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

Loyda E. Braithwaite, MSN, RN, AGPCNP-BC, AOCNP, an oncology nurse practitioner at the University of Wisconsin Carbone Cancer Center, provides an overview of the evolving treatment landscape in hormone receptor–positive breast cancer. Braithwaite highlights the emerging role of selective estrogen receptor degraders, selective estrogen receptor modulators, and updates on aromatase inhibitors within the space. She also discusses the management of potential treatment-emergent toxicities and how recently approved agents might make active treatment more accessible for certain patient populations.

“Decision-making doesn’t happen spontaneously,” Braithwaite says. “[There] are strong data and scientific research that show new therapies are emerging. It is up to us, as advanced providers, or as nurses, to make sure that we provide that education and that support [to our patients], because the evidence is out there.”

, please consider subscribing to our podcast on Apple Podcasts, Spotify, Google Podcasts, Amazon Music, and many of your other favorite podcast platforms, to get a notification every time a new episode is posted. While you are there, please take a moment to rate us!

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Loyda E. Braithwaite, MSN, RN, AGPCNP-BC, AOCNP, highlights nursing considerations in prescribing and administering endocrine therapy to patients with HR+ breast cancer. 

Loyda Braithwaite Discusses Evolving Treatment Options in HR+ Breast Cancer 

Patients with breast cancer that harbors 

 fusions achieved deep and durable responses following treatment with entrectinib (Rozlytrek), according to updated data from the phase 2 STARTRK-2 trial (NCT02568267) presented at the ESMO Breast Cancer Congress 2022.

At a median duration of survival follow-up of 35.3 months in patients with 

 fusion–positive disease (n = 7), entrectinib elicited a 71% (95% CI, 29.0%–96.3%) overall response rate (ORR); 2 patients achieved a complete response (CR) and 3 patients had a partial response (PR). Response data were missing on the other 2 patients. Both patients who achieved a CR had secretory disease, and among the 3 patients to have a PR, 2 had secretory disease and 1 had non-secretory disease. Among the 5 responders, the median duration of response (DOR) was 12.9 months (95% CI, 4.2-not evaluable [NE]).

 gene fusions are drivers in many solid tumors, including breast cancer.

 Though less than 1% of all breast cancer cases harbor 

 fusions, they are present in more than 90% of secretory breast carcinomas.

Prior data from the ALKA-372-001 trial (EudraCT 2012-000148-88), the phase 1 STARTRK-1 trial (NCT02097810), and STARTRK-2 showed entrectinib demonstrated deep and durable responses in patients with 

 Prior data from STARTRK-2 showed patients with 

 fusion–positive breast cancer achieved an ORR of 83% (n = 5 of 6), a median DOR of 12.9 months (95% CI, 4.2-NE), a median progression-free survival (PFS) of 10.1 months (95% CI, 5.1-NE), and a median overall survival (OS) of 23.9 months (95% CI, 5.1-23.9).

STARTRK-2 enrolled patients with locally advanced or metastatic solid tumors that harbored an 

 fusion–positive breast cancer. Moreover, patients were eligible regardless of central nervous system (CNS) metastases, and patients were required to be naïve to TRK inhibitors.

Enrolled patients received 600 mg of entrectinib once daily. Tumor burden was assessed following the first cycle of therapy, followed by every 8 weeks after by blinded independent central review per RECIST v1.1 criteria. Notably, regular brain scans were required for patients with baseline CNS metastases.

The primary end points were ORR and DOR per blinded independent central review. Secondary end points included PFS, OS, intracranial efficacy, CNS progression, and safety.

 fusion–positive breast cancer, all were female with a median age of 61 years (range, 36-67), and 5 patients were White. Patients had an ECOG performance status of 0 (n = 3), 1 (n = 2), or 2 (n = 2). All patients had received prior chemotherapy, radiotherapy, and hormonal therapy, and 5 patients were administered prior targeted therapy. One patient had previous radiotherapy of the brain.

