A post-hoc analysis of the phase 3 REFLECT trial (NCT01781266) indicated that patients with unresectable hepatocellular carcinoma (uHCC) with Child-Pugh class B (CP-B) liver function fared similarly to their Child-Pugh class A (CP-A) counterparts who received lenvatinib (Lenvima). The tumor size reduction was similar between the 2 groups, according to an analysis presentated at the 2021 European Society for Medical Oncology World Congress on Gastrointestinal Cancer.

“The results of this post hoc analysis suggest that patients with uHCC whose liver function deteriorates to CP-B after initiation of therapy may continue to receive lenvatinib,” the researchers wrote.

Results from the randomized, multicenter phase 3 REFLECT study– which led to the FDA’s approval of the agent for the first-line treatment of patients with uHCC – showed a benefit from lenvatinib, compared with sorafenib (Nexavar), irrespective of baseline liver function, including albumin-bilirubin (ALBI) grade 1 or 2 and CP score of 5 or 6.

However, of note, the trial enrolled patients with CP-A liver function per the study inclusion criteria, but not CP-B specifically.

“In the absence of any initial enrollment of patients with CP-B liver function, we conducted a post hoc exploratory analysis of key efficacy and safety outcomes in patients from REFLECT whose liver function had deteriorated to CP-B versus those whose liver function remained CP-A within 8 weeks post-randomization.”

The post hoc analysis assessed overall response rate (ORR), and landmark analyses that began after week 8, including progression-free (PFS) and overall survival (OS), both in patients whose liver function had deteriorated to CP-B and in patients whose liver function remained CP-A within 8 weeks post-randomization. In addition, safety was evaluated from baseline and adjusted by treatment duration.

Among patients treated with lenvatinib in the CP-B (n = 60) and CP-A (n = 413) subgroups, the median percent changes in tumor size from baseline to week 8 were –16.2% (range, –100 to 25) and –15.9% (range, –100 to 187), respectively, compared with 1.7% (range, –36 to 64) and 0% (range, –100 to 106) in patients treated with sorafenib in the CP-B (n = 47) and CP-A (n = 427) subgroups.

In the lenvatinib group, the CP-B and CP-A subgroups demonstrated ORRs of 28.3% (95% CI, 16.9-39.7) and 42.9% (95% CI, 38.1-47.6), respectively. In particular, for the CP-B subgroup of the lenvatinib arm, there were 0 complete responses (CRs), 17 (28.3%) partial responses (PRs), 17 (28.3%) patients with stable disease (SD), 12 (20.0%) with progressive disease (PD), and 14 (23.3%) were not evaluable (NE), compared with 10 (2.4%) CRs, 167 (40.4%) PRs, 142 (34.4%) with SD, 67 (16.2%) with SD, and 27 (6.5%) NE for the CP-A subgroup.

In the sorafenib group, the CP-B and CP-A subgroups demonstrated ORRs of 8.5% (95% CI, 0.5-16.5) and 12.9% (95% CI, 9.7-16.1), respectively. In particular, for the CP-B subgroup of the sorafenib arm, there were 0 CRs, 4 (8.5%) PRs, 12 (25.5%) with SD, 23 (48.9%) with PD, and 8 (17.0%) NE, compared with 4 (0.9%) CRs, 51 (11.9%) PRs, 207 (48.5%) with SD, 129 (30.2%) with PD, and 36 (8.4%) NE.

After week 8, median OS was 6.8 months (95% CI, 2.6-10.3) and median PFS was 3.7 months (95% CI, 1.8-7.4) in lenvatinib-treated patients within the CP-B subgroup, compared with 13.3 months (95% CI, 11.6–16.1) and 6.5 months (95% CI, 5.6–7.4), respectively, in the CP-A subgroup. In the sorafenib-treated CP-B subgroup, median OS and PFS were 4.5 months (95% CI, 2.9–6.1) and 0.5 months (95% CI, 0.1–3.6), respectively, compared with 12.0 months (95% CI, 10.2–14.0) and 3.6 months (95% CI, 0.1–3.6) in the CP-A subgroup.

