Phase 3 Randomized Controlled Trial of Post-Surgical Stereotactic Radiotherapy (SRT) versus Surgically Targeted Radiation Therapy (STaRT) with GammaTile for Treatment of Newly Diagnosed Metastatic Brain Tumors (ROADS; NCT04365374)

It is estimated that 20% to 40% of all patients with cancer develop brain metastases.1 In fact, it is estimated that 200,000 new cases of brain metastases are diagnosed each year.2 The size of the metastatic lesion often drives the treatment approach taken. Larger (>2 cm) symptomatic lesions that are in an accessible location are typically resected and the surgical bed is often treated with stereotactic radiotherapy (SRT). SRT improves local control over resection alone, with a rate of local recurrence-free survival of approximately 61% to 72% at 12 months,3,4 and has become the preferred standard of care.5

However, in patients who receive SRT treatment in the postoperative setting, radiation necrosis rates can be significant, with an incidence rate upward of 18.2%.6 There is an unmet need for an adjunctive radiation therapy approach that may improve the rate of surgical bed control without the inherent risk of brain injury to normal tissue. In addition, this new therapy lowers the incidence of hair loss as an adverse effect and does not negatively impact wound healing.

GammaTile (offered by GT Medical Technologies, Inc) is an FDA-cleared device that consists of four cesium-131 radiation-emitting seeds in a collagen tile approximately the size of a postage stamp. These tiles are used to line the brain cavity immediately after resection of the tumor. This approach to Surgically Targeted Radiation Therapy (STaRT) has a number of benefits, including an immediate start of radiation treatment after tumor resection when the disease burden is at a minimum (instead of having to wait 3 to 4 weeks until the surgical wound heals); optimization of radiation dosimetry, allowing the highest dose in the region of the tumor and a lower dose in normal surrounding tissue; and visible surgical bed tissue during the time of tile placement, allowing for precise targeting of radiation therapy. Additionally, patients do not need to return as an outpatient for radiation treatment.

The purpose of this trial is to compare surgical tumor removal followed by SRT against surgical tumor removal followed by STaRT utilizing GammaTiles. The primary end point is surgical bed recurrence-free survival. Secondary end points include overall survival, physical function, neurocognitive status, quality of life, and safety. ROADS is a multicenter randomized controlled trial funded by GT Medical Technologies (NCT04365374). The study opened for enrollment in April 2021.

Adult patients with 1 to 4 newly diagnosed brain metastases with 1 lesion (between 2.5 cm and 5.0 cm), the largest being called the index lesion and planned for surgical resection. Nonindex lesions must measure <4.0 cm. Previous and/or concurrent treatment with systemic therapies (eg, chemotherapy, targeted therapeutics, immunotherapy) is permitted. Patients must have a Karnofsky Performance Status score of ≥70 and have stable systemic disease or reasonable systemic treatment options predicting a life expectancy of ≥6 months. Patients must be fluent in the English language to allow for completion of neurocognitive tests. Past radiation or surgical therapy to the index lesion or the newly diagnosed nonindex lesion(s) is exclusionary. However, up to a total of 2 prior courses of SRT treatment to previously diagnosed lesions are allowed, as long as any treated lesions were greater than 15 mm from the index lesion.

Fourteen sites are at various stages of trial activation. A total of 4 sites are open to accrual: The University of Texas MD Anderson Cancer Center, Piedmont Healthcare, University of Texas Southwestern Medical Center, and Keck School of Medicine of the University of Southern California.

STUDY SCHEMA. R + SRT VERSUS R + GAMMATILE THERAPY

University of Texas
MD Anderson Cancer Center

1. Aoyama H, Shirato H, Tago M, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. 

. 2006;295(21):2483-2491. doi:10.1001/jama.295.21.2483

2. Arvold ND, Lee EQ, Mehta MP, et al. Updates in the management of brain metastases. 

. 2016;18(8):1043-1065. doi:10.1093/neuonc/now127

3. Brown PD, Ballman KV, Cerhan JH, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. 

. 2017;18(8):1049-1060. doi:10.1016/S1470-2045(17)30441-2

4. Mahajan A, Ahmed S, McAleer MF, et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. 

. 2017;18(8):1040-1048. doi:10.1016/S1470-2045(17)30414-X

5. NCCN. Clinical Practice Guidelines in Oncology. Central nervous system cancers, version 1.2021. Accessed July 13, 2021. https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf

6. Tanenbaum DG, Buchwald ZS, Jhaveri J, et al. Dosimetric factors related to radiation necrosis after 5-fraction radiosurgery for patients with resected brain metastases. 