Prior lines of therapy for metastatic disease included 0 (n = 3), 1 (n = 1), 3 (n = 1), and 4 or more (n = 2). Two patients presented with CNS metastases at baseline, and the median time since diagnosis for all patients was 130.1 months (range, 32.6-309.1). Histology included non-secretory (n = 2), secretory (n = 4), and not specified (n = 1).

Additional data showed the median PFS was 10.1 months (95% CI, 5.1-NE), and the median OS was 19.2 months (95% CI, 5.1–NE).

In the 2 patients with CNS metastases at baseline, the first had HER2-positive, estrogen receptor (ER)–positive, PGR-negative disease and received whole brain radiation 2-6 months prior to beginning entrectinib. This patient received no prior lines of systemic therapy for metastatic disease, and she achieved a PR and an intracranial non-CR and non–progressive disease. The second patient had HER2-negative, ER-positive, PGR-positive disease and received 6 prior lines of systemic therapy for metastatic disease. This patient did not have response data after dying 1.7 months following the first dose of entrectinib, though her death was not considered related to treatment.

Notably, no patients experienced a CNS progression event, regardless of baseline status.

Among 12 patients who received at least 1 dose of entrectinib and were evaluable for safety, 4 patients experienced a grade 3 or higher treatment-related adverse effect (TRAE). These included anemia (n = 2), fatigue (n = 1), and increased alanine aminotransferase (n = 1). There were no grade 5 TRAEs recorded. Only 1 patient had a series TRAE.

The most common TRAEs of any grade included dizziness (n = 5), nausea (n = 5), anemia (n = 4), constipation (n = 4), vomiting (n = 4), dysgeusia (n = 3), diarrhea (n = 3), increased alanine aminotransferase (n = 3), increased aspartate aminotransferase (n = 3), increased blood creatinine (n = 3), paresthesia (n = 3), and increased weight (n = 3).

Treatment-related adverse events resulted in the dose interruptions in 6 patients, dose reductions in 5 patients, and treatment discontinuations in 1 patient.

“In line with previous reports, entrectinib was associated with a manageable safety profile in patients with 

 fusion-positive breast cancer,” lead study author Min Janice Lu, MD, of USC Norris Comprehensive Cancer Center, wrote in the poster.

Lu J, Blakely CM, Barve M, et al. Entrectinib in NTRK fusion-positive (NTRK-fp) breast cancer: updated data from STARTRK-2. Presented at: 2022 ESMO Breast Cancer Congress; May 3-5, 2022; Berlin, Germany. Poster 173P.

Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. 

. 2015;5(1):25-34. doi:10.1158/2159-8290.CD-14-0765

Wu S, Shi X, Ren X, Li K, Pang J, Liang Z. Evaluation of NTRK gene fusion by five different platforms in triple-negative breast carcinoma. 

. 2021;8:654387. doi:10.3389/fmolb.2021.654387

Demetri GD, Braud FD, Drilon A, et al. Updated integrated analysis of the efficacy and safety of entrectinib in patients with NTRK fusion-positive solid tumors. 

. 2022;28(7):1302-1312. doi:10.1158/1078-0432.CCR-21-3597

Lu J, Blakely CM, Le Tourneau C, et al. Efficacy and safety of entrectinib in NTRK fusion-positive (NTRK-fp) breast cancer. Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; Virtual. Abstract PS11-28.

Basket study of entrectinib (RXDX-101) for the treatment of patients with solid tumors harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK gene rearrangements (fusions) (STARTRK-2). ClinicalTrials.gov. Updated May 3, 2022. Accessed May 11, 2022. 

https://clinicaltrials.gov/ct2/show/NCT02568267

This article was originally published on OncLive as “Entrectinib Continues to Yield Promising Data in NTRK Fusion–Positive Breast Cancer”

Articles

Entrectinib elicited encouraging responses in patients with breast cancer that harbors NTRK fusions, according to updates from the phase 2 STARTRK-2 trial.