In the CP-B and CP-A subgroups treated with lenvatinib, the median duration of treatment was 3.2 months (range, 0.3-31.5) and 6.9 months (range, 0.0-35.0), respectively, compared with 1.9 months (range, 1.9 months (range, 0.2-22.4) and 3.7 months (range, 0.1—38.7) in the sorafenib-treated CP-B and CP-A subgroups.

The mean dose intensity of lenvatinib was 8.4 mg/day/patient (standard deviation [SD], 3.07) and 9.5 mg/day/patient (SD, 6.01) in the CP-B and CP-A subgroups, respectively, whereas the mean dose intensity of sorafenib was 653.2 mg/day/patient (SD, 165.75) and 664.8 mg/day/patient (SD, 174.23) in the CP-B and CP-A subgroups, respectively.

Among the CP-B and CP-A patients, rates for grade 3 or higher treatment-related adverse events (TRAEs) in the lenvatinib arm were 3.65% (n = 95) and 1.41% (n = 419), respectively, and 3.38% (n = 42) and 1.71% (n = 388), respectively, in the sorafenib arm.

In their conclusion, the researchers noted, “As this post hoc analysis is limited by its descriptive nature, the efficacy results cannot be compared between CP–B and CP–A subgroups,” adding that further investigation is warranted.

“Although the treatment landscape for patients with unresectable hepatocellular carcinoma (uHCC) has recently expanded, there remains an unmet need for effective treatment options in patients with Child–Pugh class B (CP-B) liver function. Such patients are rarely included in clinical trials,” the researchers wrote in their poster.

In the trial, patients with uHCC were randomly assigned 1:1 to receive lenvatinib – for which dosage was based bodyweight: 12 mg/day for those weighing ≥ 60 kg; 8 mg/day for those weighing < 60 kg) – or sorafenib 400 mg twice daily in 28-day cycles.

At baseline, patients whose liver function deteriorated to CP-B within 8 weeks in the lenvatinib and sorafenib arms, 73.3% and 61.7%, respectively, had an ALBI score of 2, and 60.0% and 44.7% had a CP score of 6. Similarly, among those whose liver function remained CP-A within 8 weeks in both arms, 73.1% and 75.4%, respectively, had an ALBI score of 1, and 83.5% and 78.5% had a CP score of 5.

In the prior analysis, treatment with lenvatinib demonstrated higher ORR, compared with sorafenib, in patients with a CP score of 5 (OR, 4.88; 95% CI, 3.37-7.08) and in those with a CP score of 6 (OR, 5.25; 95% CI, 2.32-11.85), as well as in patients classified as either ALBI grade 1 (OR, 5.48; 95% CI, 3.70-8.10) or ALBI grade 2 (OR, 5.37; 95% CI, 2.61-11.06).

Huynh J, Thet Cho M, Jae-Hoon Kim E, Ren M, Amaya-Chanaga C, Vogel A. Post hoc analysis in patients with unresectable hepatocellular carcinoma who progressed to Child–Pugh B liver function in the phase 3 REFLECT study of lenvatinib vs sorafenib. 

. 2021;32(suppl 3) doi:10.1016/j.annonc.2021.05.133

This article was originally published on OncLive as 

“Lenvatinib Treatment Can Continue in Unresectable HCC With Child–Pugh Class-B Liver Function”

Articles

Researchers observed a similar tumor size reduction between 2 arms of patients with hepatocellular carcinoma who were stratified by their liver function class and treated with lenvatinib.  

Patients with Unresectable Hepatocellular Carcinoma with Moderately Impaired Liver Function May Continue Lenvatinib Therapy  

Adjuvant carboplatin and paclitaxel after standard cisplatin-based chemoradiation did not demonstrate improved overall survival or progression-free survival in patients with locally advanced cervical cancer, according to findings from the phase 3 OUTBACK trial that were presented at the 2021 ASCO Annual Meeting.

