For a downloadable version that you can print at home, check out our 

» As maintenance therapy for patients with recurrent ovarian epithelial, fallopian tube, and primary peritoneal cancer who have a complete or partial response (CR/PR) to platinum-based chemotherapy regardless of 

» As maintenance therapy for patients with deleterious or suspected deleterious germline or somatic 

-mutated advanced ovarian epithelial, fallopian tube, and primary peritoneal cancer who have a complete or partial response to frontline platinum-based chemotherapy. 

» In combination with bevacizumab (Avastin) maintenance treatment of patients with advanced ovarian cancer who have a CR/PR to first-line platinum-based chemotherapy with bevacizumab and whose cancer is associated with homologous recombination deficiency (HRD). Positive HRD status is defined by either a deleterious or suspected deleterious 

» Patients with germline BRCA-positive, HER2-negative metastatic breast cancer who have previously received chemotherapy. Patients with hormone receptor-positive disease must also have had prior endocrine therapy. 

-mutated, HER2-negative, highrisk early breast cancer who have undergone chemotherapy before or after surgery. Patients with hormone receptorpositive disease must also have had prior endocrine therapy. 

-mutated metastatic pancreatic adenocarcinoma whose disease has not progressed after at least 16 weeks of a first-line platinum-based chemotherapy regimen. 

» Patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) genemutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga).

Olaparib has been studied in several phase 2 and 3 trials across various malignancies. 

In the phase 3 SOLO-1 trial (NCT01844986), patients with 

 mutation–positive advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer achieved a 70% reduction in risk of disease progression or death in patients with frontline maintenance olaparib than with placebo. In the phase 3 SOLO-2 trial (NCT01874353), maintenance treatment with olaparib yielded a 70% reduction in the risk of progression or death compared with placebo for patients with platinumsensitive, relapsed, 

-mutant ovarian cancer. The phase 3 PAOLA-1 trial (NCT02477644) revealed that the combination of olaparib and bevacizumab led to a 41% reduction in the risk of disease progression or death compared with bevacizumab alone in patients with HRD-positive advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who have CR/PR to platinum-based chemotherapy plus bevacizumab (HR, 0.59; 95% CI, 0.49-0.72;

 < .001). After a median follow-up of 22.9 months, the median PFS was 22.1 vs 16.6 months, respectively. In the subgroup of patients with 

 gene mutation–positive cancers, the PFS benefit was even more profound (HR, 0.31; 95% CI, 0.20-0.47). 

-positive, HER2-negative metastatic breast cancer, patients who received olaparib monotherapy experienced a 42% improvement in invasive disease-free survival in the phase 3 OlympiAD trial (NCT02000622) compared with standard therapy (HR, 0.58; 95% CI, 0.46- 0.74; 

 < .0001). In March 2022, findings from the phase 3 OlympiA (NCT02032823) trial found that olaparib reduced the risk of death by 32% compared with placebo (HR, 0.68; 98.5% CI, 0.47-0.97; 

= .009) in BRCA-mutated, HER2-negative, high-risk early breast cancer. Furthermore, the 3-year survival rate was 92.8% with the PARP inhibitor compared with 89.1% for placebo. 

In the phase 3 POLO trial (NCT02184195), patients with germline 

-mutated metastatic pancreatic cancer achieved a median progression-free survival (PFS) of 7.4 months with olaparib compared with 3.8 months on placebo (HR, 0.53; 95% CI, 0.35-0.81; 

= .0035). Moreover, after 2 years, 22.1% of patients in the olaparib group had no disease progression vs 9.6% in the placebo group.

Findings from the phase 3 PROfound trial (NCT02987543) showed that olaparib induced a 66% reduction in the risk of disease progression or death compared with abiraterone acetate or enzalutamide (HR, 0.34; 95% CI, 0.25-0.47; 

PARP enzymes are involved in DNA repair and are specifically responsible. Olaparib is a potent oral PARP inhibitor which induces synthetic lethality in 

 deficient tumor cells through the formation of double-stranded DNA breaks which cannot be accurately repaired, leading to cell death. 

Olaparib is an oral drug manufactured in 150-mg and 100-mg tablets. Olaparib is taken by mouth, twice daily. It can be taken without or without food. Olaparib should be taken as prescribed, and capsules should be swallowed whole. Do not crush, dissolve, or open capsules. 

The recommended dosing for metastatic breast cancer is 300 mg by mouth every 12 hours. 