Entrectinib Generates Favorable Outcomes in NTRK Fusion+ Breast Cancer

VB10.16, a first-in-class, off-the-shelf therapeutic cancer vaccine, yielded promising initial responses in patients with HPV16-positive advanced cervical cancer who were heavily pretreated and who were also receiving atezolizumab (Tecentriq), according to interim results from the phase 2 VB C-02 trial (NCT04405349) that were announced by Nykoke Therapeutics.

At a median follow-up of 6 months in 39 patients, data showed VB10.16 plus atezolizumab elicited an overall response rate (ORR) of 21%, including a complete response (CR) in 2 patients and a partial response (PR) in 6 patients. The disease control rate (DCR) was 64%.

“These interim results support Nykode’s unique approach of targeting antigen-presenting cells (APCs), designed to produce a robust and long-lasting CD8 killer T-cell response against cancer cells. We look forward to reporting updated efficacy data readouts from the phase 2 trial during the first half of 2023 as we continue to advance our cervical cancer program,” Michael Engsig, chief executive officer of Nykode Therapeutics, stated in a press release.

The single-arm, multicenter, open-label VB C-02 trial enrolled female patients who were at least 18 years of age with advanced or recurrent nonresectable HPV16-positive cervical cancer, including squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma. Patients were required to have failed or be ineligible for systemic chemotherapy, radiotherapy, or other standard-of-care treatment.

Other eligibility criteria included a biopsy to assess PD-L1 status at screening; measurable disease per RECIST v1.1 criteria; recovery from the effects of surgery, radiation therapy, or chemoradiotherapy; an ECOG performance status of 0 or 1 at screening; and a life expectancy of at least 6 months per the best judgement of the investigator.

The primary end points of the study were incidence and severity of adverse effects (AEs), and ORR per RECIST v1.1 criteria. Secondary end points include duration of response, progression-free survival (PFS), overall survival, and the evaluation of immunogenicity of VB10.16 in combination with atezolizumab by analyzing HPV16 E6/E7-specific cellular immune responses.

Additional data from the interim results showed VB10.16 and atezolizumab elicited responses irrespective of PD-L1 status. In patients with PD-L1–positive disease, the ORR was 27% with a DCR of 77% compared with an ORR of 17% with a DCR of 58% in patients with PD-L1–negative disease. Patients with non-inflamed tumors had a DCR of 71%.

Per the press release, immunological analyses of the peripheral T-cell responses showed an increased HPV16-specific IFNγ T-cell immune response following vaccination in most subjects. These responses were associated with clinical efficacy, and the clearance of circulating HPV16 DNA was significantly correlated with clinical response and PFS, pointing to circulating tumor DNA as an early marker of response to treatment in cervical cancer.

After previously reporting positive interim safety data from the trial, this interim data found VB10.16 was generally safe and well tolerated. Notably, 10% of patients experienced grade 3 or higher treatment-related AEs, indicating no increased toxicity compared with atezolizumab monotherapy.

“The patients who were treated with VB10.16 in combination with atezolizumab in the C-02 trial were heavily pretreated and are prone to progress quickly. It is very encouraging to see that a majority of patients experienced a clinical benefit and that many patients had durable responses. The combination of VB10.16 and atezolizumab was also well tolerated by patients,” principal trial investigator Peter Hillemanns, MD, PhD, director of the Departments of Gynecology, Obstetrics and Breast Cancer at Hannover University Hospital in Germany, stated in a press release.

The VB C-02 trial is fully enrolled to date, with 52 patients across Europe.

Nykode Therapeutics announces positive interim results from its phase 2 trial with VB10.16 in combination with immune checkpoint inhibitor atezolizumab in advanced cervical cancer. News release. Nykode Therapeutics. May 9, 2022. Accessed May 10, 2022. 

Investigating the combination of VB10.16 and atezolizumab in patients with HPV 16-positive cervical cancer. ClinicalTrials.gov. Updated February 23, 2022. Accessed May 10, 2022. 

https://clinicaltrials.gov/ct2/show/NCT04405349

This article was originally published on OncLive as “VB10.16 Plus Atezolizumab Elicits Responses in HPV16-Positive Cervical Cancer”

Atezolizumab in conjunction with VB10.16, the first off-the-shelf therapeutic cancer vaccine, elicited encouraging responses in pretreated patients with HPV16-positive advanced cervical cancer.

