Last month, 2 targeted therapies were added to the fold of FDA approved non–small cell lung cancer (NSCLC) treatments. 

 for patients with metastatic disease whose tumors harbor a 

fam-trastuzumab deruxtecan-nxki (Enhertu) was approved

-mutated unresectable or metastatic NSCLC.

“For patients with metastatic NSCLC, the goal of systemic therapy is to live as well as possible for as long as possible,” Kelly Goodwin, MSN, RN, ANP-BC said. "A better understanding of the molecular pathways that contribute to NSCLC has led to the development of targeted therapies that have helped to improve survival rates and decrease treatment-related toxicities for certain subsets of patients with NSCLC.”

 Goodwin, a nurse practitioner with the Mass General Cancer Center's Thoracic Oncology Team, highlighted how the approvals of these 2 targeted therapies are continuing to expand options for patients with NSCLC, and what nurses who are caring for these patients should know about their safety profiles.

Capmatinib for MET exon skipping 14 NSCLC

The regulatory decision to grant capmatinib full approval was supported from findings from the phase 3 GEOMETRY mono-1 trial (NCT02414139). Findings from this trial demonstrated that patients with 

 exon 14 skipping mutations who received capmatinib experienced promising overall responses.

“In GEOMETRY mono-1, patients with MET exon 14 skipping mutations and MET gene amplifications [who] received capmatinib [had] meaningful responses and an acceptable safety profile across all cohorts,” Goodwin said. “Patients who received capmatinib as the first line of therapy achieved a median OS [overall survival] of 20.8 months, overall response rate [ORR] of 67.9%, median duration of response [DOR] of 12.6 months, and a median progression-free survival [PFS] of 12.4 months. [In comparison, these patients achieved] an OS of 13.6 months, an ORR of 40.6%, a median DOR of 9.7 months, and a median PFS of 5.4 months if used in the second or third-line setting.”

According to Goodwin, this approval may be especially beneficial for patients who identify as nonsmokers.

“Research has shown that cancer promoting mutations can be found across all lung cancer histologies and smoking histories,” she said. “[However], 

 exon 14 skipping mutations are more frequently identified in patients with nonsquamous tumor histology, older patients, and females who are less likely to be nonsmokers. 

gene amplifications are found in approximately 2% to 4% of NSCLCs through RNA based NGS [next-generation sequencing] testing.”

Tepotinib (Tepmetko) is also approved for the same indication but, unlike capmatinib, has not been granted full approval. The accelerated approval was supported by findings from the phase 2 VISION trial (NCT02864992), which showed that patients with 

 exon 14 skipping who received tepotinib achieved an ORR of 43% and a median DOR of 11.1 months (95% CI, 9.5-18.5).

According to Goodwin, it is exciting to have 2 approved targeted therapies on the market for this subtype.

“Tepotinib received FDA approval for the treatment of metastatic NSCLC harboring a 

 exon 14 skipping mutations less than 1 year after the approval of capmatinib—marking an exciting time for patients, caregivers and providers,” she said.

The 2 agents have demonstrated comparable efficacy thus far, although capmatinib may be preferred in the frontline.

“Overall response rates and DORs were similar across lines of therapy in patients in patients receiving tepotinib, [although] there appears to be a significant benefit to frontline capmatinib,” Goodwin said.

In terms of safety, the drugs are similar, she added. Although myalgias have been reported with tepotinib, overall, peripheral edema, gastrointestinal toxicity, fatigue, appetite changes, and dyspnea are common in patients treated with either MET inhibitor. Moreover, potentially life-threatening interstitial lung disease (ILD)/pneumonitis and transaminitis have been observed in patients treated with both agents.

Goodwin noted that several factors can influence treatment recommendations, including factors such as functional status, symptom or disease burden, and pre-existing comorbidities. A patient’s ability or willingness to adhere to treatment, as well as their medication coverage with insurance, are factored into decision-making as well. In her own practice, she has noticed that capmatinib is being offered more consistently, however, she acknowledges that this agent has been available for longer.

“In my own practice I have seen capmatinib used more regularly and I think this is partly a reflection of the drug being first to market—providers look at efficacy, safety and cost closely when making a decision to integrate later approvals into the practice,” Goodwin said, noting that many of the patient education points are similar with the 2 MET inhibitors.