“Adjuvant chemotherapy given after standard platinum-based chemoradiation for women with locally advanced cervical cancer did not improve OS or PFS. So, the standard treatment should continue to be pelvic chemoradiation with concurrent weekly cisplatin,” lead study author Linda R. Mileshkin, MD, medical oncologist, Peter McCallum Cancer Centre, Melbourne, Australia, said during a presscast ahead of the meeting.

“Our findings don't support giving adjuvant chemotherapy with carboplatin and paclitaxel after chemoradiation with weekly cisplatin. Further research should focus on adjuvant therapies that might be more tolerable and effective when given after standard therapy,” she added.

In the international, randomized phase 3 OUTBACK trial (NCT01414608), the investigators aimed to determine the survival effects from administering adjuvant chemotherapy after standard chemoradiation, compared with standard chemoradiation alone, in 919 patients with locally advanced cervical cancer recruited from April 2011 to June 2017

In total, investigators randomized patients 1:1 to receive either standard cisplatin-based chemo-radiation followed by adjuvant chemotherapy (n = 463) with 4 cycles of carboplatin and paclitaxel or standard cisplatin-based chemo-radiation (n = 456). Adjuvant chemotherapy was administered in 361 women (78%).

Trial eligibility consisted of locally advanced cervical cancer (FIGO 2008 stage IB1 & node positive, IB2, II, IIIB, or IVA); an ECOG score of 0 to 2; squamous cell, adenocarcinoma, or adenosquamous cancer; no nodal disease above L3/4; and disease that was suitable for primary treatment with chemo-radiation with curative intent. Women were stratified by nodal status, participating site, FIGO stage, age, and planned extended-field radiotherapy.

OS at 5 years served as the primary end point. Secondary endpoints included PFS, adverse events (AEs), and patterns of disease recurrence.

Median follow-up was 60 months (IQR, 45-65).

The adjuvant chemotherapy arm demonstrated similar OS at 5 years, compared with the control arm (72% vs 71%, respectively; P = .8), for an HR of 0.90, (95% CI, 0.70-1.17), as well as similar PFS at 5 years (63% vs 61%; P = .61), for an HR of 0.87 (95% CI, 0.70-1.08).

In addition, patterns of disease recurrence were similar in the two treatment groups.

“Even when we looked at subsets of women with high-risk disease, such as those with node positive involvement, there was no benefit from the intervention,” Mileshkin added.

Within a year of randomization, grade 3 to 5 AEs typically seen with chemotherapy occurred in significantly more patients in the adjuvant chemotherapy arm, compared with the control arm (81% vs 62%, respectively). Lastly, Mileshkin noted that quality of life was worse during adjuvant chemotherapy and for the following 3 to 6 months, but returned to being similar between the groups from 12 months onwards.

Cervical cancer is a major global health problem, according to Mileshkin, with more than half a million women diagnosed with the disease each year, “and more than 3000 women will die of this cancer each year, making it the fourth leading cause of cancer-related death in women. … But most women die from cervical cancer…because of the development of distant metastatic disease.”

Although prior, smaller studies suggested that giving more chemotherapy after chemoradiation could improve survival. “And these findings changed practice in some centers,” Mileshkin explained. “However, the international community felt that there were some flaws in these trials and that it was important to perform a confirmatory trial.”

ASCO president Lori J. Pierce, MD, FASTRO, FASCO, added to the OUTBACK trial’s significance. “As we heard, physicians are currently using adjuvant chemotherapy based upon preliminary data and promise it could work. We clearly see it does not work and need to discontinue that practice,” she said. “This tells us that, as clinical researchers, we need more trials for patients with locally advanced cervical cancer using a different therapeutic approach. And I think it also clearly shows the importance of the outcomes of clinical trials, even if the results are negative. Both positive trials and negative trials clearly inform practice.”


