Continuing Education: October 2021

Release Date: October 22, 2021½ Expiration Date: October 22, 2022½ This activity is provided free of charge.

STATEMENT OF NEED

This CE article is designed to serve as an update on cancer detection and prevention and to facilitate clinical awareness of current and new research regarding state-of-the-art care for those with or at risk for cancer.

TARGET AUDIENCE

Advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients may participate in this CE activity.

EDUCATIONAL OBJECTIVES

Upon completion, participants should be able to:

1. Describe new preventive options and treatments for patients with cancer
2. Identify options for individualizing the treatment for patients with cancer
3. Assess new evidence to facilitate survivorship and supportive care for patients with cancer

ACCREDITATION/CREDIT DESIGNATION STATEMENT

Physicians' Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669 for 0.5 Contact Hour.

DISCLOSURES/RESOLUTION OF COI

It is the policy of Physicians' Education Resource®, LLC (PER®) to ensure the fair balance, independence, objectivity, and scientific objectivity in all of our CE activities. Everyone who is in a position to control the content of an educational activity is required to disclose all relevant financial relationships with any commercial interest as part of the activity planning process. PER® has implemented mechanisms to identify and resolve all conflicts of interest prior to release of this activity.

The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial interests pertaining to this activity.

METHOD OF PARTICIPATION

1. Read the articles in this section in their entirety.

2. Go to www.gotoper.com/go/October2021

3. Complete and submit the CE posttest and activity evaluation.

4. Download/Print your CE Certificate

OFF-LABEL DISCLOSURE/DISCLAIMER

This CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CE activity is for continuing medical nursing purposes only and is not meant to substitute for the independent medical judgment of a nurse or other health care provider relative to diagnostic, treatment, or management options for a specific patient's medical condition.

The opinions expressed in the content are solely those of the individual authors and do not reflect those of PER®

Table of Contents

Breast: Personalized Screenings Are Needed to Address Racial Disparities in Breast Cancer Outcomes

Liver: Checkpoint Inhibitor/TKI Combos in the Frontline Setting Improve Outcomes in Renal Cell Carcinoma

Personalized Screenings Are Needed to Address Racial Disparities in Breast Cancer Outcomes

“We want to make sure we can provide the right treatment for the right patient at the right time,” said Olufunmilayo I. Olopade, MD, FACP.

By Jason Harris

“Smarter screening” strategies may play a crucial role in helping Latina and Black women survive breast cancer at the same rates as their White counterparts, according to a presenter at the 5th Annual School of NursingOncology™ virtual conference, held August 6 to 7, 2021.¹

During her keynote speech, Olufunmilayo I. Olopade, MD, FACP, American Cancer Society clinical research professor and director of the University of Chicago’s Center for Clinical Cancer Genetics and Global Health, in Illinois, stressed the need to better understand how breast cancer affects Latina and Black women to improve their survival outcomes following treatment.

“We want to make sure we can provide the right treatment for the right patient at the right time,” explained Olopade.She told the attendees that screening has been an effective tool for reducing breast cancer deaths. However, her research shows that although Black women in and around the Chicago area undergo screening at rates higher than the national average, they still have poorer survival outcomes than White women—even though the 2 groups achieve pathologic complete responses at similar rates.

Over time, Olopade said, results of genomic assays have revealed that that breast cancer is not merely a single disease. Furthermore, she has concluded that screening for early detection of breast cancer should no longer be age based.

“‘Everyone starts screening at 40,’ [but] there are some women who would have had breast cancer that would have the potential to kill them before they ever get that first mammogram. That’s why we’re going away from talking about age-based screening to begin to say, ‘Let us personalize screening. Let us all figure out what exactly we are at risk for. Are we at risk for a ‘cheetah’ type of cancer? Or are we at risk for a ‘snail’ type of cancer that grows very slowly?’”

Olopade has studied patterns of inherited breast cancer in women in Nigeria, Cameroon, Uganda, and Brazil, as well as among Black women in the United States. Those data, along with findings from the 12 US population-based studies in the CARRIERS consortium, which included 32,247 women with breast cancer and 32,544 controls, show that BRCA1, BRCA2, and PALB2 are the most important genes for assessing breast cancer riskin Black and Latina women.²

“We cannot use a one-size-fits-all [approach] and then say, ‘Oh, but you know, BRCA1 and BRCA2 are not important.’ They are important. It all depends on your population,” she said. Determining a patient’s individual risk is challenging, in part because Black women tend to be underrepresented in clinical trials in the United States and abroad, but genomic testing for precision risk assessment will help transform cancer care, Olopade said.