“Regardless of drug selection, it is important to ask patients to call immediately with sudden changes in their breathing including new or worsening shortness of breath, a persistent cough, chest tightness or wheezing, given the risk of ILD/pneumonitis,” she continued. “Patients should also be encouraged to call with poorly controlled nausea, vomiting or bowel changes associated with lightheadedness, weakness or weight loss, given the risk of renal dysfunction.”

Moreover, nurses and patients should be aware peripheral edema is a common adverse effect of MET inhibitors, meaning that patient should be encouraged to call if any asymmetric peripheral edema, calf pain, skin changes or fevers, as these may be indicative of greater venous thromboembolism risk. Similarly, patients who are receiving MET inhibitors benefit from multidisciplinary care. Goodwin recommended referring these patients to a nutritionist to optimize their care and proactively manage treatment-related edema risk.

The approval of trastuzumab deruxtecan marks the first HER2-directed targeted therapy available for patients with NSCLC.

 According to Goodwin, this approval is changing the dynamic of how patients with this disease are being treated.

“The approval of trastuzumab deruxtecan is revolutionary—bringing more effective, safer targeted therapies to a growing number of patients living with NSCLC,” she said. “With more comprehensive biomarker testing and safer, more effective, therapies our patients are living longer.”

This approval was supported by data from the phase 2 DESTINY-Lung02 (NCT04644237). The trial showed that patients with advanced HER2-mutant NSCLC derived durable clinical benefit from the antibody-drug conjugate.The median ORR was 57.7% (95% CI, 43.2%-71.3%); the median PFS was 8.2 months, and the median overall survival was 17.8 months. Data surrounding central nervous system (CNS) activity is not yet mature.

“Many patients with metastatic lung cancer are found to have CNS metastasis at initial diagnosis or later in their treatment course,” Goodwin explained. “Review of the data DESTINY- Lung02 data indicates CNS responses with trastuzumab deruxtecan, but routine screening and surveillance was not required on study,” she added. “I am eager to see the final data around CNS activity and to see if there are differences in safety and efficacy in the 2 doses being studied.”

In terms of safety, no new signals were reported in the DESTINY-Lung02 trial. Yet, Goodwin still advises solid monitoring throughout a patient’s first few cycles.

“The drug is given IV [intravenously] every 3 weeks, but I encourage patients to be seen weekly during the first cycle or 2 of therapy for laboratory monitoring and symptom management,” she said. “As trastuzumab deruxtecan is approved in the second-line setting and beyond, patients may be experiencing more disease related symptoms at the time of treatment initiation and may have borderline bone marrow function.”

Moreover, trastuzumab deruxtecan carries boxed warnings for potentially fatal ILD, neutropenia, and left ventricular dysfunction.”

According to Goodwin, patients should be encouraged to call the office immediately for sudden respiratory changes including dyspnea, cough, wheezing, chest tightness or pain, fluid retention/weight gain or fevers/signs of infection.

“I recommend patients have a thermometer, scale, and pulse oximeter at home, if possible,” she said. “[In addition], all patients should undergo a baseline echocardiogram before starting therapy and every 3 months while on therapy or sooner as clinically indicated. If a patient has underlying cardiac disease, it is important to engage cardiology for any changes in clinical condition. Patients with respiratory changes should undergo in-person evaluation with resting and ambulatory oxygen saturation monitoring and high-resolution CT scans.”

Any dizziness or palpitations should be reported right away, she added.

She shared that dose delays and reductions, as well as the use of growth factors or blood products, can be employed help patients who are experiencing side effects related to therapy. However, patients who develop radiographic or symptomatic pneumonitis that is worse than grade 1 should not be rechallenged.

FDA approves capmatinib for metastatic non-small cell lung cancer. FDA. Updated August 11, 2022. Accessed September 13, 2022. 

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capmatinib-metastatic-non-small-cell-lung-cancer

FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer. FDA. Updated August 16, 2022. Accessed September 13, 2022. 

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-her2-mutant-non-small-cell-lung

Tabrecta. Prescribing information. Novartis Pharmaceuticals Corporation; 2022. Accessed September 13, 2022. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213591s004lbl.pdf

Tepmetko. Prescribing information. EMD Serono Inc; 2021. Accessed September 13, 2022. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214096s000lbl.pdf

Enhertu. Prescribing information. Daiichi Sankyo Inc; 2022. Accessed September 13, 2022. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761139s021lbl.pdf

Articles

Kelly Goodwin, MSN, RN, ANP-BC, discusses the significance of the recent FDA approvals of capmatinib and trastuzumab deruxtecan for patients with non–small cell lung cancer.