Mileshkin LR, MooreKN, Barnes E, et al. Adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: The randomized phase 3 OUTBACK Trial (ANZGOG 0902, RTOG 1174, NRG 0274). Presented at: American Society of Clinical Oncology Annual Meeting; June 4-8, 2021; Virtual. Abstract LBA3.

This article was originally published on OncLive as, "

Adjuvant Chemotherapy Fails to Improve PFS and OS in Locally Advanced Cervical Cancer.

Adjuvant carboplatin and paclitaxel after standard cisplatin-based chemoradiation did not demonstrate improved overall survival or progression-free survival in patients with locally advanced cervical cancer.

Adjuvant Chemo Does Not Improve Survival in Locally Advanced Cervical Cancer

Implementation of an onboarding reference guide served as a useful resource for advanced practice providers (APPs) in treating patients who are undergoing bone marrow transplantation (BMT), according to a poster presentation at the 46th Annual ONS Congress.

“It is known that bone marrow transplant patients are quite complex and require careful management by their providers. As cancer services continue to expand across organizations, advanced practice providers, or APPs, are playing a central role in patient care,” Tanya Lalani, DNP, NP, AOCNP®, a nurse practitioner at Ochsner Health said during a recording at the meeting. “Organizations are growing rapidly and more and more APPs are being hired.”

With this expansion, for example at Ochsner Health, it has become apparent that a structured orientation is necessary to allow for appropriate training for APPs, Lalani added. As a result, she created an onboarding reference guide, also known as the cheat sheet for new BMT APP hires, for reference during and after their orientation period.

In particular, the guide includes step-by-step information on how to perform daily tasks like admissions, discharges, and graft versus host disease documentation. In addition, it includes important phone numbers, frequently used order codes, and the process for performing and documenting procedures, as well as common labs and advanced testing guidelines for BMT patients categorized by hematologic malignancy.

In particular, Lalani added that the guide includes a checklist and a shadowing schedule, which allows an APP to know exactly where they need to be at any given.

Lastly, the guide also includes a quiz to help with discussion points during the orientation period.

Since its implementation, the guide is updated frequently to allow for the most up-to-date information, Lalani said.

“This onboarding guide has been very well received by new hires as well as management,” she concluded. “It has been used by leadership when asking the system for new hires. It has inspired other departments within the organization to create a more structured orientation guide as well. It has also been shared with hematology oncology fellows, and there are future plans to share it with internal medicine residents who rotate through the bone marrow transplant service.”

Lalani T, et al. An Onboarding Reference Guide for New Bone Marrow Transplant Advanced Practice Providers. Presented at: 46th Annual ONS Congress; April 20, 2021; virtual.

The “cheat sheet” assisted advanced practice providers using a step-by-step guide that is updated frequently to allow for the most up-to-date information.

Onboarding Reference Guide Aids APPs Treating Patients Receiving Bone Marrow Transplant

Nurses showed a willingness to learn about patients who identify as lesbian, gay, bisexual, and transgender (LGBT); however, they also reported there is a need for such training, according to survey results presented at the Oncology Nursing Society 43rd Annual Congress.

In scientific and health literature, sexual minorities include individuals who identify as lesbian, gay, bisexual, pansexual, asexual, or queer; gender minorities include those who identify as transgender, transman, transwoman, nonbinary, genderfluid, or queer.

“These terms allow us to encompass sexual orientations (in research) without limiting it at any point,” explained Chasity Burrows Walters PhD, RN, director, patient and caregiver engagement at Memorial Sloan Kettering (MSK) Cancer Center in New York, New York. “Sex is not gender. They are very different. This matters a lot to us in health care because when we think about biology we need to think about anatomy, and in oncology care, this matters for screening purposes.”

Population surveys have suggested between 5.2 and 9.5 million US adults identify as LGBT, but barriers to equitable health care are multifactorial, including negative experiences.