. 2020;10(1):36-43. doi:10.1016/j.prro.2019.09.014

Articles

Clinical Trials in Progress: ROADS Trial

Early changes in the standardized uptake value corrected for lean body mass (SULmax) could be predictive of pathologic complete response (pCR) to pertuzumab (Perjeta) and trastuzumab (Herceptin) for patients with estrogen receptor–negative, HER2-positive breast cancer, according to findings from the phase 2 TBCRC026 study (NCT01937117) published in the 

Findings from the study identified a significant difference in median percent reduction in SULmax by C1D15 among patients who achieved pCR (63.8%) and those who didn’t (41.8%; 

=.004). Investigators also identified an estimated odds ratio (OR) of 1.03 that was associated with a 1% reduction of SULmax (95% CI, 1.01-1.06).

The ROC analysis, which utilized percent reduction in SULmax as the predictor, yielded an area under the curve of 0.72 (80% CI, 0.64-0.80; 

= .12); this did not reject the null hypothesis for the primary end point. The exploratory cutoff of40% or more vs less than 40% reduction in SULmax demonstrated a sensitivity of 83% and a specificity of 48% for identifying patients who achieved a pCR.

“In the TBCRC026 trial, we investigated whether early changes in SULmax on FDG-PET-CT can predict pCR after HER2-directed therapy with pertuzumab and trastuzumab alone (no chemotherapy) in ER-negative, HER2-positive early-stage breast cancer,” the investigators of the study said.

Investigators theorized that early measurement of SULmax through the use of 18F-labeled fluorodeoxyglucose (FDG) PET-CT may help predict potential pCR to pertuzumab and trastuzumab. All patients who enrolled on the study underwent baseline C1D15 and FDG-PET-CT.

The study enrolled 88 women at 9 different sites from January 2014 to August 2017. Only 83 were evaluable for the primary analysis, all of whom underwent primary surgery. In total, 85% of patients (n = 77/88) completed all 4 cycles of pertuzumab and trastuzumab. Additionally, 25 (28%) patients received neoadjuvant non-study therapy and did not obtain pCR. Additionally, 22 of these 25 patients had histologically confirmed residual disease after 12 weeks of pertuzumab and trastuzumab.

Other non-study neoadjuvant therapies included taxane and carboplatin–based therapy (n = 17) and taxane-based therapy with pertuzumab and trastuzumab (n = 7). One patient received a fifth cycle of pertuzumab and trastuzumab and 2 received anthracycline based neoadjuvant chemotherapy.

In total, pCR was achieved in 18 (22%) of patients after 4 cycles of pertuzumab and trastuzumab alone (95% CI, 13-22). Investigators assumed that the patients who withdrew consent did not obtain pCR, and they created an estimated of 18 (20%) of patients for pCR (95% CI, 13-32). Among patients who had confirmed residual disease or clinical progression after 12 weeks of the experimental regimen and achieved an additional neoadjuvant non-study treatment, 7 of 22 (32%) had pCR at the time of surgery. Additionally, 7 (8%) patients experienced clinical progression on pertuzumab and trastuzumab after 2 to 4 cycles of treatment. 

Investigators also identified a difference among the evaluable patients who experienced a change in median C1D15 SULmax and achieved a pCR and those who did not (1.6 vs 3.6; 

< .001). Additional findings from the ROC analysis identified an AUC of 0.77 (80% CI, 0.70-0.83; 

= .009). The cutoff of 3 or less vs over 3 yielded in C1D15 SULmax yielded a high negative predictive value for pCR over other cut points. A significantly higher proportion of C1D15 SULmax of 3 or less was noted in patients who obtained pCR compared with those who did not (100% vs 45%; 

Although the study did not meet its primary end point, early change in SULMax appeared to be predictive of the combination in this patient population. After undergoing optimization, this imaging strategy could be used to help better select patients for treatment with pertuzumab/trastuzumab.

Connolly RM, Leal JP, Solnes L, et al. Updated results of TBCRC026: phase II trial correlating standardized uptake value with pathological complete response to pertuzumab AND trastuzumab in breast cancer. 

