Selpercatinib (Retevmo) was recently approved for 2 new solid tumor indications. The kinase inhibitor was granted regular approval for locally advanced or metastatic 

 fusion–positive non–small cell lung cancer (NSCLC).

 It was also granted accelerated approval for patients with solid tumor harboring a 

Selpercatinib had previously received accelerated for 

-fused NSCLC approval based on initial findings from the phase 1/2 LIBRETTO-001 trial (NCT03157128). Confirmatory data from an additional 172 patients and 18 months of extended follow-up secured the agent’s full approval. Updated findings showed that patients with 

-positive NSCLC achieved a 61% overall response rate (ORR), a complete response rate (CR) 7.3% and a partial response (PR) rate of 54%. In addition, the median duration of response was 28.6 months (95% CI, 20–not estimable [NE]) and 63% achieved a response which lasted for 12 months or longer.

The accelerated approval was supported by findings from the phase 1/2 LIBRETTO-001 trial (NCT03157128), which showed that that the targeted therapy yielded an ORR of 44% (95% CI, 28%-60%) in patients with 

-fusion solid tumors, as well as a 4.9% complete response, and a 39% partial response rate. In this trial, the median duration of responses was 24.5 months (95% CI, 9.2-NE), and 67% of patients achieved a response that lasted for at least 6 months.

Patients who achieved responses included those with pancreatic adenocarcinoma, colorectal cancer, salivary, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma.

In terms of testing, in the population of patients with NSCLC, 94% of 

-fusions were identified with next-generation sequencing (NGS), 84.6% were confirmed with a tumor sample, 9.3% were found with a blood or plasma sample, 4.0% were detected with FISH, and 1.6% through PCR. In addition, 0.4% had their mutation tested through another method. In solid tumors, 97.6% of 

-fusions were detected via NGS, and 2.4% of these fusions were detected through FISH.

Selpercatinib comes in 40 mg and 80 mg capsules. For patients weighing less than 50 kg, the recommended dose is 120 mg twice a day. For those who are greater than 50 kg, the recommended dose is 160 mg twice a day. If a patient has severe hepatic impairment, they should receive a reduced dose.

Providers should avoid coadministering with acid-reducing agents, strong and moderate CYP3A inhibitors or inducers, CYP2C8 and CYP3A substrates, and certain P-gp substrates. If acid-reducing agents are necessary, then selpercatinib should be taken with food and the administration time should be modified. If strong or moderate CYP3A inhibitors cannot be avoided, the selpercatinib dose should be reduced. If a patient required CYP2C8 and CYP3A substrates, or P-gp substrates, the substrate dosages should be reduced, as recommended in their product labeling.

There are no contraindications, however, the agent comes with warnings for hepatotoxicity, interstitial lung disease (ILD), hypertension, hemorrhagic events, hypersensitivity, tumor lysis syndrome, hypothyroidism, and risk of impaired wound healing. The drug also increases the risk for embryo-fetal toxicities.

For hepatotoxicity risk, the label advice monitoring alanine aminotransferase (ALT) and aspartate aminotransferase (AST), prior to initiation selpercatinib and monitoring every 2 weeks during the first 3 months, followed by monthly monitoring as necessary.

Patients with uncontrolled hypertension should not initiate selpercatinib. All patients should have their blood pressure optimized prior to starting treatment and should be monitored at their first week of treatment and monthly thereafter. Thyroid function should also be assessed at baseline and periodically throughout treatment.

Patients should be evaluated for QT interval, electrolytes and thyroid stimulating hormone at baseline, and periodically throughout treatment. If patients require concomitant treatment with strong and moderate CYP3A inhibitors, minoring should be even more frequent.

Because selpercatinib increases the risk of impaired wound healing, it should be withheld for at least 7 days prior to elective surgery. Following major surgery, patients should not receive this agent for at least 2 weeks and until their wounds have adequately healed. The safety of agent resumption following wound healing complications are not yet established.

In addition, if a patient developed hypersensitivity, the agent should be withheld, and corticosteroids should be initiated. Upon resolution, treatment should be resumed at a reduce dose and increased by 1 dose level each week until the dose is the same as it was prior to the onset of the reaction. Once the target dose has been reached, tapering can begin.

Based on the severity of possible hepatotoxicity, ILD, hypertension, or QT interval prolongation, the agent should be withheld, dose reduced, or permanently; discontinued.

The most common any-grade adverse events associated with selpercatinib include edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common grade 3 or 4 laboratory abnormalities include decreased lymphocytes, increased ALT, increased AST, decreased sodium, and decreased calcium.

FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive non-small cell lung cancer. News release. FDA. September 21, 2022. Accessed September 21, 2022. 

FDA approves first therapy for patients with lung and thyroid cancers with a certain genetic mutation or fusion. News release. FDA. May 8, 2020. Accessed September 21, 2022. 

FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. News release. FDA. September 21, 2022. Accessed September 21, 2022. 

Retevmo. Prescribing information. Eli Lilly and Company; 2022. Accessed September 21, 2022. 

Articles

Selpercatinib was approved by the FDA for RET fusion–positive non–small cell lung cancer and locally advanced or metastatic RET fusion–positive solid tumors. 