Off-the-Shelf Cervical Cancer Vaccine Shows Promising Initial Results in HPV16+ Patients

Encouraging objective response rates (ORRs) were observed in patients with non–clear cell renal cell carcinoma (RCC) harboring prominent papillary features who received a combination of cabozantinib (Cabometyx) and nivolumab (Opdivo) according to findings from a phase 2 trial (NCT03635892) that were published in the 

At a median follow-up of 13.1 months, cabozantinib and nivolumab achieved an ORR of 47.5% (95% CI, 31.5%-63.9%) in patients in cohort 1 with papillary, unclassified, or translocation-associated RCC (n = 40). All responses were partial responses, and 50% of patients had stable disease. Notably, 1 patient had progressive disease. The disease control rate was 98% (95% CI, 86.8%-99.9%), and the clinical benefit rate was 75% (95% CI, 58.8%-87.3%).

Conversely, the combination generated no responses in patients in cohort 2 with chromophobe RCC (n = 7). Five patients had stable disease, 1 patient had progressive disease, and 1 patient was not evaluable. The disease control rate was 71% (95% CI, 29.0%-96.3%), and the clinical benefit rate was 29% (95% CI, 3.7%-71.0%).

“Our trial separated the diverse histologies into 2 cohorts and demonstrated differing efficacy results. Cohort 1 [predominantly papillary] met its primary end point with promising efficacy and was subsequently expanded, whereas cohort 2 [chromophobe] closed to accrual early for lack of objective responses and slow accrual,” lead study author Chung-Han Lee, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center, and colleagues, wrote.

RCC accounts for 90% of kidney cancer cases, with approximately 30% classified as non–clear cell RCC, including papillary, collecting duct, translocation-associated, chromophobe, and unclassified RCC. The current treatment landscape for non–clear cell RCC is sparse and not well defined.

Prior research has pointed to the activity of checkpoint inhibitors. For example, single-agent nivolumab elicited ORRs of 14% in patients with non–clear cell RCC in both the phase 4 CheckMate 374 trial (NCT02596035) and in cohort B of the phase 2 HCRN GU16-260 trial (NCT03117309).

Additionally, cabozantinib, a TKI that targets AXL, VEGFR2, and MET, demonstrated an improved ORR vs sunitinib (Sutent) in patients with papillary RCC. In January 2021, the FDA approved the combination of nivolumab and cabozantinib for the frontline treatment of patients with advanced RCC. However, the efficacy of the combination in non–clear cell RCC was unknown, and this single-center, phase 2 trial studied the efficacy of cabozantinib plus nivolumab in metastatic or advanced non–clear cell RCC.

The trial enrolled patients 18 years of age or older with pathologic or histologically confirmed, unresectable advanced or metastatic non–clear cell RCC into 2 cohorts. Cohort 1 was composed of patients with papillary, unclassified, translocation-associated, and fumarate hydratase (FH)–deficient RCC. Cohort 2 was composed of patients with chromophobe RCC.

Additional eligibility criteria stipulated that patients needed to have measurable disease per RECIST v1.1. criteria, no more than 1 prior systemic therapy, a Karnofsky performance status of at least 70%, and adequate organ function.

Patients were excluded if they had received prior immunotherapy or prior treatment with cabozantinib, or if they had untreated brain metastases.

All patients received concurrent therapy with 40 mg of oral cabozantinib once a day and 240 mg of intravenous (IV) nivolumab once every 2 weeks. This protocol was later updated to reflect the FDA-approved option of 480 mg of IV nivolumab once every 4 weeks until disease progression, intolerable toxicity, or withdrawal of patient consent. Patients also had protocol-guided options for cabozantinib dose reduction and dose re-escalation throughout treatment. To help prevent hand-foot syndrome associated with cabozantinib therapy, all patients applied clobetasol topically to their hands and feet twice per day for the first 12 weeks of therapy. Additionally, topical steroids could be continued beyond 12 weeks per investigator discretion.