This is where investigators can improve outcomes, she continued. Physicians can calculate a polygenic risk score (PRS) for an individual based on the presence or absence of risk variants in multiple cancer predisposition genes identified in large genome-wide association studies. Each risk variant has limited predictive power by itself, but the combined effect of the large number of variants in a PRS allows population risk stratification, or the assignment of patients to different categories of breast cancer risk. PRSs can provide better insight than traditional risk models, especially in these populations. Olopade described a new breast cancer risk model that was developed specifically for Black and Brown women; the strength of its predictive power is relative to the proportion of African ancestry in a patient’s DNA.

We’re talking about deescalating—not just using more and more treatment. [Similarly,] we have to deescalate in what we’re doing for early detection. We have to use innovations.”

References

1. Olopade OI. Retooling precision oncology for true equity of cancer care. Presented at: 5th Annual School of Nursing Oncology; August 6-7, 2021; Virtual.
2. Hu C, Hart SN, Gnanaolivu R, et al. A population-based study of genes previously implicated in breast cancer. N Engl J Med. 2021;384(5):440-451. doi:10.1056/NEJMoa2005936

Checkpoint Inhibitor/TKI Combos in the Frontline Setting Improve Outcomes in Renal Cell Carcinoma

Recently approved combination therapies have contributed to significantly improved
survival rates in renal cell carcinoma.

By Gina Mauro

The evolution of checkpoint blockade and VEGF TKIs, as well as the regulatory approval of combination therapies involving these inhibitors, has led to a significant improvement in outcomes for patients with renal cell carcinoma (RCC).¹

“[We see that] there is a definitive role in having dual therapy,” said Laura S. Wood, MSN, RN, OCN, Renal Cancer Research Coordinator at Cleveland Clinic Taussig Cancer Center, in Ohio, during a presentation at the 5th Annual School of NursingOncologyTM conference, held August 6 to 7, 2021. “We’re seeing a number of new combinations with PD-1/PD-L1 inhibitors plus 1 of our TKIs, so the story continues as far as the evolution of our therapies. And this is what will account for improvements in response rate, progression-free survival, and overall survival.”

The shifted balance of treatment toward anticancer immunity with combination strategies involving PD-1/PD-L1, often paired with VEGF inhibitors, has been demonstrated by the results of several pivotal clinical trials that have led to improved outcomes in RCC: CheckMate 214 (NCT02231749), KEYNOTE-426 (NCT02853331), CheckMate 9ER (NCT03141177), and CLEAR (NCT02811861).

Pivotal Phase 3 Trials in RCC

CheckMate 214

The phase 3 CheckMate 214 trial was the basis for the April 2018 FDA approval of nivolumab/ipilimumab as first-line treatment for patients with intermediate- and poor-risk RCC.²

In the trial, patients with advanced clear cell RCC were randomized to receive 3 mg/kg nivolumab plus 1 mg/kg ipilimumab or sunitinib monotherapy as first-line treatment. At a median follow-up of 55 months, the combination led to a 31% reduction in risk of death compared with sunitinib (Sutent) in the intent-to-treat population.³ Specifically, median overall survival (OS) was not reached with nivolumab/ipilimumab and was 38.4 months with sunitinib (HR, 0.69; 95% CI, 0.59-0.81).

The median progression-free survival (PFS), however, was 12.2 months and 12.3 months, respectively (HR, 0.89; 95% CI, 0.76-1.05). The overall response rates (ORRs) were 39% and 32% (P = .0134), and the complete response (CR) rates were 11% vs 3%, respectively.

In patients with intermediate- and poor-risk disease, OS was also superior in the nivolumab/ipilimumab group (48.1 months) compared with sunitinib (26.6 months; HR, 0.65; 95% CI, 0.54-0.78).

KEYNOTE-426

Pembrolizumab and axitinib combination therapy was tested up front in the phase 3, open-label KEYNOTE-426 trial, in which treatment-naïve patients with advanced clear cell RCC were randomized to receive the PD-1/VEGF TKI combination or sunitinib.

Extended follow-up (median 30.6 months) results showed that median OS was not reached with pembrolizumab/axitinib compared with 35.7 months with sunitinib (HR, 0.68; 95% CI, 0.55-0.85; P = .0003).⁴ Additionally, the median PFS was 15.4 months and 11.1 months, respectively (HR, 0.71; 95% CI, 0.60-0.84; P < .0001). The combination elicited a 60% ORR, whereas sunitinib’s ORR was 40% (P < .0001), and the CR rates were 9% and 3%, respectively.

Based on earlier data from KEYNOTE-426, the FDA approved pembrolizumab and axitinib in the up-front setting for patients with RCC in April 2019.⁵

CheckMate 9ER

In the international phase 3 CheckMate 9ER trial, investigators evaluated nivolumab plus cabozantinib compared with sunitinib in the frontline setting for patients with advanced clear cell RCC.