Selpercatinib Is Approved for 2 RET Fusion–Positive Solid Tumors, Non–Small Cell Lung Cancer

Patients with unresectable hepatocellular carcinoma (HCC) who received frontline tislelizumab achieved both a clinically meaningful overall survival (OS) benefit and a higher objective response rate (ORR) than patients who received sorafenib (Nexavar), according to data from a final analysis presented at the 2022 European Society of Medical Oncology Congress.

The humanized IgG4 anti–PD-1 monoclonal antibody was administered as a monotherapy in these patients in the randomized phase 3 RATIONALE-301 (NCT03412773) study. A total of 674 patients randomized to either tislelizumab (n = 342) or sorafenib (n = 332).

Investigators found a noninferior median OS of 15.9 months (95% CI, 13.2-19.7, months) in the tislelizumab arm compared with 14.1 months (95% CI, 12.6-17.4, months) in the sorafenib arm (HR, 0.85; 95.003% CI, 0.712-1.019; 

 = .0398). However, OS superiority for tislelizumab compared with sorafenib was not met, but the study still reached its primary end point of OS noninferiority in the monotherapy vs sorafenib.

This OS benefit was also observed across all subgroups, according to Masatoshi Kudo, MD, PhD, a lead investigator of the study who presented the final analysis results at the 2022 ESMO Congress.

Key subgroups where OS favored tislelizumab included patients 65 years or older (HR, 0.76; 95% CI, 0.57-1.02), patients in which microvascular invasion and/or extrahepatic spread was absent (HR, 0.78; 95% CI, 0.56-1.07), patients with hepatitis C infection (HR, 0.64; 95% CI, 0.38-1.08), and female patients (HR, 0.62; 95% CI, 0.39-0.99).

“There are currently no single agent checkpoint inhibitors approved in this setting,” explained Kudo, professor and chairman in the Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, in his presentation when explaining the background of this study. “Tislelizumab is a monoclonal antibody, which has a hybrid binding affinity for [PD-1] and was specifically engineered to minimize FCy gamma receptor binding on macrophages. Tislelizumab monotherapy has progressively demonstrated durable responses and was generally well tolerated in patients with previously treated advanced HCC.”

This study randomized patients 1:1 to either 200 mg of intravenous tislelizumab given every 3 weeks or 400 mg of oral sorafenib given twice a day. Eligible patients had to have histologically confirmed HCC, were naïve to systemic therapy, Child-Pugh class A, an ECOG performance score of 1, and no tumor thrombus involving the main trunk of the portal vein or inferior vena cava. Patients remained on treatment until disease progression or intolerable toxicity.

According to Kudo, the study consisted of mostly Asian patients (excluding Japan) at 62.9% (n = 215) in the tislelizumab arm and 63.3% (n = 210) in the sorafenib arm. Patients from Japan on either the study drug or control drug made up 11.1% and 11.7% of patients, respectively, followed by 26.0% and 25.0% from the rest of the world. The median age of patients in each arm was comparable at 62 years of age (range, 25.0-86.0) in the tislelizumab arm and 60 years old (range, 23.0-86.0) in the sorafenib arm. Moreover, over 80% of patients in both arms were male, over 75% were Barcelona-Clinic Liver Cancer stage C at the time of enrollment, and over 70% of patients in both arms had a Child Pugh score of 5. Most patients also had hepatitis B across both arms at 59.4% in the tislelizumab arm and 62.0% in the control arm.

When assessing these patients for the continuation of durable responses tislelizumab was associated with a higher ORR of 14.3% (95% CI, 10.8%-18.5%) vs 5.4% (95% CI, 3.2%-8.4%) in the sorafenib arm. Moreover, there were 10 complete responses in the tislelizumab arm compared with 1 patient in the sorafenib arm. However, 139 patients in the sorafenib arm had stable disease compared with 94 in the study arm, whereas 169 patients in the study arm had progressive disease vs 121 in the sorafenib arm.

Median duration of response was also longer in the study arm responders (n = 49) at 36.1 months compared with 11 months in the sorafenib responders (n = 18). Of these patients 71.4% have an ongoing response with tislelizumab compared with 40.0% with sorafenib. Yet, when looking at the median progression-free survival between both groups sorafenib was longer at 3.6 months (95% CI, 2.2-4.1) compared with 2.2 months in the study arm (95% CI, 2.1-3.5) with a hazard ratio of 1.11 (95% CI, 0.92-1.33).

Treatment-emergent adverse events (TEAEs) and treatment related AEs at grade 3 or higher were less frequent with the study drug at 48.2% and 22.2%, respectively, compared to 65.4% and 53.4% in the sorafenib arm. This also led to fewer discontinuations and dose modifications in the study drug compared with sorafenib at 10.9% and 31.1% vs 18.5% and 64.8%, respectively. However, TEAEs leading to death were comparable at 4.4% in the tislelizumab arm and 5.2% in the sorafenib arm.

Grade 3 or greater incidences of increased aspartate aminotransferase and/or alanine transaminase, increased blood bilirubin, decreased platelet counts, and diarrhea were lower in the tislelizumab group, below 50%, compared with higher rates in the sorafenib arm. According to Kudo this was especially so in the hypertension group and only patients on sorafenib experienced grade 3 or greater palmar-plantar erythrodysesthesia.