During treatment, serial peripheral blood samples and archival tumor tissue were collected from each patient to develop biomarkers that correlated with treatment response.

The primary end point was ORR, defined as the percentage of patients who had complete or partial response. Secondary end points included progression-free survival (PFS), overall survival (OS), ORR by immune-related RECIST criteria, and assessment of treatment-related adverse effects (TRAEs).

A total of 47 patients were enrolled in the trial between August 28, 2018, and October 20, 2020. Cohort 1 was composed of 40 patients: 32 with papillary RCC, 6 with unclassified RCC, and 2 with translocation-associated RCC. Cohort 2 was composed of 7 patients with chromophobe RCC. The median ages were 57 years (range, 33-78) and 54 years (range, 46-68) in cohorts 1 and 2, respectively. Notably, 70% of patients in cohort 1 were male compared with 43% in cohort 2. The median number of disease sites was 2 (range, 1-7) and 2 (range, 1-3) in cohorts 1 and 2, respectively.

Patients had a Karnofsky performance status of 90 (73% and 71% in cohorts 1 and 2, respectively) or 80 (27% and 29%); an International Metastatic RCC Database Consortium risk classification of favorable (20% and 43%), intermediate (67% and 43%), or poor (13% and 14%); prior nephrectomy (67% and 100%); prior systemic therapy with a VEGF inhibitor (25% and 29%), an mTOR inhibitor (20% and 0%), or chemotherapy (5% and 0%); and metastases located in the lymph node (78% and 29%), lung (45% and 29%), bone (30% and 29%), retroperitoneum/peritoneum (25% and 57%), or liver (20% and 29%).

Additional data showed cabozantinib and nivolumab elicited an ORR of 47% (95% CI, 29%-65%). in patients with papillary RCC. Three patients with unclassified RCC had an objective response, as well as 1 patient with translocation-associated RCC. All 5 patients with FH-deficient RCC achieved an objective response.

In cohort 1, the median PFS was 12.5 months (95% CI, 6.3-15.9), and the estimated 12-month PFS rate was 52.8% (95% CI, 34.1%-68.5%). The median duration of response was 13.6 months (95% CI, 9.7-19.8). The median OS was 28 months (95% CI, 16.3­–not evaluable), with an estimated 18-month OS rate of 68.7% (95% CI, 46.3%-83.3%). Notably, of 19 patients who achieved an objective response, 10 experienced subsequent disease progression, and 9 remained on treatment with a continued response at the time of data cutoff.

In cohort 2, the median PFS was not calculated because of the small cohort size. Of the 2 patients with a PFS greater than 24 weeks, 1 remained on treatment with stable disease, and the other withdrew from study protocol to undergo ablation.

Correlative analysis through targeted exome sequencing by MSK-IMPACT was performed on 37 patients, including 32 in cohort 1 and 5 in cohort 2. The most common alterations in cohort 1 were 

 (16%). The most common alterations in cohort 2 were 

 mutations are frequent in non–clear cell RCC and could be associated with differential treatment responses, as 10 of 12 patients with 

 mutations achieved an objective response compared with 1 of 6 patients with 

“Genomic studies highlight the heterogeneity of non–clear cell RCC and warrant further study as predictors of response to systemic therapy,” the study authors wrote.

In terms of safety, 87% (n = 41) of patients experienced TRAEs of any grade, with 32% (n = 15) of patients experiencing grade 3 or 4 TRAEs. No grade 5 TRAEs were seen. The most common grade 3 or 4 TRAEs included hypertension (13%), diarrhea (6%), and palmar-plantar erythrodysesthesia syndrome (4%).