The most common types of adverse events (AEs) associated with olaparib are hematologic and gastrointestinal (GI). Anemia is the most common hematologic toxicity and occurs in up to 45% of patients. Neutropenia and thrombocytopenia are less common. A dose reduction should be considered for recurrent anemia (hemoglobin < 8 mg/dL) and/or to avoid multiple blood transfusions. Olaparib is considered moderately emetogenic, and 5-HT3 receptor antagonists (eg, ondansetron) are recommended as prophylaxis. Consider reducing dose for persistent nausea requiring daily antiemetics and/or resulting in greater than 5% weight loss. Rare but serious AEs include secondary myelodysplastic syndrome/acute myeloid leukemia (< 2%) and pneumonitis. If prolonged hematologic toxicity is observed (≥ grade 2 or > 4 weeks), further evaluation is warranted. Interrupt treatment and evaluate promptly for new or worsening respiratory symptoms (eg, cough, dyspnea, wheezing) or radiographic abnormalities. Olaparib should be permanently discontinued if pneumonitis is confirmed. The dose should be continued until disease progression unless there is toxicity, in which case it can be reduced to 200 mg every 12 hours or 100 mg every 12 hours. A dose adjustment is recommended for a creatinine clearance (CrCl) of 31 to 50 mL/min. The medication has not been studied in patients with CrCl below 30 mL/min or end-stage renal disease. No adjustment is needed for hepatic impairment. 

Patients about to begin treatment with olaparib should be advised to avoid grapefruit juice and Seville oranges as both may increase the level of olaparib in the blood. 

ADVICE FOR NURSES WHO ADMINISTER THIS AGENT 

Prior to initiating olaparib, health care professionals should rule out pregnancy, kidney dysfunction, and lung and breathing problems. Safety and monitoring parameters include obtaining a pregnancy test at baseline in female patients, complete blood count with differential at baseline and monthly thereafter, and ongoing monitoring for signs and symptoms of thromboembolism. 

Olaparib should be stored in its original container and in a cool and dry environment to protect it from moisture. 

In August 2022, AstraZeneca voluntarily withdrew the indication for the treatment of adult patients with deleterious or suspected germline 

-mutant advanced ovarian cancer who have been treated with 3 or more lines of chemotherapy. New treatment of patients who meet these criteria should not be initiated and patients who are receiving olaparib in this setting should consult their physician to make an informed decision on their ongoing care.

1. Lynparza. Prescribing information. AstraZeneca Pharmaceuticals LP, 2022. Accessed August 15, 2022. bit.ly/3AfVZyC 

2. Important prescribing information: Lynparza. AstraZeneca. August 26, 2022. Accessed September 29, 2022. https://bit.ly/3C4k4ud

Articles

Olaparib is an oral drug manufactured in 150-mg and 100-mg tablets. Olaparib is taken by mouth, twice daily. It can be taken without or without food.

Oncology Drug Crash Course: Olaparib (Lynparza)

Favorable objective responses were observed among patients with 

 fusion–positive solid tumors who received selpercatinib (Retevmo), according to an interim analysis of the ongoing phase 1/2 LIBRETTO-001 trial (NCT03157128). The positive clinical responses observed in these patients underscores the importance of comprehensive genomic testing in this setting, the study authors noted.

At a prespecified interim analysis, the objective response rate (ORR) associated with selpercatinib was 43.9% (95% CI, 28.5%-60.3%; n = 18/41). The most frequently reported treatment-emergent adverse events (TRAEs) included hypertension (22%), increased alanine aminotransferase (16%), and increased aspartate aminotransferase (13%). Serious TRAEs were reported in 40% of patients, but no treatment-related deaths occurred.

“The activity of selpercatinib in a broad variety of 

 fusion–positive solid tumors is clinically meaningful, providing durable responses in patients previously treated with standard-of-care therapies, or for whom no standard of care exists,” wrote Vivek Subbiah, MD, associate professor in the Department of Investigational Cancer Therapeutics and Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, and coinvestigators in a recent paper published in 

. “These findings emphasize the importance of broad-based genomic profiling to identify patients with 

 fusions who might benefit from selpercatinib treatment.”

Selpercatinib is a RET kinase inhibitor which has demonstrated intracranial nervous system activity. It has also demonstrated preclinical activity in 

 fusion–positive lung and thyroid cancers.

Based on initial findings from the LIBRETTO-001 trial, the FDA granted selpercatinib 

 to treat patients with solid tumor harboring a 

 gene fusion mutation. This open-label, basket trial of selpercatinib enrolled patients aged 18 years or older who had an ECOG performance status of 0 to 2. Patients received oral selpercatinib in a continuous 28-day cycle. In the phase 1 dose-escalation study, patients received 20 mg once daily or 20-240 mg twice daily. In the phase 2 setting, patients received 160 mg twice daily.

A total of 806 patients were enrolled into LIBRETTO-001, of whom 45 tested positive for a 

fusion. In this specific cohort, 58% (n = 26) had refractory gastrointestinal malignancies, other diagnoses in this cohort included salivary, breast, sarcoma, xanthogranuloma, carcinoid, ovarian, pulmonary carcinosarcoma, and carcinoma of the skin. All patients with 

fusion–positive disease had received a median of 2 prior systemic therapies. Fourteen of these patients had been pretreated with at least 3 prior therapies.