At a median follow-up of 23.5 months, median OS with the combination was not reached vs 29.5 months with sunitinib (HR, 0.66; 95% CI, 0.50-0.87; P = .0034), and the median PFS was doubled at 17.0 months vs 8.3 months with sunitinib (HR, 0.52; 95% CI, 0.43-0.64; P <.0001).⁶ The ORRs were 55% and 27% with nivolumab/cabozantinib and sunitinib and the CR rates were 9% vs 4%, respectively.

The FDA approved nivolumab plus cabozantinib in this setting in January 2021 based on earlier phase 3 CheckMate 9ER data.⁷ Nivolumab is administered via a 30-minute intravenous infusion at a recommended dose of either 240 mg every 2 weeks or 480 mg every 4 weeks. Combined with oral cabozantinib at 40 mg once daily without food, the regimen is taken until either progressive disease or intolerable toxicity.

CLEAR

The phase 3 CLEAR trial compared lenvatinib (Lenvima) plus pembrolizumab vs sunitinib for the frontline treatment of RCC. Efficacy data were recently presented at the 2021 ASCO Genitourinary Cancers Symposium.^8,9

At a median follow-up of 27 months, pembrolizumab/lenvatinib had a 34% reduction in risk of death compared with sunitinib; median OS was not reached in either arm (HR, 0.66; 95% CI, 0.49-0.88; P = .005). The median PFS was 23.9 months and 9.2 months, respectively (HR, 0.39; 95% CI, 0.32-0.49; P < .0001); the ORRs were 71% vs 36% (OR, 4.35, 95% CI, 3.16-5.97; P < .0001), and the CR rates were 16% vs 4%, respectively. In addition, investigators tested the efficacy and safety of lenvatinib plus everolimus (Afinitor) vs sunitinib in this setting in a separate cohort. The data showed statistically significant improvements in PFS and ORR, but not in OS (HR, 1.15; 95% CI, 0.88-1.50; P = .2975).

Based on the CLEAR findings, the FDA approved lenvatinib plus pembrolizumab as frontline treatment for patients with advanced RCC.

“What’s important to note is that even though [this combination] has 1 of the shorter overall durations of evaluation [to date], [it has a] 71% overall response rate and 16% complete response rate in just 27 months of follow-up for patients on active treatment,” Wood explained. “We’re continuing to see improvements in combinations and improvements in outcomes for these regimens.”

References

1. Wood LS. Renal cell carcinoma and supportive care in GU cancers. Presented at: 5th Annual School of Nursing Oncology; August 6-7, 2021; Virtual.
2. FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma. News release. FDA. April 16, 2018. Accessed March 29, 2021. https://bit.ly/2QEirhF
3. Albiges L, Tannir NM, Burotto M, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open. 2020;5(6):e001079. doi:10.1136/esmoopen-2020-001079
4. Powles T, Plimack ER, Soulières D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 2020;21(12):1563-1573. doi:10.1016/S1470-2045(20)30436-8
5. FDA approves Bavencio (avelumab) plus Inlyta (axitinib) combination for patients with advanced renal cell carcinoma. News release. Pfizer Oncology. May 14, 2019. Accessed August 9, 2021. https://on.pfizer.com/2HtdCzF
6. Motzer RJ, Choueiri TK, Powles T, et al. Nivolumab + cabozantinib (NIVO+CABO) versus sunitinib (SUN) for advanced renal cell carcinoma (aRCC): outcomes by sarcomatoid histology and updated trial results with extended follow-up of CheckMate 9ER. J Clin Oncol. 2021;39(suppl 6):308. doi:10.1200/JCO.2021.39.6_suppl.308

Exelixis Announces U.S. FDA Approval of CABOMETYX® (cabozantinib) in Combination with OPDIVO® (nivolumab) as a First-Line Treatment for Patients with Advanced Renal Cell Carcinoma. Published online January 22, 2021. Accessed January 22, 2021. https://bwnews.pr/3c2w2bf.

1. Motzer RJ, Porta C, Eto M, et al. Phase 3 trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) or everolimus (EVE) versus sunitinib (SUN) monotherapy as a first-line treatment for patients (pts) with advanced renal cell carcinoma (RCC) (CLEAR study). J Clin Oncol. 2021;39(suppl_6):269. doi:10.1200/JCO.2021.39.6_suppl.269
2. Motzer R, Alekseev B, Rha SY, et al; CLEAR Trial Investigators. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716
3. FDA approves KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) combination for first-line treatment of adult patients with advanced renal cell carcinoma (RCC). News release. Merck. August 11, 2021. Accessed August 11, 2021. https://bwnews.pr/3fXk8Rj