. 2021;39(20):2247-2256. doi:10.1200/JCO.21.00280

Investigators identified that early changes in standardized uptake value corrected for lean body mass may be able to predict pathologic complete response to pertuzumab AND trastuzumab in patients with HER2-positive breast cancer.

Early Changes in SULmax Could Predict Pathological CR to Pertuzumab/Trastuzumab in HER2+ Breast Cancer 

Incidence of death by suicide was found to be significantly high in patients diagnosed with head and neck cancer (HNC), with a 50% higher incidence of suicide-related mortality for those living in rural areas vs urban and metropolitan areas, according to a study published in 

JAMA Otolaryngology-Head and Neck Surgery

The suicide mortality rate for patients with HNC living in rural areas was 126.7 per 100,000 person-years compared with 64.0 per 100,000 person-years in urban counties and 59.2 per 100,000 in metropolitan counties. In the general HNC population, investigators identified a notably higher risk of suicide in rural (Standardized mortality ratio [SMR], 5.46: 95% CI, 3.06-9.02), urban (SMR 2.84; 95% CI, 2.13-3.71), and metropolitan populations (SMR 2.78; 95% CI, 2.49-3.09).

“The objective of this study was to estimate suicide incidence and risk among patients with HNC based on rural versus urban or metropolitan residential status. Previous studies have shown that there is higher HNC incidence and mortality among patients from rural areas versus urban areas,” said investigators of the study.

The study used a sample of 134,510 patients with HNC. Of the population, 101,142 (75.2%) had an average age of 57.7 years. Patients in metropolitan areas comprised 86.6% of the study, urban residents were 11.7% and rural was 1.7%.

Within the group, there were 405 reported deaths by suicide. The majority of these patients were non-Hispanic (90.1%) and male (93.1%). Investigators determined the median time from diagnosis to suicide was 26 months (range, 0-203), while the median follow-up time for all patients was 41.0 months (range, 0-203).

Investigators used the unadjusted Fine-Gray models to determine that suicide mortality was highest among rural residents. Patients from urban (HR, 0.51; 95% CI, 0.28-0.92) and metropolitan (HR, 0.48; 95% CI 0.28-0.82) had approximately half the risk of dying by suicide. However, investigators reported that there was no difference in mortality between residents of urban and metropolitan areas (HR, 1.06; 95% CI, 0.78-1.42).

When accounting for covariates, the results were similar. When using the sub-distribuation HR (sdHR), residents of urban (sdHR, 0.52; 95% CI, 0.29-0.94) and metropolitan counties (sdHR, 0.55; 95% CI, 0.32-0.94) had about half the risk of suicide-related mortality vs patients residing within rural counties.

Investigators also used a regression model for inclusion of county-level income and education level and identified a slight decrease in the effect size relative to rural counties ( metropolitan sdHR, 0.62; 95% CI, 0.35-1.09; urban sdHR, 0.55; 95% CI, 0.30-1.00).

Th investigators emphasized the importance of developing a comprehensive understanding of the multilevel factors associated with suicide risk and that future suicide prevention strategies should have increased focus on rural health, quality of life, and mental well-being of survivors, including those with HNC.

“Future suicide prevention policies should have a specific focus on rural health. Although reducing the suicide rate is a national imperative and is considered a leading health indicator in the United States, evidence shows that rural health has not been specifically targeted by the current national strategy for suicide prevention. However, the evidence from the general literature as well as this study of the cancer site with the second-highest suicide mortality rate suggests that it is critical to specifically consider rural health when designing action plans for suicide prevention,” the investigators concluded.

Osazuwa-Peters N, Barnes JM, Okafor SI, et al. Incidence and risk of suicide among patients with head and neck cancer in rural, urban, and metropolitan areas. 

. Published Online July 23, 2021. doi:10.1001/jamaoto.2021.1728

Patients with head and neck cancer who live in rural counties are 50% more likely to die from suicide compared with individuals residing in urban or metropolitan areas. 

Suicide Risk Found to be Significantly High in Head And Neck Cancer, Especially in Rural Populations

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with Sara A. Hurvitz, MD, from the University of California, Los Angeles Jonsson Comprehensive Cancer Center, about utilizing sacituzumab govitecan (Trodelvy) for the treatment of older patients with metastatic triple-negative breast cancer (mTNBC).