Goodwin Provides Nursing Perspective on Recent FDA Approvals in NSCLC

Most adolescent or young adults with advanced cancer prefer to die at home, according to results of a qualitative interview study published in 

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

“Our data suggest a preference for home death for most AYAs with advanced cancer,” wrote Oreofe O Odejide, MD, assistant professor of medicine and medical oncology at the Dana-Farber Cancer Institute, and co–investigators.

“Unfortunately, this preference is aspirational for many, as the majority die in hospital settings. To ensure that the EOL [end-of-life] experiences of AYAs align with their preferences, robust home-based services for symptom control and logistical/psychosocial support for family caregivers and siblings are imperative: we need innovative strategies that close the gap between preferred and actual location of death to achieve high-quality EOL care for AYAs with cancer.”

In the US, more than 9000 AYA patients die of cancer every year, and existing data suggests that EOL care for may be less than optimal in this population. High-intensity care, frequent hospitalizations, intensive care unit admission, and chemotherapy in the last month of life can all contribute to negative EOL experiences. These are more likely to occur for AYA patients than with older adults or young children. Moreover, most AYA patients die in the acute-care setting. Findings from a 2021 study published in 

 estimated that 69% of AYA patients pass away while admitted.

Investigators sought to better understand patient preferences—specifically, preferential EOL locations.1 Therefore, they conducted quantitative interview studies of AYA patients with advanced disease and compiled responses along with the responses of their family caregivers and clinicians. Interviews occurred between December 6, 2018, and January 5, 2021. Eligible participants were identified from clinical lists, administrative databases, and clinician referrals. The study included a total of 80 individuals: 23 patients, 28 family caregivers, and 29 clinicians.

The interviews revealed that multiple factors influence an AYAs choice of death location. The driving rationale comes from a want to be around family and friends but other reasons for include a desire for comfort, a sense of normalcy, and wanting to be protected from the isolation of being in the hospital.

One participant stated: “Rather than being in a situation where my last days are spent on a hospital bed and my parents and my loved ones have to come to the hospital, I would rather kind of share those experiences in the last days in a home – I would rather pass at home.”

External factors, however, may influence an AYA patient’s decision, and persuade them to elect an in-hospital death. One reason for this may be that there are more logistical considerations necessary for an at-home death. Caregivers were more likely to recognize these logistical considerations, which include need for pain and symptom management.

One caregiver described circumstances surrounding a patient that would influence admission to a hospital being preferential. “Had she experienced a tremendous amount of pain, we would have sought another way of you know either getting continuous IV [intravenous] morphine…or we would have brought her back to the hospital,” the caregiver responded. “And although she wouldn’t have wanted that decision, the pain decision would have superseded the decision to keep her home.”

A clinician backed that sentiment, noting, “Most [individuals] feel it would be nice to be at home, but then the question is: at what cost?… The symptom burden is high here—few [individuals] that I’ve met are willing to be at home at the cost of risk of symptom control.”

Moreover, there is the desire of the caregiver to preserve the home as a place “untouched” by death, particularly for the benefit of a sibling, which may persuade AYA patients to choose a hospital death. One caregiver acknowledged that her family did not want to “mar” their home space and did not want the patient’s younger sibling to witness her brother’s death.

Although most AYAs expressed that they would prefer to pass away at home, they also acknowledged a family member preference and, consequently, they expressed concern about imposing additional trauma on their family members if they choose to stay at home. The desire to experience EOL comfort for themselves, and the need to not to be a burden to their family, created a tension that was identified in the study. Results noted that many AYAs chose a hospital-death specifically to limit the potential burden on their family members.

Lastly, the need for hospice care is at odds with the desire to pass away at home. Although hospice care can be useful in facilitating an at-home death, there are limitations, and some families may opt to bring their loved one in for inpatient hospice care despite patient preferences. For example, a bereaved caregiver reported that their loved one died in a hospice house rather than at home because of inability to access the high level of care needed to facilitate a home death.