“To conclude, single agent tislelizumab demonstrated a clinically meaningful anti-tumor benefit vs sorafenib with a favorable and manageable safety profile in this patient setting,” Kudo said. “We hope to provide further insights on these data at future medical meetings.”

Kudo M, Qin S, Meyer T, et al. Final analysis of RATIONALE-301: randomized, phase III study of tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. 

. 2022;33(suppl_7):S808-S869. doi:10.1016/annonc/annonc1089

Patients with hepatocellular carcinoma achieved a median overall survival of 15.9 months with tislelizumab and 14.1 months with sorafenib.

Tislelizumab Rivals Sorafenib in Improving OS in Unresectable Hepatocellular Carcinoma

Videos

A broad overview of the treatment armamentarium for patients receiving first- or second-line therapy for HER2+ gastric cancer.

First- and Second-Line Treatment Options for HER2+ Gastric Cancer

Focused discussion on the management of antibody drug conjugate–related adverse events in gastric cancer, with a focus on neutropenia. 

T-DXd in HER2+ Gastric Cancer: Managing Neutropenia and Other AEs 

An update from the DESTINY-Gastric02 trial (NCT04014075) found that patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who received fam-trastuzumab deruxtecan-nxki (Enhertu) who had already undergone treatment with a trastuzumab (Herceptin)-based regimen achieved promising response rates with the antibody-drug conjugate. 

At a median follow-up of 10.2 months (range, 0.7-22.1), the confirmed objective response rate (ORR) was 41.8% (95% CI, 30.8%-53.4%) among the 79 patients treated. Complete response was reported in 4 patients (5.1%) and partial response was reported in 29 patients (36.7%). The median duration of response was 8.1 months (95% CI, 5.9-not estimable). The disease control rate was maintained from the primary analysis at 81.0% (95% CI, 70.6%-89.0%).

“The primary results of DESTINY-Gastric02 were based on a data cutoff of April 9, 2021, and it demonstrated at the time a confirmed ORR of 38.0% [95% CI, 27.3%-49.5],” Geoffrey Y. Ku, MD, said in a presentation of the findings. The primary end point of confirmed ORR was met in the primary analysis.

He highlighted that compared with the previously reported data the clinical benefit of the agent was maintained. “Responses tended to be durable…and to occur quickly with a median time to response of 1.4 months [95% CI, 1.4-2.6].” Ku is a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in New York, New York.

Updated survival data showed that patients who received trastuzumab deruxtecan had a median overall survival of 12.1 months (95% CI, 9.4-15.4) and a median progression-free survival of 5.6 months (95% CI, 4.2-8.3).

“The safety profile remains generally consistent with the established profile of trastuzumab deruxtecan,” Ku said. The median treatment duration was 4.3 months (range, 0.7-22.1) and the most common treatment-emergent adverse events (TEAEs) were nausea (67.1%), vomiting (44.3%), and fatigue (41.8%).

Grade 3 or higher TEAEs were reported in 55.7% of patients and 30.4% were drug related. The rate of serious TEAEs was 41.8% with 12.7% being related to trastuzumab deruxtecan. Rates of TEAEs leading to drug discontinuation, dose reduction, or death were 19.0%, 21.5%, and 13.9%, respectively. Drug-related TEAEs that led to treatment discontinuation in 10 patients, dose reduction in 14 patients, and death in 2 patients. Both deaths were associated with adjudicated interstitial lung disease (ILD)/pneumonitis with 1 death occurring 171 days after drug initiation and the second after 353 days.

Grade 1 adjudicated drug-related ILD/pneumonitis occurred in 2 patients, grade 2 in 4 patients. The median time to onset was 80.5 days (range, 42-344) with a median duration of 36 days (range, 15-142).

Patient-reported outcomes were presented for the first time at the 2022 ESMO Congress and were assessed using the European Organization for Research and Treatment of Cancer 5-dimensional (EQ-5D) survey and the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) measure. Results were presented through cycle 7, which Ku noted was approximately 5 months into treatment. “These [data] correlate well with duration of treatment, which was 4.8 months, many patients were treated up through the first 7 cycles,” he said. “Based on patient-reported outcomes, quality of life did not worsen through cycle 7.”

DESTINY-Gastric02 was a nonrandomized study that enrolled patients with pathologically documented gastric or GEJ cancer who had centrally confirmed HER2-positive disease defined as immunohistochemistry (IHC) 3+ or IHC 2+/in situ hybridization–positive. Patients must have had disease progression on a trastuzumab-containing regimen and an ECOG performance status of 0 or 1. Participants received trastuzumab deruxtecan at 6.4 mg/kg intravenously once every 3 weeks.

Previously reported baseline characteristics for the 79 enrolled patients showed that the population had a median age of 60.7 years (range, 20.3-77.8) and a majority had an ECOG performance status of 1 (63.3%). HER2 expression was primary IHC 3+ (86.1%) with 12.7% having IHC 2+/ISH+ disease and 1.3% not evaluable. In terms of histology, 34.2% of patients had gastric cancer and 65.8% has GEJ.2 Most patients had 2 or more metastatic sites (93.7%). The median time since diagnosis was 14.2 moths (range, 3.6-88.5).