While research demonstrates there have been increasing efforts to educate nursing students in this area, other studies have shown that barriers still persist. For example, sexual and gender minorities have barriers to healthcare like discrimination, insurance, and provider/healthcare system insensitivity. Gender minorities also experience distress from discordance between gender and genitalia, lack of evidence for clinical decision making, and limited exposure, Walters said.

In addition, the LGBT population lacks data in the cancer space, despite the fact that there are overlapping risk factors that can lead to anal, breast, cervical, colorectal, endometrial, lung, and prostate cancers in this group. “We don’t have anything to [reference] to learn about the disparities and risks associated with these populations,” she added.

Therefore, Walters and colleagues aimed to understand oncology nurses’ knowledge, beliefs, and skills regarding LGBT patients to establish warranted training needs. They issued an online survey to 1253 health care professional at MSK, including 941 nurses, to evaluate LGBT healthcare knowledge, beliefs, communication behaviors, willingness to treat LGBT patients, behaviors encouraging LGBT disclosure, and perceived importance of LGBT sensitivity training.

The researchers included 7 items on knowledge adapted from published items; 12 items on beliefs adapted from the Sexual Orientation Beliefs Scale and Attitudes Toward Transgendered Individuals Scale, as well as published items; and 18 items on skills that were adapted from the Gay Affirmative Practice Scale, as well as quantitative and qualitative items added by the study team.

Notably, 81 survey participants identified as LGBT, and 810 (86.1%) said they had a friend or family member in the LGBT community.

In total, 86% of nurses surveyed had experience caring for individuals who identified as lesbian, gay, or bisexual, while 31% had experience with those who identified as transgender. However, only 4.7% of nurses were able to answer all knowledge items in the survey correctly, and about half identified 3 of the 7 answers correctly.

Higher knowledge scores appeared to be associated with favorable beliefs about sexual orientation and gender identity, favorable beliefs about LGBT healthcare, more open communication behaviors, greater encouragement regarding LGBT status disclosure, and greater perceived importance of LGBT sensitivity training.

The researchers noted these results are serving the foundation for the development of a communication skills training for nurses, and in the near future they will contribute to a mixed methods study comparing healthcare providers and LGBT patient preferences and perceptions regarding LGBT patient care.

“Across the board, we heard loud and clear from our nursing staff they want more training in this area,” Walters added.

Walters C, Banerjee S, Staley J, Haviland K. Nurses’ knowledge, beliefs, and skills toward LGBT patients. Presented at: Oncology Nursing Society 43rd Annual Congress; May 17-20, 2018; Washington DC. 

https://ons.confex.com/ons/2018/meetingapp.cgi/Paper/3718

A recent survey showed that nurses are willing to be trained in how to offer an affirmative healthcare experience to individuals who identify as lesbian, gay, bisexual, or transgender; however, only 4.7% were able to demonstrate knowledge of this patient community.

Nurses Show Interest in Learning About LGBT Patients With Cancer

Physical activity interventions should be individualized for adolescents and young adults (AYAs) with cancer, according to study findings presented at the Oncology Nursing Society 43

Of note, these interventions are needed during and after treatment, said Jeanne Erickson PhD, RN, University of Wisconsin-Milwaukee College of Nursing.

Despite the fact that cancer is the leading disease-related cause of death in AYAs, this group of individuals tends to be an understudied patient population. As a result, few studies have evaluated physical activity interventions in this population.

In addition, staying physically active has important short- and long-term benefits for patients with cancer, including reduced symptom severity, improved physical function, and better tolerance to treatment. However, AYAs tend to be less active during and after chemotherapy.

“Physical activity interventions are recommended to relieve symptoms and improve function,” Erickson said. “Few studies have explored symptoms and physical activity in AYAs during cancer treatment.”

Therefore, Erickson and colleagues are conducting the randomized PROMIS-29 trial which is designed to examine the effects of physical activity interventions for AYAs to help them self-manage fatigue. In her presentation, she described the symptoms and physical activity of young adults during the early months of chemotherapy to provide baseline data for the larger study.