Almost all patients (96%) initiated treatment at the recommended selpercatinib dose of 160 mg twice daily. One of the 2 patients who started on a reduced dose successfully escalated their treatment up to a 160 mg twice daily dose. The other patient continued with their reduced dose of 120 mg twice daily throughout treatment.

In addition to favorable ORR and safety data, this analysis provided updates on clinical benefit outcomes, duration of response, time to response, progression-free survival (PFS), and overall survival (OS).

A complete response was reached in 2 patients (5%) and the clinical benefit (defined as the proportion of patients with a best overall response of complete response, partial response, or stable disease lasting ≥ 16 weeks) was 63.4% (95% CI, 46.9%-77.9%; n = 26/41).

The median duration of response was 24.5 months (95% CI, 9.2-not evaluable [NE]) according to independent review committee and 18.4 months (9.2-NE) according to investigators. Moreover, the median time to best response was 1.9 months, according to both the independent review committee and the investigators.

According to the independent review committee, the median PFS with selpercatinib was 13.2 months (95% CI, 7.4-26.2), with a 1-year PFS rate of 53.1% (95% CI, 34.1%-68.8%), and a 2-year PFS rate of 32.1% (95% CI, 14.0%-51.7%). Median OS was 18.0 months (95% CI, 10.7-NE) and at 18 months the estimated OS rate was 51.7% (95% CI, 32.9%-67.6%).

The safety profile was reported to be consistent with previous findings; a total of 3 patient developed grade 5 TEAEs (7%). The most common serious TREAEs included abdominal pain, nausea, pyrexia, and vomiting.Patients also experienced drug-induced liver injury, fatigue, and hypersensitivity because of treatment.

 alterations are clinically validated actionable oncogenic drivers in lung and thyroid cancers, and selpercatinib has been shown to be beneficial for patients with these diseases,” study authors concluded. “This study shows that 

 fusions are oncogenic drivers in other cancers and that selpercatinib is a potentially effective treatment for 

 fusion–positive cancers regardless of tumor type.”

Subbiah V, Wolf J, Konda B, et al. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. 

. 2022;23(10):1261-1273. doi:10.1016/S1470-2045(22)00541-1

Selpercatinib demonstrated a promising efficacy profile in patients with RET-fusion positive solid tumors. 

Promising Selpercatinib Data Highlight Value of RET Fusion Testing for Patients With Solid Tumors

Over the past few decades, the number of advanced practice providers (APPs) in oncology has increased dramatically and the role they play expanded greatly. One reason for this is that there are more patients who need oncologists in the US than there are physicians practicing the specialty. According to the American Society of Clinical Oncology, the nation will see a shortage of more than 2200 oncologists by 2025 and an increase of 40% in demand for cancer treatment during the next 6 years.

 This growth in demand is driven not only by new patients, but by those who have completed active treatment and require follow-up care. Thanks to advanced therapies, better outcomes are being achieved and survival rates are improving. Cancer survivors—even with complex comorbidities—are living longer than ever before.

Survivorship care can readily be performed by APPs, given their wide breadth of expertise and training. A closer look at how these highly skilled professionals deliver survivorship care will provide some insight into why they areideally suited to lead these programs, meeting a critical need that will only grow in the future.

In many practices, APPs are the backbone of survivorship programs, playing a key role in their planning and execution. They are well suited to lead these programs because of their extensive education, training, and scope of practice.

They also develop strong relationships with patients and caregivers during active treatment. As trusted members of the care team, it makes sense for them to discuss the key elements of survivorship with patients, some of which—like lifestyle changes and advance care planning—can be difficult to talk about.

Many patients are under the misconception that survivorship doesn’t begin until they have finished active treatment. According to the National Cancer Institute, however, a patient is considered to be a survivor from the time of diagnosis until the end of life.

APPs can help patients understand that survivorship encompasses everything from diagnosis onward—be they undergoing treatment, in remission, or facing recurrence.

A Critical Role at All Stages of Survivorship

APPs make valuable contributions at all stages of the survivorship journey.

They manage patients during active treatment, helping them keep side effects under control so that they can adhere to treatment. They educate patients about what to look for so that side effects can be caught early and dealt with more easily. They support the psychological well-being of patients by addressing their expectations and fears. They talk with patients early on about the emotional impact of the diagnosis, teach them stress-coping skills, and refer them to mental health professionals if and when necessary.

Once active treatment ends, the focus shifts to long-term surveillance. Patients may not be cured but they may be in remission, so ongoing follow-up care is critical, from a clinical and psychological standpoint.

By this stage, a long-term care plan has been developed that spells out exactly what treatment has been given and what follow-up care is needed and when. It details intervals between office visits and the imaging, lab tests, and other surveillance that may be needed. It also includes information that helps patients and their care team recognize signs of recurrence, the emergence of a secondary cancer, and potential long-term side effects like cardiotoxicity.