The trial was a confirmatory study initiated for Western patients following positive data from the phase 2 DESTINY-Gastric01 (NCT03329690), a randomized study which evaluated trastuzumab deruxtecan vs physician’s choice of chemotherapy in patients who had progressed on at least 2 prior regimens, including trastuzumab, a fluoropyrimidine- and a platinum-containing chemotherapy. The trial enrolled patients in Japan and South Korea. The results supported the 

for patients who had received a prior trastuzumab-containing regimen in January 2021.

DESTINY-Gastric04 (NCT04704934), a phase 3 trial has been initiated to compare comparing trastuzumab deruxtecan vs ramucirumab (Cyramza) plus paclitaxel in patients with HER2-positive gastric or GEJ cancer with progression on or after a trastuzumab-containing regimen.

Ku G, di Bartolomeo M, Smyth E, et al; DESTINY-Gastric02 Investigators. Updated analysis of DESTINY-Gastric02: A phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (Pts) with HER2-positive (HER2+) unresectable/metastatic gastric/gastroesophageal junction (GEJ) cancer who progressed on or after trastuzumab-containing regimen. Presented at: European Society for Medical Oncology Congress 2022; September 9-13, 2022; Paris, France.

van Cutsem E, di Bartolomeo M, Smyth E, et al. Primary analysis of a phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (Pts) with HER2-positive (HER2+) unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer who progressed on or after a trastuzumab-containing regimen. 

. 2021;32(suppl 5):S1332. doi:10.1016/j.annonc.2021.08.2135

FDA approves fam-trastuzumab deruxtecan-nxki for HER2-positive gastric adenocarcinomas. FDA. January 15, 2021. Accessed September 10, 2022. bit.ly/3qttyss

After 10 months of follow-up, the confirmed objective response rate among patients with metastatic gastric cancer or gastroesophageal junction adenocarcinoma who received trastuzumab deruxtecan was 41.8%. 

Trastuzumab Deruxtecan Continues to Elicit Encouraging Responses in Patients With Metastatic Gastric/GEJ Cancer

Cannabinoids are becoming more popular for patients with cancer as a pain management strategy. However, with inconsistent laws across states and federal bodies, it can be difficult for nurses and patients to comfortably discuss cannabinoids and cannabinoid use.

As the public perception and patient success stories with unconventional, alternative, and natural therapeutics shift consumer attitudes, it is important for nurses and their patients to understand the differences in the products and the adverse effects associated with each. According to a study by Butler et al in 2021, nearly half of individuals who participated in a survey who had consumed cannabidiol (CBD) did not disclose use to their health care provider.

“We see a lot of patients who have been trying to talk to us about CBD [cannabidiol], and cannabinoids and THC, [tetrahydrocannabinol]” Karen Hande, PhD(c), DNP, ANP-BC, CNE, FAANP, ANEF, a professor of nursing at Vanderbilt University School of Nursing, said in a presentation during the Oncology Nursing Society Bridge.

Although Hande stated in her presentation that she was no expert in cannabinoids or medical cannabis, her clinical research primarily focuses on helping patients effectively manage their cancer-related pain. Therefore, she has become very interested in cannabis and has dedicated a lot of time and research to best understand the evidence-based data that exists for these products. In her presentation, “Cannabinoids for Patients With Cancer,” Hande discussed the available evidence on CBD and the possible risks, particularly in vulnerable populations.

“I think it’s just important for under us to understand a kind of broad overview about cannabinoids and THC and CBD, because this gives us a better understanding of where the laws come into play,” Hande said. She added, “It took me quite some time to try to understand all the differences and trying to make sure I give the correct information to my patients.”

A key concept for oncology nurses to understand, according to Hande, is the variations of cannabinoids.

Cannabinoids are compounds found in the cannabis plant. These compounds interact with the human endocannabinoid system. The exact relationship still required further understanding.

“Cannabis has many names for [many] strains, and hemp and marijuana are under this big umbrella of cannabis plants; they are all considered to be 1 species: the cannabis sativa plant,” she said. “This is a genus of flowering plants. And these can contain about over 100 phytocannabinoids, [and] they have a wide range of effects on the body in the brain.”

The following products are derived from cannabis: marijuana, hemp, THC, and CBD. In addition, there are man-made synthetic cannabinoids (K2/Spice); however, these agents are designed to mimic the mind-altering effects of illicit drugs. For her talk, Hande chose to focus on the products derived from the plant itself, as oncology nurses are more likely to encounter patients using plant-derived products.

If a patient reports marijuana use, this means they are using the dried flowers, leaves, stems, and seeds of the cannabis plant. Marijuana is also known as cannabis, weed, pot, or dope. Specifically, it can be defined as a plant with at least 0.3% delta-9 THC by weight. It is consumed by smoking (joints, blunts, bongs), vaping (vaporizing electronics devices), or by mixing or infusing it into foods or drinks (edibles).

“This is an important differentiating factor that I’ll be highlighting regularly through this talk,” Hande said during her presentation. “Marijuana is more than 0.3% of THC by weight.”