Common TRAEs of any grade included fatigue (57%), palmar-plantar erythrodysesthesia syndrome (57%), diarrhea (53%), hypertension (38%), dry mouth (36%), nausea (30%), oral mucositis (28%), hoarseness (26%), constipation (21%), dry skin (21%), dyspnea (21%), and headache (21%).

Aggregate treatment exposure and tolerance were analyzed in all 47 patients. At the time of data cutoff, the median duration of treatment was 11.0 months (95% CI, 7.8-21.1), with 20 patients remaining on treatment with at least 1 therapy. A total of 27 patients discontinued cabozantinib, and 28 discontinued nivolumab. Of these patients, 20 discontinued treatment because of progressive disease, and 10 stopped receiving 1 or both therapies because of TRAEs.

The median duration of treatment for cabozantinib was 9.1 months (95% CI, 7.4-21.1). A total of 79% (n = 37) of patients reduced cabozantinib dosage, and 13% (n = 6) discontinued cabozantinib treatment because of AEs, including palmar-plantar erythrodysesthesia, which was seen in 2 patients.

The median duration of treatment for nivolumab was 10.6 months (95% CI, 6.0-18.8). A total of 17% (n = 8) of patients required high-dose steroids, and 17% discontinued nivolumab treatment because of AEs, including grade 3 hepatitis, which was reported 3 patients.

Lee CH, Voss MH, Carlo MI, et al. Phase II trial of cabozantinib plus nivolumab in patients with non–clear-cell renal cell carcinoma and genomic correlates. 

. Published online March 17, 2022. doi:10.1200/JCO.21.01944

Vogelzang NJ, Olsen MR, McFarlane JJ, et al. Safety and efficacy of nivolumab in patients with advanced non-clear cell renal cell carcinoma: results from the phase IIIb/IV CheckMate 374 study. 

. 2020;18(6):461-468.e3. doi:10.1016/j.clgc.2020.05.006

Atkins MB, Jegede O, Haas NB, et al. Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced non-clear cell renal cell carcinoma (nccRCC) (HCRN GU16-260-Cohort B). 

 2021;39(suppl 15):4510. doi:10.1200/JCO.2021.39.15_suppl.4510

Phase 2 trial findings indicate that cabozantinib plus nivolumab may be effective in treating patients with non-clear cell renal cell carcinoma with papillary histology.

Cabozantinib/Nivolumab Showcases Clinical Benefit in Papillary Non–Clear Cell RCC 

Not only did ARO-HIF2, an investigational RNA interference (RNAi) therapy, reduce levels of hypoxia inducible factor-2 alpha (HIF2α) expression in patients with clear cell renal cell carcinoma (RCC), the agent was also found to have a manageable safety profile, according to data from the phase 1b AROHIF21001 trial (NCT04169711).

Findings from the trial, which were presented during the 2022 Genitourinary Cancers Symposium, showed that of 26 evaluable patients, 9 experienced a median reduction in HIF2α mRNA of 30% (range, -19% to -59%) by qPCR.

In the subset of patients who received ARO-HIF2 at 225 mg (n = 7) the median reduction in HIF2α mRNA was 46% (range, -22 to -47). In those who were administered 525 mg of ARO-HIF2 (n = 10), the median reduction in HIF2α mRNA was 27% (range, -19 to -39). In the subset of patients who were given 1050 mg of the agent (n = 9), the median reduction in HIF2α mRNA was 44% (range, -28 to -49).

Additionally, 14 patients achieved a median reduction in HIF2α protein of 26% (range, -1700 to -98) by immunohistochemistry (IHC). The HIF2α protein reduction rates in the 225-mg, 525-mg, and 1050-mg cohorts were 26% (range, -26 to -82), 47% (range, 0 to -90), and 0% (range, 1700 to -98), respectively.

“This ongoing phase 1 study provides initial proof of target engagement based on reductions in HIF2α expression, as well as an acceptable safety profile in response to escalating doses of ARO-HIF2,” lead study author James Brugarolas, MD, PhD, of UT Southwestern Medical Center, and colleagues, wrote in a poster on the findings.