The transition away from active treatment is always stressful for patients because they must adjust to many changes, including less frequent office visits, which may make them feel as if they lack support. APPs play an important role at this stage, as by now they have a good relationship with patients and their caregivers. They can thus communicate effectively about such sensitive topics as patient emotions, lifestyle changes, and advance care planning. APPs are able to recognize signs of distress during this transition and provide appropriate assistance, whether that be by getting patients into support groups, referring them to mental health professionals, or prescribing medication.

Once active treatment concludes, patients may transition to receiving most of their care from a primary care physician. A detailed survivorship plan makes the PCP intimately familiar with a patient’s condition and needs. And APPs are always available to offer advice about mutual patients.

There is always a concern that the patient may not adhere to a survivorship plan. Because they interact less frequently with the oncology care team, they may lose motivation. APPs must make sure patients understand not only the plan but the need for them to become more responsible for their own health.

This is also a time when APPs are very vigilant about checking for anxiety and depression so that they can catch the conditions before they get out of control. Primary care providers can also be brought into the discussion and intervene if need be.

A survivorship plan is key to providing high-quality, patient-centered care. It must be developed early on to ensure the best patient experience and quality of life. APPs are ideally situated to manage or lead cancer survivorship because of the close relationship they establish with patients and their caregivers. Practices also benefit from such work because it allows physicians to focus on other priorities. Integrating APPs into survivorship care is a trend that will only grow in the future owing to the tremendous benefits it offers to the practice and its patients.

Finnegan J. Another physician shortage: oncologists.Fierce Healthcare

https://www.fiercehealthcare.com/practices/another-physician-shortage-oncologists

Survivor. NCI Dictionary of Cancer Terms. National Cancer Institute. Accessed July 13, 2022. 

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/survivor

Advanced practice providers are the future of survivorship care because of the tremendous value they offer to the practice and its patients. 

Advanced Practice Providers Are Uniquely Suited for Survivorship Care

Long-term findings from the phase 3 TIVO-3 trial (NCT02627963) showed that tivozanib (Fotdiva) inspired superior overall survival (OS) in patients with relapsed/refractory advanced renal cell carcinoma (RCC) compared with sorafenib (Nexavar). Moreover, according to presenters at the 2022 Kidney Cancer Research Summit, the benefit was particularly profound among those who remained progression-free at a 1-year follow-up.

At 2 years following the last-patient-in, the mean follow-up was 17.9 months (95% CI, 16.7-19.1), and 65% (n = 227) of patients had experienced an OS event. At that time, the OS hazard ratio (HR) was 0.99 (95% CI, 0.76-1.29). With mean follow-up extended to 22.8 months (95% CI, 20.9-24.6), 80% (n = 280) of patients had experienced an OS event, and the OS HR lowered to 0.89 (95% CI, 0.70-1.14; 

 = .3533). Here, the median OS was 16.4 months (95% CI, 13.4-21.9) with tivozanib vs 19.1 months (95% CI, 14.9-24.2) with sorafenib.

“Long-term follow-up in TIVO-3 suggests that early and consistent PFS [progression-free survival] benefit with tivozanib over sorafenib may be associated with an improvement in OS HR over time as more events accumulate,” lead study author Brian I. Rini, MD, professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee, and coauthors, wrote in the poster.

Tivozanib is an oral VEGF inhibitor approved by the FDA for the treatment of patients with relapsed/refractory RCC following at least 2 prior therapies.

The approval was based on prior findings from TIVO-3, which demonstrated a significant improvement in PFS with tivozanib vs sorafenib (HR, 0.73; 95% CI, 0.56-0.93). Additional findings showed that the 3-year PFS rate favored tivozanib vs sorafenib, at 12% vs 2%, respectively.

The study enrolled 350 patients who had progressed on 2 or 3 prior systemic treatments, including at least 1 VEGFR TKI. Patients were randomly assigned 1:1 to 1.34 mg of oral tivozanib daily for 3 weeks on, 1 week off, or 400 mg of oral sorafenib twice daily every 4 weeks until progression or unacceptable toxicity.

To better gauge survival data, investigators evaluated the effects of event accumulation and data maturation on the stability of Kaplan-Meier survival estimates over time with extended follow-up.

“Serial OS analyses using Kaplan-Meier estimates are affected by increased curve reliability with decreased censoring and limited residual patients at risk for death,” the study authors wrote.

Notably, when OS was conditioned on clinically relevant landmark PFS time points, a statistically significant improvement in OS was seen in patients who received tivozanib vs sorafenib (12-month PFS: HR, 0.45; 95% CI, 0.22-0.91; 

 = .0221; 18-month PFS: HR, 0.46; 95% CI, 0.15-1.39; 

When conditioned on PFS of at least 12 months, the median OS was 48.3 months (95% CI, 32.8–not reached [NR]) with tivozanib vs 32.8 months (95% CI, 27.6-50.0) with sorafenib. When conditioned on PFS of at least 18 months, the median OS was 54.3 months (95% CI, 44.9-NR) and 50.0 months (95% CI, 32.4-NR) with tivozanib and sorafenib, respectively.