Sacituzumab govitecan was examined in the phase 3 ASCENT study (NCT02574455) in patients with relapsed/refractory TNBC with subgroup analyses performed to assess the impact of age. The study found that regardless of age (≥65 or <65 years), patients who had received 2 or more chemotherapies had a significant survival benefit with use of sacituzumab govitecan.

It’s quite important for us as clinical investigators to explore outcomes based on age. We do have an aging population and cancer is a disease that, at least in breast cancer, increases [with patients who are] increasing in age. It is really important for us to look at outcomes based on age. From a geriatrician standpoint, I think they would support this type of analysis because treatment decisions across the board—whether it’s in cardiology, pulmonology, oncology, or endocrinology—should be based on a patient’s performance status and ability to accept therapy rather than a numerical age. I’m reassured that these data show a similar efficacy outcome with the use of sacituzumab as well as a reasonable safety profile. The data will make us all more comfortable offering this therapy that’s associated with a survival benefit to patients, regardless of their age. I’m sure geriatric oncologists applaud this type of analysis.

Kalinsky K, Oliveira M, Traina T, et al. Outcomes in patients (pts) aged ≥65 years in the phase 3 ASCENT study of Sacituzumab govitecan (SG) in metastatic triple negative breast cancer (mTNBC). 

. 2021;39(suppl 15):1011. doi: 10.1200/JCO.2021.39.15_suppl.1011

Videos

CancerNetwork® sat down with Sara A. Hurvitz, MD, at the 2021 ASCO Annual Meeting to talk about multidisciplinary care with geriatrician oncologists and the use of age-based analyses for diagnosis and following up of metastatic triple-negative breast cancer. 


Sara A. Hurvitz, MD, Discusses Outcomes With Sacituzumab Govitecan By Age for Metastatic Triple-Negative Breast Cancer

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with Sylvie Bonvalot, MD, PhD, from Institut Curie, about standard of care and treatment options for patients with high-grade or grade II sarcoma.

Bonvalot discusses a phase 2/3 trial (NCT02379845) that used the radioenhancer NBTXR3 as a preoperative treatment to radiotherapy for high-grade sarcoma. The findings of this study were positive and reinforced the use of NBTXR3 in patients with locally advanced soft tissue sarcoma.1 In her discussion, she talks about leaning on colleagues across multidisciplinary oncology teams to select patients who are appropriate for treatment.

In locally advanced sarcoma of at least high-grade or grade 2 [disease], the standard treatment is surgery and radiotherapy and more and more of this [is by] local treatment. Radiotherapy is delivered preoperatively because the long-term morbidity is lower than postoperative therapy. There was a trial run by O’Sullivan a few years ago and clearly preoperative radiotherapy had a better outcome in the long term; [however] you cannot do that for everyone.2

When there was indication and sufficient fit for appropriate radiotherapy, we do more of the radiotherapy postoperatively. This is for high-grade locally advanced sarcoma. Concerning chemotherapy, it’s not standard of care. They would debate, it depends on the subtype, but neoadjuvant chemotherapy is still an option in the guidelines; it’s not always the patient. Usually for grade II or III locally advanced sarcoma, standard of care is a radiotherapy and surgery and the option is a chemotherapy for a subgroup of patients with specific subtype, [such as a] young patient because classically it is a little bit difficult for elderly patients. It’s not the standard of care to deliver the chemotherapy for outpatient surgeries and why the standard is radiotherapy and surgery. In this trial we did, we’re discussing [patients] in the multi-disciplinary tumor board. When it was a locally advanced high-grade sarcoma, the conclusion was radiotherapy and surgery, and the trial was proposed to the patient.

1. Bonvalot S, Rutkowski P, Thariat J, et al. Long-term evaluation of the novel radioenhancer NBTXR3 plus radiotherapy in patients with locally advanced soft tissue sarcoma treated in the phase II/II Act.In.Sarc trial. . J Clin Oncol. 2021; 39(suppl 15):11544. 10.1200/JCO.2021.39.15_suppl.11544

2. O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002;359(9325):2235-2241. doi:10.1016/S0140-6736(02)09292-9

CancerNetwork® sat down with Sylvie Bonvalot, MD, PhD, at the 2021 ASCO Annual Meeting to talk about treatment options for high-grade or grade II sarcoma.