HIF2α is usually expressed at low levels and targeted for degradation by the von Hippel-Lindau (VHL) tumor suppressor protein. However, VHL inactivation, which is a causative event of clear cell RCC, prompts tumorigenesis through uncontrolled HIF2α accumulation. The synthetic double-stranded RNAi trigger, ARO-HIF2, which includes an alpha-v beta3 targeting ligand, was developed to silence HIF2α expression.

The AROHIF21001 trial enrolled patients with advanced or metastatic clear cell RCC that progressed during or after at least 2 prior regimens which must have included a VEGF-targeted therapy and a checkpoint inhibitor therapy.

 To be eligible for participants, patients needed to be at least 18 years of age, have an ECOG performance status of 0 or 1, a life expectancy that was longer than 3 months, and organ function that was considered to be acceptable at the time of the screening.

Exclusion criteria included a history of untreated brain metastases, having received prior systematic therapy or radiation therapy within 2 weeks of the first dose of study treatment, or having previously undergone solid organ or stem cell transplantation. Moreover, patients could not be receiving current treatment with immune checkpoint inhibitors, nor could they have received prior HIF2 inhibitors within 6 months before their first dose of study treatment.

Intravenous ARO-HIF2 was administered weekly at 225 mg in cohort 1 (n = 7), 525 mg in cohort 2 (n = 10), and 1050 mg in cohort 3 (n = 9). Moreover, tumor growth was evaluated by biopsy at baseline and again at 2 weeks. Additionally, patients were evaluated for safety each week. Every 8 weeks, participants were examined for tumor response by RECIST criteria.

The primary end point of the study was to evaluate treatment-emergent adverse effects (TEAEs) associated with ARO-HIF2. Secondary end points included pharmacokinetics and preliminary efficacy per RECIST v1.1 criteria.

Exploratory end points included the assessment of post-dose tumoral expression of HIF genes in response to treatment with the agent, change in tumor integrin expression, correlation of integrin expression with changes in HIF gene expression, and the examination of serum biomarkers of agent activity. The correlation of disease-related gene expression to the activity of the agent is also under exploration. Plasma and urine metabolites will also be assessed.

Spanning cohorts, the mean age was 65.1 years (range, 44-87). Seventy-seven percent of patients were male. Regarding performance status, 42.3% of patients had an ECOG performance status of 0, and 57.7% had a status of 1. Most patients (53.8%) had intermediate-risk disease per International Metastatic RCC Database Consortium criteria; 23.1% had good-risk disease and 15.4% had poor-risk disease.

Additionally, 30.8% of patients received 2 prior lines of therapy, 30.8% received 3 prior lines, and 11.5% received 4 prior lines of therapy. Notably, 26,9% of patients received 5 or more prior lines of treatment. Prior treatment included anti-VEGF therapy (100%) and checkpoint inhibition (100%). Regarding 

 mutation status, 17.6% of patients had frame shift mutations, 29.4% had missense mutations, 5.9% had in frame deletion, 11.8% had no variant, and 35.3% did not have this information available.

Prior data from the trial showcased early signals of activity with ARO-HIF2 in the 225 mg and 525 mg cohorts.

 Specifically, 7 of 9 patients who had evaluable tumor samples and received treatment experienced reductions in HIF2α per IHC H-score. Notably, these reductions ranged from -9% to -82%, with a mean reduction of -48%.

Additional data presented during the 2022 Genitourinary Cancers Symposium showed that ARO-HIF2 elicited an objective response rate of 7.7% in all patients, with 2 patients experiencing a partial response. Furthermore, 30.8% of patients achieved stable disease and 50.0% experienced disease progression. One patient was not evaluable for response, and response data were missing for 2 patients. Overall, the disease control rate with the agent was 38.5%.

At least 1 TEAE of any grade occurred in 96.2% of patients. Specifically, 57.7% of patients experienced at least 1 grade 1 or 2 TEAE, 30.8% reported at grade 3 TEAE, 3.8% experienced a grade 4 TEAE, and 3.8% experienced a grade 5 TEAE. Serious TEAEs were reported in 34.6% of patients. Moreover, treatment-related AEs of any grade occurred in 65.4% of patients. One patient discontinued treatment due to TEAEs.