Marijuana is the most used federally illegal drug in the United States, with approximately 18% of Americans reported using it at least once in 2019 (~48.2 million Americans).1

Because marijuana has THC, it is associated with the following health risks: alterations in memory, learning, attention, decision-making, coordination, emotion, and reaction times.2 In terms of long-term health, marijuana has been linked to an increased risk of psychosis and schizophrenia,3 and, like other drugs, it’s use during pregnancy may increase the risk of embryo-toxicities.4 Moreover, this drug, depending on where it is sourced, may be laced with other substances. Consumers may or may not be aware of other substances in their product.

Using marijuana in combination with other agents may also result in impairment and can increase the risk of overdose.

Federally, marijuana is illegal as a recreational drug. It is classified as a schedule 1 drug, per the Drug Enforcement Agency. Although it is legal in some states for medical for nonmedical adult use, this does not mean that is safe, Hande noted. Specifically, smoking marijuana can expose users to harmful chemicals, and insufficient evidence exists to document the safest method for consuming.

Legally, hemp must contain a THC concentration of less than 0.3% by dry wright. It is the same species of plant as the cannabis plant and, along with bamboo, it is one of the fastest growing plants on Earth. There are almost no restrictions on hundreds of compounds made by the plant. Industrial hemp is cannabis sativa plant grown specifically for industrial or medicinal use.

“Many states across the country have hemp cultivation,” Hande said. “This allows cultivation of hemp from commercial or research or pilot programs. There are only a few states that do not allow cultivation of hemp.”

In 2018, the farm bill legalized the production and sale of hemp and its extracts, removing the product from the controlled substance act. Of note, per federal law, hemp cannot contain greater than 0.3% THC. If the concentration of THC surpasses this measurement, it is classified as marijuana.

As of September 2022, 47 states have enacted legislation to establish hemp production programs or cultivation research.

THC is a compound of the cannabis plant. This psychoactive agent causes, what is known as a high. It is consumed via dabbing—a specific method for inhaling THC concentrates.

Unfortunately, the concentrated forms of THC mean that there is an increased risk of additives or contaminating substances existing in the product.

CBD is another active cannabinoid found in the cannabis plant. This agent is not psychoactive and consequently does not cause a high.

CBD can be derived either directly from the cannabis plant or from a hemp product. The key difference between cannabis- and hemp-derived CBD is the concentration of THC. Hemp-derived CBD must have a THC concentration less than 0.3% to be federally legal. CBD products containing greater concentrations are federally illegal but are legal under some states.

“The main difference between cannabis and hemp-derived CBD is the amount of THC that it can contain,” Hande stressed. “Hemp-derived CBD includes less than 0.3% of the THC. [Therefore,] it’s federally legal to use hemp-derived CBD, but CBD products that contain more than 0.3% of THC are federally illegal. This is where the conflict between the state and the federal laws [can arise].”

The extraction process for CBD and THC are similar; farmers harvest the hemp and it is sent to an extractor. If the extraction is not performed with pharmaceutical grade standards, the CBD may become contaminated with THC, chemical solvents, or even pesticides. This is compounded by the fact that the US does not hold CBD supplies to a standard, and federal enforcement is lacking.

CBD can be converted into delta-8-THC, delta-9 THC, and other THC isomers through a solvent, acid, and heat. These products end up with higher concentrations of delta-8 THC than those which occur naturally in the cannabis plant. Consequently, these products may create harmful by-products that presently are not well-characterized.

Delta-8 THC products are increasing in popularity, in both marijuana- and hemp-based markets. It is appearing in markets that are operating legally under state, territorial, or tribal laws.

As of 2022, most states and territories permit full and restricted marketplaces where consumers can purchase hemp and hemp-derived CBD products.

According to Hande, there are a wide variety of delta-8 THC-containing products in the market. For example, vapes, smokable hemp sprayed with delta-8 THC extract, distillates, tinctures, gummies, chocolates, and even infused beverages can fit into this category. Moreover, the testing method for these products are still under development. This means that Delta-8 THC products may not be systematically tested for contaminants such as heavy metals, solvents, or pesticides which can cause adverse health effects.

How to Talk to Your Patient About Cannabinoid Use

Nurses hold a key role in discussing not only the risks of cannabinoid use but providing educational information for the safe consumption. Should a patient be interested in trying CBD products, counsel on the lack of evidence, contaminants, misleading labels, and legal issues of surrounding use. One approach to counter the “buyer beware” notion is to provide evidence-based patient education and to screen for any drug/drug interactions that may occur should the patient consume CBD products.

Additionally, assessing the patient’s baseline knowledge base before use will be beneficial and open communication may help establish trust and increase reported use between the patient and the health care provider. Finally, addressing the topic early on in care may remove the barrier of the stigma surrounding cannabinoid use.

Hande concluded by adding that many trials are ongoing in the cannabinoid arena and that results are expected to be published over the next several years. She noted that the oncology nurses should be up-to-date on the latest findings to provide guidance.

Marijuana and public health data and statistics. Centers for Disease Control and Prevention. June 8, 2021. Accessed September 14, 2022. bit.ly/3ROqaoi

Testai FD, Gorelick PB, Aparicio HJ, et al. Use of marijuana: effect on brain health: a scientific statement from the American Heart Association. 

. 2022;53(4):e176-e187. doi:10.1161/STR.0000000000000396

Di Forti M, Quattrone D, Freeman TP, et al. The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study. 