Another stated, “One thing I wish is that in-home hospice services would be able to do 24-hour care, not nursing care, but [provide an] aide to stay with the patient. Because I had to put him in a hospice house because he couldn’t die at home because I couldn’t care for him anymore. That was hard for me.”

Although at-home hospice services represent an interesting tactic to try and make at-home deaths feasible, gaps still remain in this type of care and will need to be expanded if families are truly able to take advantage of these services rather than inpatient hospice. Similarly, robust home-based services for symptom control and logistical/psychosocial support for family caregivers and siblings are imperative and warrant further investigation.

Given the stress that surrounds EOL experiences, seeking invocative solutions to improve the level of comfort for these patients is necessary, the authors concluded.

Odejide OO, Fisher L, Kushi LH, et al. Patient, family, and clinician perspectives on location of death for adolescents and young adults with cancer. 

Published online August 18, 2022. doi:10.1200/OP.22.00143

Coltin H, Rapoport A, Baxter NN, etc. Locus-of-care disparities in end-of-life care intensity among adolescents and young adults with cancer: a population-based study using the IMPACT cohort. 

 2022;128(2):326-334. doi:10.1002/cncr.33926.

Innovative strategies are needed to ensure that adolescents and young adults with cancer who prefer to die at home are able to make that choice.

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

Results from the Sexual Health Assessment in Women with Lung Cancer (SHAWL) study highlight the need for health interventions in thoracic oncology care, according to Narjust Florez, MD.

Among 127 participants who had attempted sexual activity within 30 days of completing a survey, 77% reported moderate to severe sexual dysfunction. Of these, 59% (n = 75) had experienced significant issues with vaginal dryness and 26% (n = 63) had experienced vaginal discomfort during sexual activity.

In a direct comparison before and after a diagnosis of lung cancer, there were stark changes in sexual desire and interest (15% vs 31%; 

 < .001) and vaginal pain and discomfort (13% vs 43%; 

“The results were sobering,” Florez said in a presentation during the IASLC 2022 World Conference on Lung Cancer. Florez is associate director of the Cancer Care Equity Program and a thoracic medical oncologist at the Lowe Center for Thoracic-Oncology and the Dana-Farber Institute. “This means [that] this is affecting the patient’s quality of life. This is a daily matter for many of these patients.”

Florez said that the study did not limit sexual health to penetrative/vaginal sex, but encompassed all forms of intimacy, such as cuddling, kissing, oral sex, and masturbation. The study results showed that female patients with lung cancer were experiencing moderate to severe changes in various intimate settings.

According to Florez, most patients with lung cancer (up to 95%) receive a sexual dysfunction score below the 50th percentile and, unfortunately, most sexual dysfunction–related issues do not improve over time. Sexual dysfunction has been linked to higher symptom distress and worse functional status.

Despite previous efforts have been undertaken to catalogue the experiences of this patient population, few data exist regarding how patients receiving checkpoint inhibitors and targeted therapies have been affected by changes in sexual health. The effect of newer treatment strategies on patients’ sexual health is largely under-reported, and consequently understudied, Florez said.

The SHAWL study was an observational, cross-sectional, international effort to query patients about their experiences. The study used PROMIS questions in a self-reported online questionnaire and was administered to patients with lung cancer in collaboration with the GO2 Foundation for Lung Cancer and the lung cancer registry.

The survey queried 249 participants. The age range was 29 to 84 years, and the average age of respondents was 59.9 years. Most patients were non-Hispanic Whites (88%) and 81% had a diagnosis of non–small cell lung cancer. Nearly half (45%) were receiving a targeted therapy treatment.

The findings showed that the factors most likely to affect sex life satisfaction included fatigue (40%), feelings of unhappiness (28%), issues with partners (22%), and shortness of breath (15%). Florez noted that shortness of breath is a factor unique to this patient population.

Study authors acknowledged that this study was limited to the US and primarily consisted of non-Hispanic White participants, and that, because sexual health is influenced by cultural beliefs, this represents a limitation. Moving forward, the Florez and other coinvestigators plan to launch the intervention phase of research and seek ways to improve the quality of life for patients who are facing sexual health changes.

Florez N, Acharya R, Wei1 Z, et al.Sexual health assessment in women with lung cancer (SHAWL) study. Presented at: IASLC 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. Abstract MA14.04

Sarna L. Correlates of symptom distress in women with lung cancer. Cancer Pract. 1993;1(1):21-28.