Rini BI, Pal SK, Escudier B, et al. Maturation of overall survival in TIVO-3 with long-term follow-up. Presented at: Kidney Cancer Research Summit; October 6-7, 2022; Philadelphia, PA. Abstract 75. Accessed October 10, 2022. 

Tivozanib, an oral VEGF inhibitor, improved overall survival in patients with relapsed or refractory, advanced renal cell carcinoma. 

Tivozanib Outperforms Sorafenib in Extending Overall Survival in Advanced RCC

According to the American Association of Nurse Practitioners, over 36,000 new nurse practitioners (NPs) completed academic programs between 2019 and 2020, and licensed NPs reportedly increased from 325,000 in 2021 to 355,000 in 2022.

As the number of new graduates continues to rise, so will the need for preceptorship, especially in specialties such as oncology.

Preceptors help novices navigate their new role as health care providers, coaching them on such core competencies as diagnostic reasoning, clinical judgment, and critical thinking skills.

 The transition from student to NP can be very difficult, and thus the importance of highly experienced preceptors, particularly in oncology, cannot be overemphasized.

To provide care to oncology patients, NPs need highly specialized training and education, which they usually receive during postgraduate fellowships.

The preceptors’ primary goal is to help the novice bridge educational gaps and advance from entry-level competence to high-level proficiency.

They share knowledge and clinical skills, facilitate experiential learning scenarios, and encourage the development of social, critical thinking, and clinical judgment skills. Preceptors provide this for the novice NP while simultaneously providing safe, high-quality, and holistic care to patients.

Although preceptors are considered to be experts, they still need guidance themselves. According to Pleshkan et al,

 a structured preceptorship improves the process of training a novice NP. Preceptors share their knowledge with the NPs and teach them effective ways to analyze their clinical decisions and manage their workload.

Preceptors must employ the teaching strategies that are best suited to each learner’s style

 and assess the preceptees’ depth of knowledge and level of clinical expertise to facilitate a positive experience.

 In addition, an open dialogue between preceptor and novice gives both the opportunity to become acquainted with one another, clarify goals and expectations, and give/receive constructive feedback. Open dialogue has also been shown to be an effective way to build the preceptor-preceptee relationship and create mutual respect and trust as well as a positive learning environment.

Emotional Support and the Preceptorship Experience

Transitioning from new graduate to proficient NP in any specialty takes time and determination as the process can be intimidating and, at times, anxiety-inducing.

 However, having a guide who has been through the same process can make the transition a healthy and pleasant experience.5 Preceptors ensure the competence of novices. From them novices learn to provide safe, cost-effective care to patients with complex diseases.

What may at first seem like a daunting journey becomes less so thanks to the preceptor’s ongoing reassurance. Preceptors are like personal coaches: they teach learners what to do and offer emotional support throughout.

As I transition from an experienced RN to a novice oncology NP, I see that preceptors have been a critical part of my personal and professional growth. Although most preceptorships are short and not all encounters are positive, many of the connections are genuine. Several of my past preceptors have become lifelong friends and continue to be mentors of mine. Because of their willingness to share their knowledge and clinical expertise, I am confident that when my turn comes, I will be able to pass on what they taught me (plus some tips and tricks of my own) to the next generation.

Novice oncology NPs require a great deal of support as they transition to their new role.

 A structured preceptorship that caters specifically to them promotes a safe environment that is conducive to learning, builds competence, confidence, and job satisfaction and encourages intra- and interdisciplinary collaboration.

 To novice oncology NPs starting their journey in clinical practice, I say that to succeed, you must pay attention, ask questions, and maintain a flexible and positive attitude.

1. NP fact sheet. American Association of Nurse Practitioners. Updated April 2022. Accessed July 15, 2022. https://www.aanp.org/about/all-about-nps/np-fact-sheet

2. Pleshkan V, Boykins AD. Cognitive preceptorship: an emerging nurse practitioner role transition to practice model. 

.2022;39:194-205. doi:10.1016/j.profnurs.2022.02.002

3. Pleshkan V, Hussey, L. Nurse practitioners’ experience with role transition: supporting the learning curve through preceptorship. 

4. Bazzell AF, Jones T, Dains JE, Champion JD. Assessing the needs of oncology APRN preceptors. 

5. Pirschel C. Competencies create expert, accountable nurses delivering quality care. 

.April 3, 2017. Accessed July 15, 2022. https://voice.ons.org/news-and-views/core-competencies-of-oncology-nurses

6. Alencar M, Butler E, MacIntyre J, Wempe EP. Nurse practitioner fellowship: developing a program to address gaps in practice. 