. 2019;6(5):427-436. doi:10.1016/S2215-0366(19)30048-3

Health effects of marijuana and cannabis-derived products presented in new report. National Academies. January 12, 2017. Accessed September 14, 2022. 

Karen Hande, PhD(c), DNP, ANP-BC, CNE, FAANP, ANEF, explains the difference between some of the popular cannabinoid products that patients with cancer may be taking.

Oncology Nurses: What Cannabinoid Is Your Patient Taking?

A multicentre, retrospective study showed that treatment-related adverse effects (TRAEs) associated with atezolizumab (Tecentriq) plus bevacizumab (Avastin) were prognostic of improvements in survival outcomes in patients with hepatocellular carcinoma (HCC). Findings were presented at the 16th Annual International Liver Cancer Association Conference Annual Conference.

Investigators concluded that the significant improvement in overall survival (OS) and progression-free survival (PFS) occurred in patients treated with atezolizumab plus bevacizumab associated with the development of any atezolizumab-related AE and hypertension as well as proteinuria from bevacizumab. Although more prospective studies are needed to further investigate and validate these findings, in a biomarker-deprived context, TRAEs can serve as potential predictors of prognosis.

Specifically, TRAEs were correlated with improved overall survival (OS) and progression-free survival (PFS) outcomes according to Cox proportional-hazards regression models. A total of 371 patients were eligible for inclusion in the analysis. Any-grade TRAEs were reported for 67% of patients and grade 3 to 5 TRAEs were recorded in 21% of patients.

For atezolizumab, 44% of patients experienced any grade of TRAEs, 9% of which were grade 3 to 5 events. Bevacizumab-related TRAEs were reported in 47% of patients and 14% were grade 2 to 5 events.

For PFS, the HR for patients who experienced an atezolizumab-related AE of any grade vs those who did not was 0.50 (95% CI, 0.36-0.69

 < .001). The HR for grade 3 to 5 events was 0.66 (95% CI, 0.34-1.27

Patients who had bevacizumab-related TRAEs vs those who did not the HR was 0.59 (95% CI, 0.44-0.80; 

 = .003) for grade 3 to 5 TRAEs. HRs for bevacizumab any-grade TRAEs were as follows: hypertension, 0.52 (95% CI, 0.37-0.74; 

 < .001), proteinuria, 0.48 (95% CI, 0.34-0.68; 

 < .001), and thrombosis/bleeding, 0.88 (95% CI, 0.59-1.32; 

The HR for OS among patients with any-grade TRAEs treated with atezolizumab vs those who had no TRAEs was 0.62 (95% CI, 0.40-0.95; 

 = .04) for any-grade bevacizumab-related TRAEs.

The HRs for PFS for patients who received bevacizumab and had any-grade AEs were as follows:

Thrombosis and bleeding, 1.17 (95% CI, 0.70-1.95; 

The OS HRs for patients who had grade 3 to 5 TRAEs vs those who have not were 1.02 (95% CI, 0.43-2.41; 

 = .97) for atezolizumab and 0.80 (95% CI, 0.46-1.40; 

The HRs for OS for patients who received bevacizumab and had grade 3 to 5 AEs were as follows:

Thrombosis and bleeding, 1.67 (95% CI, 0.91-3.06; 

In the analysis, most eligible patients were men (84%) with a median age of 66 years. Patients were excluded if they had previous systemic treatments or Child-Pugh C status. Data were collected from 2019 to 2021 and came from 14 centers in Europe (n = 11), the US (n = 86), and Asia (n = 236).

The most common cause of disease was chronic viral hepatitis 64%. In terms of disease status, 72% of patients had Barcelona Clinic Liver Cancer disease and 80% had Child-Pugh A disease status and 20% of patients had Child-Pugh B status.

HCC is a leading cause of cancer death around the world and the standard of care for over 10 years was first-line sorafenib (Nexavar), which had historic median OS of 10 to 12 months in phase 3 studies. Atezolizumab plus bevacizumab was approved May 29, 2020, for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy based on the global, open-label phase 3 trial IMbrave150 (NCT03434379).2,3

In the trial, patients received atezolizumab plus bevacizumab (n = 336) or sorafenib (n = 165) from March 15, 2018, to January 30, 2019.Per RECIST 1.1 criteria the overall response rate (ORR) was 28% in the atezolizumab plus bevacizumab group vs 12% in the sorafenib group. The estimated median PFS was 6.8 months (95% CI, 5.8-8.3) vs. 4.3 months (95% CI, 4.0-5.6), respectively (HR, 0.59; 95% CI, 0.47-0.76; 

Updates from the trial performed 12 months after the primary analysis showed a 5.8 month longer median OS with atezolizumab plus bevacizumab vs sorafenib. The ORR was 30% with the doublet with a median duration of response of 18.1 months. After a median follow-up of 15.6 months (range, 0-28.6), the median OS was 19.2 months (95% CI, 17.0-23.7) with atezolizumab plus bevacizumab and 13.4 months (95% CI, 11.4-16.9) with sorafenib (HR, 0.66; 95% CI, 0.52-0.85; descriptive 

 < .001). At 12 and 18 months, respectively, survival rates were 67% and 52% in the atezolizumab plus bevacizumab group and 56% and 40% patients in the sorafenib arm.