Sylvie Bonvalot, MD, PhD, Discusses Selecting Patients With Locally Advanced Sarcoma for Pre and Postoperative Treatment 

End-of-life (EOL) discussions such as advanced care, palliative care, and discontinuation of treatment are consistently being missed, according to a study published in 

; however, investigators highlighted existing strategies that are being utilized to achieve successful EOL conversations.

Investigators found that out of 423 outpatients encounters with 141 patients with advanced cancer, only 21 encounters (5%) included EOL discussions. When investigators included a random sample of 93 encounters, 35 encounters (35%) included missed opportunities for EOL conversations. Three patient/oncologist dyads had more than 1 encounter with a conversation pertaining to EOL, which translated to 17 of 141 dyads (12%) having at least 1 event of EOL discourse. The dyads included 13 of 39 oncologists (33%).

“In this secondary analysis of outpatient oncology visits, EOL discussions were rare and missed opportunities for these discussions were common. When oncologists did discuss EOL, they framed it around trade-offs, anticipatory guidance, and acknowledging patients as experts,” investigators of the study said. 

Investigators identified 3 strategies that are being used to navigate opportunities for successful EOL conversations:

Those who take advantage of opportunities for EOL discussions are able to reevaluate treatment options based on patients’ concerns, outlining the risks and benefits between treatment continuation and discontinuation. When suggesting chemotherapy for treatment, it is imperative to be transparent in letting patients know it could prolong survival, but there would be discomfort from adverse effects, the investigators stated. This allows the patients to make decisions about their own future.

Another strategy that has been utilized when making EOL decisions is allowing patients to be experts on their treatment decisions in order to meet their goals. This was accomplished by positing questions such as “What would you like?” and “What was the goal you would like to attain?”. By exploring a patient’s goals and allowing them to lead the conversation, the patient can shape treatment recommendations. Patients are able to explore their thoughts and feelings with regard to treatment discontinuation in a manner that is approachable. This allows one to act as a facilitator who creates an environment of reflection, while the patient shifts their focus to decision making.

The use anticipatory guidance to frame conversations pertaining to treatment reevaluation is another useful strategy. Anticipatory guidance can be used to identify a potential timeframe in which patients will need to make decisions regarding quality of life over cancer-directed treatments. During this time, it is the oncologist's responsibility to provide sign posts to convey when it may be time to consider quality of life over treatment. This helps patients set appropriates goals and limits as to when they might like to discontinue treatment.

There are a number of hurdles that lead to missed opportunities for or deflected EOL conversations, one of which including responding inadequately to patient concerns. Patients who are concerned about disease progression or dying are often met with partial, avoidant, or absent responses instead of opening the conversation about EOL, which limits the opportunity for patients’ conversations around goals, values, and preferences. Additionally, giving little to no response when a patient expresses fear at the idea of living for years with late stage disease could prevent the occurrence of conversations around disease burden, treatment decision making, and EOL care.

Although speaking about the future optimistically may seem helpful it does little to address patient concerns. Instead of using anecdotes about other patients who exceeded life expectancy, consider using that moment to realistically discuss the patient’s prognosis.

Additionally, expressing concern over patient’s decision to discontinue treatment could be another opportunity for a missed discussion. Although one might be able to justify their treatment decisions by stating that they are in line with the patient's goal, it is a missed chance for discourse pertaining to quality of life and treatment goals. Moreover, declaring a patient's next steps for treatment without holding a proper conversation is yet another missed opportunity wherein a conversation about the patient's options could have taken place.

“Although we recognize that not every patient or appointment may necessitate an EOL discussion, all patients in this study had stage IV malignant neoplasm and their oncologists had previously acknowledged that they ‘would not be surprised if they were admitted to an intensive care unit or died within one year.’ Despite the urgent necessity of EOL discussions within this population, we found far more missed opportunities than actual discussions in this analysis,” the investigators concluded.

Knutzen KE, Sacks OA, Brody-Bizar OC, et al. Actual and missed opportunities for end-of-life care discussions with oncology patients: A qualitative study. 

. 2021;4(6):e2113193. doi:10.1001/jamanetworkopen.2021.13193

Trends towards missing key moments for end-of-life discussions when meeting with patients who have stage IV cancer can be overcome with existing strategies for successful EOL conversations. 