7. Pearson T, Hensley T. Positive precepting: identifying NP student learning levels and needs. 

8. Thomassen A. Fellowship programs: reflections of an advanced practice nurse fellow. 

9. Kelly DE. Initiation of a new nurse preceptor program in the era of COVID-19. 

10. Bazzell AF, Dains JE. Supporting nurse practitioner preceptor development. 

Structured preceptorships promote competence, confidence, and job satisfaction in new oncology nurse practitioners. 

Supporting the Novice Oncology NP: The Benefits of Preceptorship

Compared with chemotherapy or second-line androgen deprivation therapy (ADT), single-agent rucaparib significantly improved radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (CRPC) harboring 

 mutations, according to findings from the phase 3 TRITON3 trial (NCT02975934).

-mutated CRPC treated with rucaparib (n = 201) achieved a median rPFS of 11.2 months. For patients in the control group, rPFSwas 6.4 months (n = 101; HR, 0.50; 95% CI, 0.36-0.69; 

 mutations, rucaparib (n = 69) induced a median rPFS of 8.1 months vs 6.8 months for the control group (n = 34; HR, 0.97; 95% CI, 0.59-1.52; 

Among the intention-to-treat (ITT) population, inclusive of those with 

 mutations, those in the rucaparib arm (n = 270) experienced a median rPFS of 10.2 months, compared with 6.4 months for those in the control arm (n = 135; HR, 0.61; 95% CI, 0.47-0.80; 

“We believe that the positive results from TRITON3 further demonstrate the important role that [rucaparib] can play as a treatment option for men with metastatic CRPC associated with homologous recombination deficiency, and we look forward to submitting these data to the regulatory authorities in the US during [the first quarter of] 2023,” Patrick J. Mahaffy, president and chief executive officer of Clovis Oncology, stated in a press release.

“Not only does this provide a potential treatment option for eligible men with earlier stage disease, but it is the first and only PARP inhibitor that has demonstrated superior rPFS compared to chemotherapy, which is today the standard of care for these patients.”

In May 2020, the FDA granted rucaparib accelerated approval for the treatment of adult patients with 

 mutation (germline and/or somatic)—associated metastatic CRPC who have been treated with androgen receptor–directed therapy and a taxane-based chemotherapy, based on prior data from the phase 2 TRITON2 trial (NCT02952534).

The multicenter, open-label, randomized TRITON3 trial is a confirmation study for the current accelerated approval, and it will also serve as the basis for a supplemental new drug application for label expansion in the United States.

The trial enrolled patients who were at least 18 years old with histologically or cytologically confirmed, chemotherapy-naïve metastatic CRPC harboring a 

 mutation. Patients were also required to be surgically or medically castrated; be eligible for physician’s choice of comparator treatment with abiraterone acetate (Zytiga), enzalutamide (Xtandi), or docetaxel; and have disease progression following treatment with 1 next-generation androgen receptor–targeted therapy.

Key exclusion criteria included an active second malignancy except for non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer; prior treatment with a PARP inhibitor; prior chemotherapy for metastatic CRPC; or symptomatic and/or untreated central nervous system metastases.

Enrolled patients were randomly assigned to receive oral rucaparib daily or physician’s choice of treatment with abiraterone acetate, enzalutamide, or docetaxel.

Along with the primary end point of rPFS, secondary end points included overall survival (OS), objective response rate, duration of response, time to prostate-specific antigen (PSA) progression, PSA response, patient-reported outcomes, clinical benefit rate, and safety.

-mutation subgroup and ITT population favored rucaparib, though data were not yet mature. Mature OS data from the 

-mutation subgroup favored the control arm.

Regarding safety, findings from TRITON3 were consistent with rucaparib labeling. The most common treatment-emergent adverse effects (TEAEs) of grade 3 or higher for patients treated with rucaparib on the study included anemia/decreased hemoglobin (23.7%), neutropenia/decreased neutrophil count (7.4%), asthenia/fatigue (7.0%), thrombocytopenia/decreased platelet count (5.9%), and increased ALT/AST (5.2%).

TEAEs led to treatment discontinuation in 14.8% of patients who received rucaparib compared with 21.5% of patients in the control arm.

“Men with this type of metastatic prostate cancer want to get their genetically targeted therapy as early as possible, and this trial clearly shows the value of rucaparib as a treatment for these men,” Alan H. Bryce, MD, chair of the Division of Hematology and Medical Oncology at the Mayo Clinic and principal investigator of the TRITON3 trial, stated in a press release. “A key point is that rucaparib can replace chemotherapy in this setting. The current standard of care for these men is chemotherapy with docetaxel, and rucaparib is the only PARP inhibitor which has beaten a docetaxel-containing control arm in a clinical trial.”

TRITON3 phase 3 trial of Rubraca® (rucaparib) achieves primary endpoint in men with metastatic castration-resistant prostate cancer with BRCA Or ATM mutations. News release. Clovis Oncology. October 3, 2022. Accessed October 3, 2022. 