IMbrave150 data showed grade 3/4 TRAEs occurred in 43% of safety evaluable patients (n = 329) in the atezolizumab plus bevacizumab group and 46% of safety evaluable patients (n = 156) in the sorafenib arm.

D’Alessio A, Cheon J, Fulgenzi CAM, et all. Treatment-related adverse events and improved survival with atezolizumab plus bevacizumab; a global, real-world study. Poster presented at: 16th Annual International Liver Cancer Association Conference; September 1-4, 2022; Madrid, Spain. Accessed September 7, 2022. 

Casak SJ, Donoghue M, Fashoyin-Aje L, et al. FDA approval summary: atezolizumab plus bevacizumab for the treatment of patients with advanced unresectable or metastatic hepatocellular carcinoma. 

. 2021;27(7):1836-1841. doi:10.1158/1078-0432.CCR-20-3407

Cheng AL, Qin S, Ikeda M, et all. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. 

. 2022;76(4)862-873. doi:10.1016/j.jhep.2021.11.030

A multicentre, retrospective study showed that treatment-related adverse effects associated with atezolizumab plus bevacizumab were prognostic of improvements in survival outcomes in patients with hepatocellular carcinoma.

Real-World Data Show TRAEs Associated With Improved Survival With Atezolizumab plus Bevacizumab in HCC

® spoke with Christine Miaskowski, PhD, RN

professor in the Department of Physiological Nursing and Anesthesia at UCSF School of Nursing. Miaskowski discusses results from research which showcases an increased risk of hearing loss among patients who received platinum- or taxane-based cancer treatments. She also discusses the importance of including hearing assessments as a standard of care for survivors.

Top takeaways from the discussion include:

“When we did audio metrically confirmed hearing loss [assessments], we found that between 50% to 70% of survivors had confirmed hearing loss.” 

“It’s really, very surprising because it is a group of patients with very common cancers: breast, lung, gynecologic and GI [gastrointestinal] malignancies.” 

“The good news is that the type of hearing loss these patients experience is amenable to a hearing aid. So, if we can get people tested, and they demonstrate this kind of hearing loss, we can improve their quality of life.” 

“Nurses care about interactions with other people, people’s quality of life, [their] social function… if you've got hearing loss, and you're sitting at a table with people, and you can't hear them, you're not going to be likely to participate.” 

“We don’t even think about [some of] these consequences; in terms of occupation, social gatherings, safety for a child… We really, as nurses, need to be doing something about this.” 

Episode 33: Balancing the Benefit and Toxicity of Cisplatin in Young Children with Cancer

Episode 45: Key Advances in Cancer Survivorship Toxicity Management

Audiological Assessments May Be Vital Component of Cancer Survivorship Care Following Chemotherapy

Hearing Loss Found in Testicular Cancer Survivors After Cisplatin Therapy

Genetic Mutation Could Play Role in Cisplatin-Induced Hearing Loss

Oncology Nursing News® Publication Features

Survivors Need Research-Based Interventions and Stronger Coordination Across Care Continuum

What Are the Needs of Cancer Survivors 5 Years or More After Treatment?

Everyone's Business: Taking Survivorship Care to the Next Level

Heather E. Wheeler Discusses Cisplatin-Induced Hearing Loss

Cheung S, Henderson-Sabes J, Mastick J, et al. Cancer survivors and neurotoxic chemotherapy: hearing loss and tinnitus. 

. Published online July 27, 2022. doi:10.1136/spcare-2022-003684

Romano A, Capozza MA, Mastrangelo S, et al. Assessment and management of platinum-related ototoxicity in children treated for cancer. 

2020;12(5):1266. doi:10.3390/cancers12051266

Biro K, Noszek L, Prekopp P, et al. Characteristics and risk factors of cisplatin-induced ototoxicity in testicular cancer patients detected by distortion product otoacoustic emission. 

. 2006;70(3):177-184. doi:10.1159/000093776

Cheraghi S, Nikoofar P, Fadavi P, et al. Short-term cohort study on sensorineural hearing changes in head and neck radiotherapy

2015;32(7):200. doi:10.1007/s12032-015-0646-3

Langer T, am Zehnhoff-Dinnesen A, Radtke S, Meitert J, Zolk O. Understanding platinum-induced ototoxicity. 

. 2013;34(8):458-469. doi:10.1016/j.tips.2013.05.006

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

Thanks again for listening to 

Podcasts

In this episode of “The Vitals,” Christine Miaskowski, PhD, RN, discusses research showcasing that adult patients receiving either a platinum-based chemotherapy, taxane alone, or a combined regimen of platinum- and taxane-based treatment may be at risk of hearing loss. 

Are Hearing Tests Necessary For Adult Cancer Survivors?

In an updated network meta-analyses (NMA) of patients with relapsed or refractory metastatic colorectal cancer (mCRC), dose optimization of regorafenib (Stivarga) improved survival outcomes vs best supportive care, fruquintinib (Elunate), standard-dose regorafenib, and trifluridine/tipiracil (Lonsurf). Results from the updated NMA were presented at the 2022 

European Society for Medical Oncology Congress.