Qualitative Study Shares Strategies for Successful End of Life Conversations for Patients With Cancer

A biologics license application for the novel long-acting granulocyte-colony stimulating factor (G-CSF) agent eflapegrastim (Rolontis) was issued a complete response letter by the FDA due to deficiencies in manufacturing, as reported by the company responsible for the agent, Spectrum Pharmaceuticals.1

The FDA indicated that a reinspection will be necessary and further clarification regarding these plans are being discussed between the 2 entities.

“We are disappointed with this outcome and look forward to fully understanding the remediation timelines for the program,” Joe Turgeon, president and CEO of Spectrum Pharmaceuticals, said in a press release. “We continue to believe in Rolontis and plan to diligently complete the regulatory process to bring Rolontis to market.”

Eflapegrastim is intended for use alongside myelosuppressive anticancer drugs and, if approved, would be the first novel G-CSF agent to become available to clinicians and their patients in over a decade. The BLA was supported by data from 2 phase 3 clinical trials investigating the safety and efficacy of the agent in patients with early-stage breast cancer receiving chemotherapy for their disease.

In the ADVACNE trial (NCT02643420), eflapegrastim was compared with pegfilgrastim in patients with early breast cancer who were receiving docetaxel and cyclophosphamide with a primary end point of severe neutropenia duration in cycle 1. In 406 patients in the intent-to-treat population, the mean duration of severe neutropenia (DSN) was 0.19 days (standard deviation [SD], 0.478) in the experimental arm vs 0.34 days (SD, 0.668) with pegfilgrastim and met the threshold for non-inferiority (95% CI, -0.260 to -0.035; 

 <.0001). Noninferiority was maintained across all 4 cycles.2

The RECOVER trial (NCT02953340) was conducted in a similar fashion to ADVANCE in 237 intent to treat patients, for which the mean DSN was 0.31 days (SD, 0.688) for eflapegrastim compared with 0.39 days (SD, 0.949) with standard pegfilgrastim (95% CI, -0.292 to 0.129; 

 <.0001), with noninferiority maintained across 4 cycles of therapy.3

In either trial, the statistical significance for additional end points such as time to absolute neutrophil count (ANC) recovery, depth of ANC nadir, and incidence of febrile neutropenia at cycle 1 were noted.

This BLA for eflapegrastim was initially submitted in October 2019, which was an update to a previously withdrawn application for this indication. The new BLA had additional information in the Chemistry, Manufacturing and Controls (CMC) section regarding the manufacturing process.4 In December 2019, the company announced that the new BLA had been accepted by the FDA with a prescription drug user fee act (PDUFA) date of October 24, 2020.5

1. Spectrum Pharmaceuticals receives complete response letter from FDA for Rolontis (eflapegrastim). News release. Spectrum Pharmaceuticals. August 6, 2021. Accessed August 6, 2021. https://bit.ly/3AiXbj2

2. Schwartzberg LS, Yang Z, Peguero JA, et al. Safety and efficacy of eflapegrastim in reducing severe neutropenia in patients treated with myelosuppressive chemotherapy in a phase 3 randomized controlled trial compared to pegfilgrastim (ADVANCE trial). 

 2018;36(suppl 15):e12513. doi:10.1200/JCO.2018.36.15_suppl.e12513

3. Schwartzberg LS, Bhat G, Mezei K, et al. Efficacy and safety of eflapegrastim confirmed in reducing severe neutropenia in breast cancer patients treated with myelosuppressive chemotherapy in the second phase 3 randomized controlled multinational trial compared to pegfilgrastim (RECOVER trial). 

. 2019;79(suppl 4):P1-13-05. doi: 10.1158/1538-7445.SABCS18-P1-13-05.

4. Spectrum Pharmaceuticals announces submission to the U.S. Food and Drug Administration of updated biologics license application for Rolontis. News release. Spectrum Pharmaceuticals. Published October 24, 2019. Accessed August 6, 2021. https://bit.ly/3fDAhv0

5. Spectrum Pharmaceuticals provides pipeline update on late stage programs. News release. Spectrum Pharmaceuticals. Published December 26, 2019. Accessed August 6, 2021. https://bit.ly/2VtM8EF

The makers of eflapegrastim received a complete response letter from the FDA due to concerns over manufacturing.