Rubraca® (rucaparib) approved in the U.S. as monotherapy treatment for patients with BRCA1/2-mutant, metastatic castration-resistant prostate cancer (MCRPC) who have been treated with androgen receptor-directed therapy and a taxane-cased chemotherapy. News release. Clovis Oncology. May 15, 2020. Accessed October 3, 2022. 

A study of rucaparib versus physician's choice of therapy in patients with metastatic castration-resistant prostate cancer and homologous recombination gene deficiency (TRITON3). ClinicalTrials.gov. Updated March 24, 2022. Accessed October 3, 2022. 

https://clinicaltrials.gov/ct2/show/NCT02975934

The median radiographic progression-free survival (rPFS) was 11.2 months among patients with castration-resistant prostate cancer who received rucaparib. In the control arm, median rPFS was 6.4 months.  

Rucaparib Boosts Radiographic Progression-Free Survival in Metastatic Castration-Resistant Prostate Cancer 

As the cancer treatment landscape continues to evolve, the role of front-line nurses in clinical trials remains essential, according to Anne Delengowski, RN, MSN, AOCN, CCCTM.

“I don’t know if nurses today can truly appreciate where we’ve come because they were never there, [but] I have had the honor and privilege of being there,” Delengowski, who has been an oncology nurse for 42 years, and is the director of Oncology Nursing Education at Thomas Jefferson University Hospital, said in an interview. “In the past, we had very few cancer drugs, we had minimal second-line therapies which are standard now, we didn’t have targeted therapy or immunotherapy, and we had poor symptom management.” 

Delengowski recently presented at the 2022 Oncology Nursing Society Bridge, highlighting notable improvements spanning the course of her career and the excitement that comes with being a part of a clinical trial from start to finish. In a post-presentation interview with 

®, Delengowski offered a personal perspective into how the field has changed during her career as a frontline nurse.

“When I first started as a cancer nurse, we didn’t have the antiemetics we have today, and it was awful. I did a study back then with a colleague from the school of nursing looking at anticipatory nausea and vomiting because the patients would come in vomiting prior to getting their drugs because they were anticipating it happening, [but] very rarely do you see that anymore. We [also] didn’t have growth factors; we didn’t have the colony stimulators to be able to prevent neutropenic fevers, so patients were hospitalized for most of the course of their disease. Today, all the stuff we talked about here came through clinical trials.”

She also highlighted how pain management strategies have significantly improved.

“I worked a lot in nightshift when I was in graduate school, and we didn’t have sustained release narcotics,” she said. “We used to have to wake people up in the middle of the night to give them pain medicine because if we didn’t their pain would be out of control in the morning. Once again, it was revolutionized that we have PCA [patient-controlled analgesia] pumps now, we have sustained release therapy. The nightmare of seeing patients in pain, you kind of weighed the fact if I didn’t wake them up, they’d be in a lot of pain in the morning and if I did wake them up, I interrupted their sleep, and it wasn’t good.”

Throughout her career, she shared that she has been inspired by the advances that clinical trials have brought about. She noted that patients are living longer, healthier lives, and that clinical trials are allowing providers to achieve “magical things.”

She noted, as an example, the breakthrough findings from Memorial Sloan Kettering Cancer Center where 100% of patients with rectal mismatch repair-deficient locally advanced rectal cancer achieved a complete response with dostarlimab-gxly (Jemperli).

Delengowski shared that, prior to working in clinical trials, she did not understand much about the process or have proper understanding or the extent of the behind-the-scenes work. For example, in her presentation, she explained how clinical trials must receive approval form a multidisciplinary disease group and a facilitation committee, along with a protocol review committee. In addition, there is a site initiation visit which provides the principal investigator and the team with training on all aspects of the trial, prior to its initiation.

Teamwork is also critical and research coordinators who understand the trial have been involved from the inception to guide nurses.

As part of her presentation, Delengowski outlined the different phases of clinical trials. Phase 1 trials are specifically designed to find a safe dose of a novel regimen for humans. This step determines how much a new treatment should be given (ie, oral or intravenous administration), and what the maximum-tolerated dose is.

Delengowski stressed, “A lot of times in phase 1 [trials] we don’t know what the symptoms or outcomes might be, so we need to be cognizant of the fact that anything that happens to that patient we need to document. We need to make sure we do it and we need to follow the protocol to dot the i, cross the t and do it all perfectly because if everyone chooses to do something different than it really doesn't make the trial valuable.”

“I remember giving my very first phase 1 [treatment] and I took a step back thinking ‘You want me to give this to a human being now? It’s the first time a human being has received this drug,’” she said. “I was humbled and wowed at the same time. It was wonderful for all involved, but a little frightening it was for us [as nurses] to administer.”

