Continuing Education: August 2021

Release Date: August 22, 2021 Expiration Date: August 22, 2022 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/August2021

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

Colon: Real-World Analysis on Second-Line Cetuximab in mCRC Reveals Factors Linked With Longer Time on Treatment, OS

Liver: Regorafenib/Pembrolizumab Combination Yields Encouraging Results in Advanced HCC

Real-World Analysis on Second-Line Cetuximab in mCRC Reveals Factors Linked With Longer Time on Treatment, OS

By Courtney Marabella

In patients with metastatic colorectal cancer (mCRC) treated with cetuximab (Erbitux) as a second-line therapy after irinotecan or oxaliplatin-based regimens have failed, KRAS mutational status and geographical region were associated with time on treatment (TOT), while body mass index (BMI) and age were linked with overall survival (OS), according to data from a real-world retrospective analysis.

Results, which were presented during the virtual 2021 American Society of Clinical Oncology Annual Meeting, indicated that the median TOT in patients who received second-line cetuximab was 3.94 months (median interquartile range [mIQR], 3.51-4.40), while the median OS was 14.36 months (mIQR, 13.01-15.70).1

Moreover, receiving second-line treatment with cetuximab plus FOLFIRI (Leucovorin, fluorouracil, irinotecan) (median TOT = 4.43 months; mIQR, 3.71-5.36), having KRAS wild-type status, and receiving second-line cetuximab following frontline capecitabine plus oxaliplatin (CapeOX), were all associated with a longer median TOT. Furthermore, residing in the South region vs the Midwest of the United States was linked with a shorter median TOT.

Having a higher BMI was associated with a longer median OS (obese vs underweight HR, 0.46; 95% CI, 0.32-0.66), while receiving treatment with second-line FOLFOX (cetuximab plus 5-fluorouracil, leucovorin, and oxaliplatin) was linked with a shorter median OS (10.97 months; mIQR, 5.55-14.06). Additionally, age greater than 65 years was also linked with a shorter median OS (≥ 65 years vs < 65 years; HR, 1.24; 95% CI 1.05-1.46).

Anti-epidermal growth factor receptor drugs are being increasingly utilized in later lines of therapy in patients with mCRC, but the real-world TOT and OS of patients who receive cetuximab in the second-line setting has not been examined. As such, investigators set out to examine characteristics linked with TOT and OS using retrospective, observational data.

Between January 2013 and August 2020, 1011 patients were selected from the nationwide Flatiron electronic health record database. Patients were included in the analysis if they had a mCRC diagnosis, received second-line treatment with a cetuximab-based regimen, and had progressed on oxaliplatin/irinotecan-based regimens in the front line.

Investigators defined TOT as the time from start of cetuximab in the second line to the last date of evidence of administration. End of treatment was defined if patients progressed to a third line of therapy or if they had a death record. Additionally, OS was calculated from index date to the date of death or censored to the last visit date available.

Among the 1011 patients included in the analysis, more than half were younger than 65 years (58%) and male (60%). Additionally, patients had a median BMI of 26.6 kg/m², had previously received FOLFOX regimens in the first-line setting (61%), and received treatment in the community setting (96%). The most frequently used second-line treatment regimens were cetuximab plus FOLFIRI (46%) and cetuximab plus irinotecan (29%).

Reference

1. Gathirua-Mwangi W, Yang T, Khan T, et al. Real-world time on treatment and overall survival in patients with metastatic colorectal cancer receiving cetuximab in second line after failing irinotecan or oxaliplatin-based regimens. J Clin Oncol. 2021;39(suppl 15):e15568. doi:10.1200/JCO.2021.39.15_suppl.e15568

Regorafenib/Pembrolizumab Combination Yields Encouraging Results in Advanced HCC

By Conor Killmurray

The combination of regorafenib plus pembrolizumab in the first-line setting for patients with advanced hepatocellular carcinoma showed encouraging antitumor activity with a disease control rate of 88-91%, and did not display any new safety signals.