Regorafenib dose optimization was defined as 80 mg daily for week 1, 120 mg daily for week 2 and 160 mg daily for week 3 onward. The median overall survival (OS) for patients treated with on this schedule was 9.8 months (95% CI, 7.5-11.9). Comparatively, the median OS for patients who received best supportive care, regorafenib standard dosing (160 mg), trifluridine/tipiracil, and fruquintinib was 6.4 months (95% CI, 2.3-11.1), 7.5 months (95% CI, 4.6-11.9), 7.5 months (95% CI, 4.2-12.6), and 7.7 months (95% CI, 4.2-13.5), respectively.

Regorafenib dose optimization provided a reduction in the risk of death of 52% (HR, 0.48; 95% CI, 0.28-0.82), 28% (HR, 0.72; 95% CI, 0.41-1.27), 31% (HR, 0.69; 95% CI, 0.40-1.20), and 26% (HR, 0.74; 95% CI, 0.41-1.33) vs each comparator, respectively.

Regorafenib dose optimization also led to an improvement in progression-free survival (PFS) in all groups except fruquintinib. The median PFS among patients treated with regorafenib dose optimization was 2.8 months (95% CI, 2.0-2.5). Patients who received best supportive care, regorafenib standard dosing, and trifluridine/tipiracil achieved a median PFS of 1.9 months (95% CI, 1.0-2.5), 2.1 months (95% CI, 1.7-5.9), and 2.0 months (95% CI, 1.8-5.8), respectively.

The hazard ratios compared with regorafenib dose optimization, were 0.34 with best supportive care (95% CI, 0.19-0.61), 0.84 with regorafenib standard dosing (95% CI, 0.47-1.48), and 0.74 with trifluridine/tipiracil (95% CI, 0.40-1.35) all did not lead to a PFS benefit.

The median PFS in the fruquintinib was 3.9 months (95% CI, 2.0-10.3), surpassing that achieved with regorafenib dose optimization (HR, 1.29; 95% CI, 0.68-2.45).

Investigators concluded that regorafenib dose optimization may represent a favorable treatment option for patients with mCRC.

In February 2022, investigators conducted a systematic literature review which identified randomized controlled trials to include in the NMA and a feasibility assessment was conducted. The NMA included 3 global or US-only trials—ReDOS (NCT02368886), CORRECT (NCT01103323), and RECOURSE (NCT01607957—and 4 Asia-only trials (TERRA (NCT01955837), a phase 2 trial (JapicCTI-090880), CONCUR (NCT01584830), and FRESCO (NCT02314819).

The standard dosing for oral regorafenib is 160 mg daily for the first 21 days of each 28-day cycle. The label notes that dose modifications should occur in 40 mg increments, with the lowest recommended daily dose being 80 mg. Reductions to 120 mg are included for the following occurrences: grade 2 hand-foot skin reaction, after recovery of any grade 3/4 adverse reaction except infection, for grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation. Reductions to 80 mg are recommended for the following: re-occurrence of grade 2 hand-foot skin reaction at the 120-mg dose, or after recovery of any grade 3/4 adverse reaction at the 120 mg dose (except hepatotoxicity or infection).

At the optimized-dose level, the agent displayed no significant drug-related adverse events (AEs) over a standard-dose strategy of 21 days per 28-day cycle.1 The dose optimization strategy aims to lower incidences of AEs and allow patients to receive comparable treatment with the agent.

In the NMA, the most common grade 3 or greater AEs were neutropenia, leukopenia, anemia, hand-foot skin reaction, fatigue, and hypertension.1 Regorafenib dose optimization led to lower hematological toxicities vs trifluridine/tipiracil. The lowest number of grade 3 or higher drug-related AEs were in the best supportive care group; however, safety events varied significantly as some studies reported AEs as drug-related while others reported them as treatment-emergent.

Significant AEs included increased aspartate transaminase, diarrhea, febrile neutropenia, and death.

Additionally, findings were consistent across fixed effect (FE) and random effect (RE) Bayesian and FE and RE frequentist Bucher NMAs which were used to synthesize the HRs for OS and PFS. The Bucher RE NMAs HRs were applied to the regorafenib dose optimization Kaplan-Meier curves from the ReDOS trial to approximate the predicted median OS and PFS of each treatment.

Burnett H, Proskorovsky I, Yoon S, et al. Impact of regorafenib dose optimization on comparative outcomes in the treatment of relapsed/refractory metastatic colorectal cancer. Poster presented at: 2022 European Society for Medical Oncology; September 9-13, 2022; Paris, France. Accessed September 12, 2022.

Stivarga. Prescribing information. Bayer HealthCare Pharmaceuticals Inc; 2020. Accessed September 13, 2022. bit.ly/3eGtPFL

Bekaii-Saab TS, Ou FS, Ahn DH, et al. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study. 

. 2019;20(8):1070-1082. doi:10.1016/S1470-2045(19)30272-4

Patients with relapsed or refractory metastatic colorectal cancer who received dose-optimized regorafenib achieved superior survival outcomes than those who received best supportive care, fruquintinib, standard-dose regorafenib, and trifluridine/tipiracil. 

Dose-Optimized Regorafenib Provides Comparable, Safe Option for mCRC

Before closing out their discussion on antibody drug conjugate use in breast cancer management, panelists consider ongoing clinical trials in this setting. 

Gastrointestinal Cancer