatic extension, seminal vesicle invasion, lymph node-positive) in Hispanic patients using an institutional prostatectomy database, specifically in the south Florida region.

Previously, the SEER database has demonstrated there are similar survival outcomes between Hispanic and White patients with prostate cancer; however, this database does not include South Florida—which has a high population of Hispanic men.

Patients included in the study were non-Hispanic White (NHW; n = 688), Hispanic White (HW; n = 736), and Black (n = 426) men who underwent a radical prostatectomy between 2014 and present. There was no significant difference in age, body mass index (BMI), prostate-specific antigen (PSA), prostate size, or biopsy GG between groups.

Results demonstrated that 651 patients had upgrading, and it was not different between groups.

On the univariable analysis, patients who were Black had a lower rate of adverse pathology compared with patients who were White. Hougen explained this may be because the Black population in south Florida has a greater number of men who are of Caribbean decent, not of African origin.

In the multivariable analysis, significant predictors for upgrading included older age, higher PSA, and lower prostate weight. And there were no differences observed between the three groups and the rate of upgrading.

Adverse pathology odds increased with older age, higher PSA, higher BMI, lower prostate weight, increased number of biopsy cores, and higher GG.

“Hispanic (patients) are more negatively impacted by socioeconomic factors, such as neighborhood effects, compared (with White patients). However, despite this, they have similar survival compared with white (patients) suggesting an at least equal, if not more favorable, cancer characteristic,” Hougen concluded.

Hourgen H, Iakymenko O, Punnen S, et al. Race is not associate with prostate cancer upgrading in Hispanic men undergoing radical prostatectomy. Presented at: Society of Urologic Oncology 22nd Annual Meeting; November 30-December 3, 2021; Orlando, FL. Abstract 148

Hispanics are the largest ethnic minority and one of the most rapidly growing populations in the United States. Prostate cancer represents the highest incident non-cutaneous malignancy in this population.

Rates of Upgrading, Adverse Pathology Similar in Hispanic and White Non-Hispanic Men With Prostate Cancer

Lindsay Fischer is the Associate Editor at ONN. She joined MJH life sciences in 2021 after graduating from Rutgers University with majors in both English and Spanish and a minor in creative writing. When she is not writing, or researching the latest oncology nursing news, Lindsay is an amateur backpacker and rollerblader. Email Lindsay at lfischer@mjhlifesciences.com

The majority of patients with prostate cancer adjusted their androgen deprivation therapy (ADT) post-scan management plan after receiving a 18F-fluciclovine PET/CT scan, according to findings presented at the 22nd Society of Urologic Oncology Annual Meeting.

Moreover, after the scans identified lesions, plans were commonly amended to target salvage therapy and spare patients the morbidity associated with ADT, said investigators.

Specifically, a total of 93 out of 146 patients (64%) had a change in management plan following their scans. The scan results also caused 55 patients (59%) to no longer have ADT included in their care plan. Furthermore, only 25% of patients who initially had a plan to receive ADT as a monotherapy still had a plan for ADT monotherapy post 18F-fluciclovine PET/CT.

“The advent of highly sensitive molecular imaging has allowed the identification of men with oligometastatic disease to may be more optimally treated with metastasis directed therapy than with systemic treatments, such as androgen deprivation therapy,” explained Gerald L. Andriole, Jr., MD, Division of Urologic Surgery, Department of Surgery, and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, in a presentation of the findings. “So, the goal of this particular study was to evaluate the impact of 18F-fluciclovine PET scans on plans to use androgen deprivation therapy in patients with biochemical recurrence.”

Investigators performed a secondary analysis of 2 treatment alteration studies: LOCATE (NCT02680041) and FALCON (NCT02680041). Out of the 317 patients with biochemical recurrence (BCR) enrolled in these studies, 146 had ADT, either as a monotherapy or in combination with another treatment modality, included in their post-scan plan.

PET/CT detection rates for prostate/prostate bed region; pelvic and extra-pelvic lymph nodes (LN); and soft tissues and bones, were determined at a per-patient level. The post hoc analysis compared post-scan treatment plans with pre-scan treatment plans and used imagining findings to stratify the data.

Sixty patients in the study were initially planned to receive ADT as a monotherapy, while 86 were initially going to receive ADT with another modality. Overall, lesions were detected in 85 patients (58%) who were planning to receive ADT. Lesions were detected in prostate/bed, pelvic LN, extra-pelvic LN, and soft tissue and bones, at rates of 30%, 25%, 13%, 2.1% and 13%, respectively.

Findings revealed that 25 patients (17%) had positivity that was limited to the prostate/prostate bed, 21 patients (14%) had 18F fluciclovine–positive pelvic nodes, and 39 patients (27%) had positive detection beyond the prostate/bed and pelvic nodes.

Notably, patients with the most disseminated disease (extra-pelvic involvement,12/30; 40%) were the patients who were likely to have a post-scan plan for ADT monotherapy. In contrast, patients with a negative scan were most likely to have a modified post-scan plan which aborted ADT (14/54; 26%). Among those whose post-scan plan aborted ADT, local disease was common.

“So, in summary, data from two prospective trials indicate that 18F-fluciclovine significantly influences the management plans for a majority of patients who had a pre-scan plan that included androgen deprivation therapy,” concluded Andriole. “Androgen deprivation therapy was aborted in about 40% of the patients originally intended to receive that and management plans were commonly amended to target salvage metastasis directed treatment to 18F-fluciclovine PET/CT abnormalities, and this spared the patients the morbidity associated with androgen deprivation therapy.”

1. Andriole GL, Scarsbrook AF, Davis P, Chaglassian A, et al. Impact of 18f-fluciclovine PET/CT on plans for ADT in patients with biochemical recurrence of prostate cancer; data analysis from 2 prospective clinical trials. Presented at: Society of Urologic Oncology 22nd Annual Meeting; November 30-December 3, 2021; Orlando, FL. Abstract 144.

A secondary analysis of 2 treatment alterations studies demonstrated that 18F-fluciclovine PET/CT scans play a pivotal role in determining if androgen deprivation therapy is appropriate for patients with prostate cancer. 

18F-fluciclovine PET/CT Significantly Influences ADT Plans for Patients with Prostate Cancer

Pembrolizumab has been approved for the adjuvant treatment of adults and pediatric patients with stage IIB or IIC melanoma who have underwent complete resection.

FDA Oks Adjuvant Pembrolizumab for Adult and Pediatric Melanoma Following Complete Resection

A study presented at the 22nd SUO Annual Meeting did not identify any significant or clinically meaningfully differences in HRQOL in patients with nonmetastatic bladder cancer who receive robotic-assisted vs open radical cystectomy. 

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Urine cytology specimen NGS was found to be a feasible and valid method of assessing genomic alterations in patients with upper tract urothelial carcinoma.

Urine Cytology NGS Comparable to Tumor Biopsy in Identifying UTUC Mutations 

A presentation at the SUO Annual Meeting underscored best surveillance strategies for patients with low-grade upper tract urothelial carcinoma who have undergone radical nephroureterectomy.

Smoking and Large Tumor Size Linked With Risk of Early Recurrence Post-Radical Nephroureterectomy in Low-Grade UTUC 

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High BMI in Localized Prostate Cancer Associated With Decreased Likelihood of Undergoing Surgery

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