The combination of regorafenib (Stivarga) plus pembrolizumab (Keytruda) in the first-line setting for patients with advanced hepatocellular carcinoma (HCC) showed encouraging antitumor activity with a disease control rate (DCR) of 88-91%, and did not display any new safety signals, according to updated data presented during the virtual 2021 American Society of Clinical Oncology Annual Meeting.1

Researchers looked at combining the 2 individual therapies, previously approved as monotherapies for patients with advanced HCC who progressed on sorafenib (Nexavar), in a phase 1b study (NCT03347292) that evaluated 57 patients with advanced HCC who had no prior systemic therapy. Treatment in the first cohort (n = 35) consisted of 120 mg of regorafenib daily on a 3 week on, and 1 week off schedule, and 200 mg of pembrolizumab given intravenously every 3 weeks. Treatment was planned to either escalate to 160 mg or lower to 80 mg of regorafenib, but only an exploratory cohort (n = 22) received 80 mg due to a high volume of dose modification in the 120 mg cohort. At the data cut off, 50% of the patients in the 80-mg cohort remained on treatment.

Response rates among both cohorts were similar; 31% of patients had an objective response rate (ORR) in the 120 mg cohort and patients in the 80 mg cohort had an ORR of 32%. Moreover, the 80 mg cohort had a median follow up of 10 months and displayed a median progression-free survival (PFS) of 6.9 months (95% CI, 3.8, not estimated [NE]) and a median time-to-progression (TTP) of 6.9 months (95% CI 2.9, NE), with insufficient follow up for overall survival (OS) data. In the 120 mg cohort, after a median follow up of 13.9 months, median OS, PFS, and TTP, was 26.5 months (95% CI 11.4, NE), 7.5 months (95% CI 4.1, 11.7), and 8.1 months (95% CI 4.1, 23.9), respectively.

Out of 32 evaluable patients in the 120-mg cohort 31% of patients had a partial response and 56% had stable disease with a DCR of 88%. Twenty-two patients in the 80-mg cohort had a higher DCR at 91% with 32% showing partial responses and 59% had stable disease.

“Overall, 57 patients were treated,” said Anthony B. El-Khoueiry, MD, from the Keck School of Medicine, University of Southern California, and lead investigator of the study, at a virtual presentation of the data at the 2021 American Society of Clinical Oncology meeting.2 “At baseline, most patients had an ECOG Performance Status of 0. All patients had Child-Pugh A and approximately 80% were BCLC [Barcelona Clinic Liver Cancer] stage C. And two-thirds had extrahepatic disease and/or microvascular invasion.”

In comparing the 2 cohorts, the 80-mg cohort had a more favorable safety profile and lower rates of dose reductions and treatment interruptions, according to El-Khoueiry. In the 120-mg cohort, two-thirds of patients had a treatment-emergent adverse event (TEAE) that led to interruption of treatment or dose reduction. Grade 3 or 4 TEAE occurred in 86% of patients in the 120-mg cohort compared with 55% in the 80-mg cohort. The most common grade 1-2 TEAEs in both cohorts included fatigue, diarrhea, increased bilirubin, and increased lipase. The majority of grade 3 to 5 TEAE were linked with regorafenib in the 120-mg cohort at 74% of TEAEs compared with 51% in pembrolizumab, however, in the 80-mg cohort 41% of grade 3 to 5 TEAEs were related to regorafenib compared with 23% in pembrolizumab.

“There was no apparent association between regorafenib exposure and objective tumor response, and there was substantial overlap in individual exposures,” explained El-Khoueiry when talking about an additional biomarker analyses researchers completed. “The biomarker analyses were limited by small sample size and lack of power to compare the 2 dose levels. Nonetheless, we did see a decrease in the ratio of CD4-positive to CD8-positive T cells from baseline, which was more apparent in the 120-mg cohort.”

References

1. El-Khoueiry A, Kim R, H W, et al. Updated results of a phase 1b study of regorafenib (REG) 80 mg/day or 120 mg/day plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC). J Clin Oncol. 2021;39(suppl 15; abstr 4078). doi: 10.1200/JCO.2021.39.15_suppl.4078
2. El-Khoueiry A, Kim R, H W, et al. Updated results of a phase 1b study of regorafenib (REG) 80 mg/day or 120 mg/day plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC). Presented at: 2021 American Society of Clinical Oncology Annual Meeting; June 4-8, 2021; Virtual. Abstract 4078.