Complete Response Letter Issued to Eflapegrastim for Chemotherapy-Induced Neutropenia Indication

Within the Veteran’s Health Administration (VHA), race does not appear to influence the receipt of definitive treatment. However, Black men with prostate cancer were reported as receiving less definitive treatment in high-benefit situations than non-Black patients, according to the results of a study published in 

Findings from the study indicated that Black veterans with prostate cancer were 5% more likely to receive radiation therapy or surgery than non-Black patients (

 Additionally, veterans of all races who were likely to derive benefit from definitive therapy were 40% more likely to receive treatment than those who did not require it (

 <.001). Despite the advantages of advanced care that are currently available to this population of patients, Black men who were highly likely to derive benefit from treatment were 11% less likely to undergo treatment than non-Black patients of a similar age and disease severity (odds ratio, 0.89; 

“Our study suggests, for reasons that remain unclear, that Black men who need treatment may be choosing against the most beneficial prostate cancer therapies (which are often more invasive), or that such 'high-benefit' treatments, are not being offered to them as aggressively as they are to non-Black patients,” co-investigator Joseph Ravenell, MD, associate dean for diversity affairs and inclusion at New York University (NYU) Langone, associate professor at NYU Grossman School of Medicine, and co-leader of community outreach and engagement at the Perlmutter Cancer Center, said in a press release.

Previous findings have indicated that Black patients trend towards undergoing definitive prostate cancer treatments less than men of other races. However, it has yet to be seen as to whether this is due to avoidance of overtreatment in those with low-risk disease and avoid life-changing adverse effects such as erectile dysfunction and incontinence. Another reason for these disparities could be a reduction in appropriate care. This inspired the study’s investigators to examine the role of race in prostate cancer treatment benefit.

Investigators behind the retrospective cohort study identified 35,427 men through the VHA Corporate Warehouse who had been diagnosed with low- to intermediate-risk disease from 2011 to 2017. The majority who were included in the study were over the age of 60, were married, and had no notable comorbidities.

Men were characterized based on life expectancy and disease severity. For example, while a man in his 50s with aggressive disease who had undergone surgery or radiotherapy would be considered a high-benefit patient, older men with non-aggressive prostate cancer would be categorized as low benefit.

Additional findings from the study indicated that Black patients are more commonly diagnosed with prostate cancer 2 years earlier than patients of other racial groups of all ages. However, this population is more likely to be diagnosed with more aggressive disease. Additional research must be conducted to identify the forces that are responsible these racial disparities.

“Despite great strides in prostate cancer care over the past few decades, racial disparities in care persist, and there remains a lot to be done to better understand why this is happening and what we can do to finally close the gap. At the end of day, our goal is to offer patients the most appropriate cancer care they need, using a culturally sensitive approach,” Danil Makarov, MD, MHS, an associate professor in the Departments of Urology and Population Health at NYU Grossman School of Medicine, concluded.

Study sheds light on persistent racial disparities in prostate cancer care in the United States. News Release. NYU Langone Health. June 29, 2021. https://bit.ly/2VAt4V7

Rude T, Walter D, Ciprut S, et a. Interaction between race and prostate cancer treatment benefit in the Veterans Health Administration. 

. Published online June 29, 2021. doi: 10.1002/cncr.33643

Black veterans within the United States who could stand to highly benefit from definitive treatment were found to be less likely to undergo treatment than non-Black populations.

Black Veterans With Advanced Prostate Cancer Least Likely to Receive Beneficial Treatment, VHA Says

 Let’s go on to the next polling question. We’re going to transition to more quality-of-life types of things. How important do you think patient quality of life [QoL] is, compared with other considerations when selecting therapy for your patients with metastatic breast cancer? Not important, somewhat important, moderately important, very important? We should have the answers here soon. It looks like it’s very important for most of you and moderately important. Certainly no one should pick not important or somewhat important. It’s front and center on most of our minds. Dr Kaklamani, it’s routine and in vogue certainly to have quality-of-life data associated with your large clinical trials. How do you critically look at those data? Is it important that it comes from a phase 3 study? Is there value and stuff we learned from a phase 1 or 2 trial in terms of quality of life? How do you weigh the importance of the quality-of-life data?

 There’s value in anything, but obviously these data can be a subject of bias more than the data on response and PFS [progression-free survival]. Phase 3 trial data are extremely important. But honestly, it’s my experience when I treat 3, 4 patients with a specific medication. If I see bad toxicities regardless of everything I do, that probably taints my perception of that medication. People do get biased with their experience on medications, more about quality-of-life and toxicity than response rates.