Phase 2 trials are larger and are designed to determine if the new treatment is effective against a certain cancer, as well as its safety profile. Phase 3 trials compare the new treatment (or new use of a treatment) against the current standard of care.

Across the trial continuum, supporting patients during the trial remains a significant part of the nurse’s role as patients can be overwhelmed throughout treatment. Delengowski highlighted that knowing where to get information for patients and helping to educate them is important for front-line nurses.

“It becomes very exciting when you know you’re part of [clinical trials],” she said. “Some frontline nurses may not exactly understand the value they bring, but [they’re] invaluable; We’re the frontline, we’re the last line, we’re the point where the person gets the medication or the therapy.”

However, phase 3 trials, which are usually randomized, can be difficult for nurses, because patients may not be happy to learn they were randomly assigned to receive the standard of care.

Delengowski explained “It's very hard when you talk up a study and the patient was randomized to standard of care. Often a frontline nurse will be confronted with [patients who say] ‘I signed on thinking I was going to get the new therapy and now I got standard of care drug.’ ”

“What I tell [patients] is in phase 3 studies we don’t know that standard care might be the best therapy. We don’t know and that’s what this is all about. I’ve been involved in phase 3 [trials], where the [experimental drug] was not better than standard of care; it was good, but not as good. It’s just part of the process and once you give that information to the patient, they feel a bit better about it.”

When looking back on all the various phases of clinical trials she has been a part of, Delengowski said it was an exciting feeling to think, “Wow, I was part of that, and we were there when it happened. Some of the trials didn’t come to fruition, but a lot of them did and when you look at that and know that you were part of it, it is so exciting…. As cancer nurses we see the patient go through from diagnosis to hopefully a long life, but in between there’s roadblocks. If they fail first-line therapy and other therapies and go onto a clinical trial, we walk that walk with them. I think that understanding that there is that next step [is important].”

Future steps in improving the clinical trial process include ensuring that inclusivity is a priority and that trials will be brought to the community. Historically, clinical trials have been performed in large academic centers which can be difficult to get to and exploring ways to bring them to patients and working with a community-based staff can be beneficial in making the clinical trials more comfortable for patients.

“[Clinical trials] give that glimmer of hope to someone that there may be other outcomes out there,” Delengowski said. “Even if it’s not something that’s going to be beneficial for that individual, which is not always the case, but it leads to phase 2 and phase 3 [trials] where there seemingly is some hope for a disease process that might not have had a whole lot of other options.”

Delengowski A. Clinical trials on the frontline: the changing landscape of clinical trials nursing. Presented at: ONS Bridge; September 13-15, 2022; virtual.

Cercek A, Lumish MA, Sinopoli JC, et al. Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer. 

. 2022;40(suppl 17):LBA5. doi:10.1200/JCO.2022.40.17_suppl.LBA5

Anne Delengowski, RN, MSN, AOCN, CCCTM, discusses the evolving role of the oncology nurse in clinical trial research.

Clinical Trials Continue to Propel Field of Oncology with Nurses on The Frontline

In September 2022, investigators published findings on an understudied stress associated with advanced cancer care—unmet death preferences. Many adolescent or young adult patients with cancer express that they would prefer to die at home; however, when combined with caregiver capabilities and necessary symptom management, most of these patients ultimately die in the hospital setting, underscoring an unmet need for this patient population.

Other topics in supportive care include a brief snapshot of cannabinoid products in the context of cancer-related pain management. During the 2022 ONS Bridge, Karen Hande, PhD(c), DNP, ANP-BC, CNE, FAANP, ANEF, offered an overview of what cannabinoid products are and what it means for patients to be taking consumed cannabidiol (CBD) vs marijuana, to improve cannabis-related dialogue between nurses and patients.

Moreover, September saw some key clinical updates in the gynecologic and genitourinary oncology spaces. Read below to see how immunotherapy is eliciting responses in urothelial carcinoma and how real-world patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer are achieving promising response with pembrolizumab (Keytruda) plus bevacizumab (avastin).

Better End-of-Life Options Are Needed for AYA Patients With Advanced Cancer

Innovative strategies are needed to ensure that adolescents and young adults with cancer who prefer to die at home can make that choice. Most adolescent or young adults (AYA) with advanced cancer prefer to die at home, according to results of a qualitative interview study published in 

Unfortunately, the desire of many of AYA patients is not realized with up to two-thirds of AYAs passing away in the hospital setting, underscoring an unmet need regarding death preferences in this population.

Oncology Nurses: What Cannabinoid Is Your Patient Taking?

In a presentation during the 2022 ONS Bridge, Karen Hande, PhD(c), DNP, ANP-BC, CNE, FAANP, ANEF, provided an overview of what some of the popular cannabinoid products are that patients with cancer may be taking.

Each month, we take a look back at the most popular Oncology Nursing News® stories. Here are the top 5 stories from September 2022.

Genitourinary Cancer