TEAEs of any grade that occurred in more than 4 patients included fatigue (50.0%), dizziness (26.9%), dyspnea (26.9%), nausea (23.1%), abdominal pain (23.1%), neuropathy (19.2%), and constipation (19.2%).

Enrollment for the phase 1 trial remains open and enrollment is ongoing.

Brugarolas J, Beckermann KE, Rini BI, et al. Initial results from the phase 1 study of ARO-HIF2 to silence HIF2-alpha in patients with advanced ccRCC (AROHIF21001). 

 2022;40(suppl 6):339. doi:10.1200/JCO.2022.40.6_suppl.339

Study of ARO-HIF2 in patients with advanced clear cell renal cell carcinoma. ClinicalTrials.gov. Updated April 19, 2021. Accessed May 3, 2022. 

https://clinicaltrials.gov/ct2/show/NCT04169711

Arrowhead announces positive interim results from phase 1b study of ARO-HIF2 for treatment of clear cell renal cell carcinoma. News release. Arrowhead Pharmaceuticals, Inc. July 6, 2021. Accessed May 3, 2022. 

This article was originally published on OncLive as “ARO-HIF2 Lowers HIF2α Expression and Demonstrates Favorable Safety Profile in Clear Cell RCC”

Patients with clear cell renal cell carcinoma experienced reduced levels of hypoxia inducible factor-2 alpha expression following treatment with ARO-HIF2. 

Investigational RNA Interference Therapy, ARO-HIF2, Yields Encouraging Phase 1 Results in Clear Cell RCC

Conversations surrounding fertility preservation may differ between young men and women with cancer, according to Donna Herrera Bell, MSN, APRN, FNP-C.

How To Approach Fertility Conversations With AYA Patients as an Oncology Nurse

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Kate Sandstrom on Ensuring Patient Follow-Up With Radiation Oncology Teams

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Cancer Survivors Struggling With Insomnia May Benefit from Cognitive Therapy 

Oncology nurses may be able decrease peripheral access wait times for patients, however, a change in culture may be necessary to see full results.

Patient Wait Times Reduced by Teaching Oncology Nurses to Insert Ultrasound-Guided Peripheral IV 

Jessica MacIntyre, ARNP, NP-C, AOCNP, discusses empowering oncology nurse navigators to refer patients undergoing chemotherapy or radiation therapy to nutrition services. 

Jessica MacIntyre on Utilizing Nurse Navigators to Connect Patients to Nutrition Services

Gina Mauro currently serves as Vice President of Content at MJH Life Sciences, overseeing 

®. Gina joined the company in 2015 and has held various positions on 

Prior to joining MJH Life Sciences, she worked at Gannett as a full-time reporter with the Asbury Park Press. Email: gmauro@onclive.com

Niraparib improved or maintained health-related quality of life, pain intensity, and pain interference in patients with advanced or metastatic castration-resistant prostate cancer.

Niraparib Showcases Improved Health-Related QOL, Reduced Pain Burden in mCRPC

Single nucleotide polymorphism (SNP) genotyping could be used to predict radiation dermatitis in patients with breast cancer.

Single Nucleotide Polymorphism Genotyping Could Predict Severe Radiation Dermatitis in Breast Cancer 

Kristi Rosa joined MJH Life Sciences in 2016 and has since held several positions within the company. Prior to working at the company, she served as lead copywriter and marketing coordinator at The Strand Theater. Email: krosa@onclive.com

Fam-trastuzumab deruxtecan-nxki is now an FDA-approved regimen for the treatment of patients with unresectable or metastatic HER2-positive breast cancer.

FDA Approves Trastuzumab Deruxtecan for Unresectable or Metastatic HER2+ Breast Cancer

Increasing the number of intravenous port nurse champions across a health care system helps to keep oncology nurses with their patients and reduce care delays. 

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