 I totally agree with you: the more you use the drug, the better you get at handling it. The trial population is different from the patients we might take care of, different ECOG performance status, and so forth. Dr Iyengar, are there specific QoL data that patients bring up—not what you see but what they bring up—that comes up frequently, especially with some of the agents we’ve talked about tonight?

 There are toxicities that contribute to patient-reported outcomes and quality of life, like diarrhea, that we’re familiar dealing with, in terms of neratinib or tucatinib. Where you get into things like fatigue or general deconditioning, that can be a little more gray. We each have our own perspective or experiences with the various agents in terms of overall functioning of a patient. Some of the EORTC instruments that are reported in some of these trials—with regard to time to deterioration, for example—can be useful when interpreting the data and the maintenance of those functioning supports, perhaps with better patient-reported outcomes for an agent. It goes back to this practice and feel that folks get with a drug as Dr Kaklamani mentioned. Specific toxicity certainly contribute, but we have to listen to our patients.

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Calaspargase pegol (Asparlas) and pegaspargase yielded comparable results in terms of responses, activity, and safety in the treatment of pediatric and adolescent patients with newly diagnosed acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma, according to the results of a phase 3 trial (NCT01574274) published in the 

Of the evaluable patients who were included on the study (n = 239), 99% of those who were treated with pegaspargase and 95% of those who were treated with calaspargase achieved a complete response (

 = .12). Investigators did not identify a significant difference in frequency of high end–induction minimal residual disease between cohorts of patients with B-cell ALL (pegaspargase, 11%; Calaspargase, 10%; 

 = .99). After a median follow-up of 5.3 years, the 2 drugs yielded event-free survival rates of 84.9% and 88.1%, respectively (

 = .65), as well as a 5-year overall survival rate of 95.8% and 94.0%, respectively (

“Our results suggest that calaspargase may feasibly be used during induction therapy, without excess toxicity or significant impact on end-induction response,” wrote the investigators. “Given its longer half-life, calaspargase can be dosed less frequently than pegaspargase, especially in regimens that aim to achieve prolonged asparagine depletion.”

Those who enrolled were randomized to receive intravenous pegaspargase (n = 120) or calaspargase (n = 119) at 2500 IU/m2 per dose, with patient received 1 induction dose. At week 7, pegaspargase was given to patients every other week for 15 doses and calaspargase was given every 3 weeks for 10 doses. Serum asparaginase activity (SAA) was assessed by investigators on days 4, 11, 18, and 25 following the induction dose and prior to the postinduction dose.

Patients included in the study were between the ages of 1 to 21 years old with newly diagnosed disease. Most patients had ALL (n = 230) with a minority of patients presenting with lymphoblastic lymphoma (n = 9).Patients had a median age of 5.2 years (range, 1.0-20.9).

Additional findings from the study indicated that, following the induction dose, SAA was 0.1 IU/mL or greater in over 95% of patients across both arms 18 days after dosing. However, 88% of patients in the calaspargase arm had an SAA of 0.1 IU/mL or more versus only 17% in the pegaspargase arm by day 25 (

 <.001). It was also found that the median nadir SAAs were comparable postinduction in both groups of patients.

Vrooman LM, Blonquist TM, Stevenson KE, et al. Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia: results of DFCI 11-001. 

. Published online July 6, 2021. doi:10.1200/JCO.20.03692

Pediatric and adolescent patients with acute lymphoblastic leukemia experienced similar outcomes when treated with either calaspargase pegol or pegaspargase. 

ONCOLOGY Vol 35, Issue 7 | August 2021

Clinical Trials in Progress

Clinical Trials in Progress: GOZILA

Original Research

Comparing GOZILA and COLOMATE: Ongoing Umbrella/Basket Trials Examining Genetic Testing in Gastrointestinal Malignancies

Review Article

Level of Scientific Evidence Underlying the National Comprehensive Cancer Network Clinical Practice Guidelines for Hematologic Malignancies: Are We Moving Forward?

Review Article

Profilin 1 Protein and Its Implications for Cancers

Review Article

Combination Therapy With Immune Checkpoint Inhibitors in Urothelial Carcinoma: Current Data and Future Outlook

Case Study

Median Lobe Urethral Embolus After Focal Ablation of Gleason 7 Prostate Cancer

Clinical Quandaries

Advanced Penile Cancer Presenting With Renal Failure

Editorial

The Future of Telehealth for Hematology/Oncology Care