Patients treated at the Froedtert Hospital/Medical College of Wisconsin Cancer Center and Children’s Hospital of Wisconsin who were aged 18 to 39 years and starting a chemotherapy regimen for any cancer diagnosis are eligible for the study.

To document their baseline physical activity, participants wore an accelerometer device for 7 days during chemotherapy administration to determine steps per day and the amount of time participants spent per day in light, moderate, and/or vigorous physical activity. In addition, symptom severity was surveyed on day 1 of a patient’s chemotherapy cycle.

The 21 AYAs were an average age of 33 years of age (range, 18-39 years); and majority were female (n = 15, 71%), white (n = 17; 81%), married (n = 12; 57.1%), and parents (n = 12; 57.1%). The AYAs were diagnosed with breast cancer (32%), lymphoma (31%), acute lymphocytic leukemia (25%), myeloma (6%), or melanoma (6%).

At baseline, the group averaged 4638 steps per day (range, 1318-11,572) with 233.35 minutes per day of light physical activity (range, 119-330), 16.08 minutes per day of moderate physical activity (range, 0.02-92), and no vigorous physical activity.

“These young adults were inactive during the early months of chemotherapy. We can measure that and compare that to an age-matched, national, healthy cohort. In that cohort, by average, young adults, males and females, had about 20 to 30 minutes of moderate physical activity a day, and this sample only had about 15,” said Erickson. “But there were various levels of physical activity in this sample. And their symptom scores were about average at the beginning of their chemotherapy regimen.”

For the PROMIS-29 profiling, a T score of 50 is considered average for the general US population, with a higher score being more of the concept, Erickson said. The mean standardized PROMIS-29 profile scores varied for physical function (49.48; range, 33.3-56.9), anxiety (56.33; range, 40.3-67.3), depression (52.27; range, 41-79.4), fatigue (55.86; range, 33.7-69.0), sleep disturbance (53.07; range, 37.5-66.0), ability to participate (49.56; range, 34.0-64.2), and pain interference (50.33; range, 37.3-64.2).

“It is interesting how their symptoms were about average,” Erickson said. “There is some evidence that, in particular, AYAs have higher symptom severity scores than other ages, but that didn’t look to be true in this beginning sample that I have. So, I will be interested to see how their related symptoms change over the months of treatment, and how that affects their physical activity.”

She is also interested to see what the AYA population impacted by chemotherapy treatment does with the remaining hours of their day, and how researchers can combat inactivity.

“If you think they had 4 hours of light physical activity, that means there about 20 hours filled with sedentary behavior and sleep,” Erickson said. “So how can we make sure we are looking more at their sleep and sedentary behavior, and prevent those minutes of inactivity?”

Lastly, Erickson noted she will continue to follow these patients for 8 months.

“It is important to look at how their physical activity changes during their months of cancer treatment,” she said. “The other concern is that they get caught in that cycle where they have fatigue and become less active and have more fatigue and become even more inactive. So, what I would like to see my intervention do is break that cycle of fatigue and try to maintain activity or prevent inactivity over the months of chemotherapy.”

Erickson J, Swartz A, Tokarek N. Physical Activity and Symptoms in Young Adults with Cancer in Early Months of Chemotherapy. Presented at: ONS 43rd Annual Congress; May 17-20, 2018; Washington D.C. 

https://ons.confex.com/ons/2018/meetingapp.cgi/Paper/3716

As part of a larger study, nurses found it is important for AYAs to remain physically active during and after cancer treatment.

Kristie Kahl

Articles

Patients with Unresectable Hepatocellular Carcinoma with Moderately Impaired Liver Function May Continue Lenvatinib Therapy

Adjuvant Chemo Does Not Improve Survival in Locally Advanced Cervical Cancer

Onboarding Reference Guide Aids APPs Treating Patients Receiving Bone Marrow Transplant

Nurses Show Interest in Learning About LGBT Patients With Cancer

Early Physical Activity Interventions Needed in Young Adults with Cancer