Bober SL, Sanchez Varela V. Sexuality in adult cancer survivors: challenges and intervention. J Clin Oncol. 2012;30(30):3712-3719. doi:10.1200/JCO.2012.41.7915

Findings from the SHAWL study found that sexual dysfunction rates are high among women with lung cancer. 

Integration of Sexual Health Considerations Into Thoracic Oncology Care Is Critical 

-positive non–small cell lung cancer, adding chemotherapy to treatment with gefitinib (Iressa) may be more effective in prolonging time to second progression (PFS2) vs treatment with gefitinib alone, according to an updated analysis of the phase 3 NEJ009 trial (UMIN000006340) published in the 

Notably, the preplanned PFS2 analysis was inappropriate because of the influence of post–progressive disease treatment period that was included only for the gefitinib group. The corrected definition of PFS2 in the gefitinib group omitted this period.

Findings showed that patients treated with gefitinib plus chemotherapy (n = 169) achieved a corrected median PFS2 of 20.9 months (95% CI, 18.0-24.0) compared with 18.0 months (95% CI, 16.3-20.7) for patients treated with gefitinib alone (n = 172; HR, 0.77; 95% CI, 0.62-0.97; 

An additional analysis of PFS2 with the same definition showed that the updated median PFS2 was 32.5 months (95% CI, 29.0-36.6) for the gefitinib plus chemotherapy group vs 20.7 months (95% CI, 17.9-24.6) for the gefitinib alone group (HR, 0.58; 95% CI, 0.46-0.73; 

“These persistent survival benefits confirmed that combination therapy with EGFR-TKI and chemotherapy boosted the tumor response and duration of response than EGFR-TKI monotherapy in patients with 

-mutated NSCLC,” wrote lead study author Eisaku Miyauchi, MD, PhD, a physician in the Department of Respiratory Medicine at Tohoku University Hospital in Sendai, Japan, and colleagues.

the FDA approved single-agent gefitinib for the frontline treatment of patients with metastatic

 with an exon 19 deletion or exon 21 (L858R) substitution.

 The multicenter, open-label NEJ009 trial evaluated single-agent gefitinib with or without chemotherapy to investigate the efficacy and safety of the 2 regimens.

Previous findings from the trial showed that the combination elicited an overall response rate (ORR) of 84% compared with 67% for gefitinib alone, and the median progression-free survival (PFS) for the combination and single-agent was 20.9 months and 11.9 months, respectively.

The trial enrolled patients aged 20 to 75 years with chemotherapy-naïve stage IIIB or IV or relapsed nonsquamous NSCLC harboring 

 mutations. Patients were also required to have an ECOG performance status of 0 or 1, plus adequate organ function.

Patients were excluded from the trial if they had serious concomitant systemic disorders, interstitial pneumonia, another primary malignancy, preexistence of an 

 T790M mutation, symptomatic brain metastases, or pregnancy.

Once enrolled, patients were randomly assigned 1:1 to gefitinib alone or gefitinib plus chemotherapy. All patients received 250 mg of oral gefitinib once per day, and patients in the combination arm also received carboplatin area under the curve 5 and 500 mg/m

of pemetrexed in a 3-week cycle for up to 6 cycles, followed by concurrent gefitinib and pemetrexed maintenance. If patients in the combination arm were intolerant of gefitinib or chemotherapy, they were permitted to continue treatment on the remaining agents. Protocol called for treatment to end at disease progression, though patients were allowed to continue treatment at investigator discretion.

Notably, since osimertinib (Tagrisso) was approved for the treatment of 

 T790M–mutated NSCLC, 21.8% and 23.3% of patients in the combination arm and gefitinib arm, respectively, received osimertinib in any treatment line. In the gefitinib group, 26.7% of patients did not receive platinum-based chemotherapy in any setting.

The coprimary end points of the trial included PFS, PFS2, and overall survival (OS). Secondary end points consisted of ORR, safety, and quality of life.

Baseline characteristics of age and sex were consistent across the 2 arms. The majority of patients never smoked (56.5% and 56.4% in the combination and gefitinib arms, respectively), had an ECOG performance status of 0 (57.6% and 62.2%), had adenocarcinoma (98.8% and 98.8%), had stage IV disease (81.8% and 79.7%), did not have brain metastases (70.6% and 77.9%), did not have liver metastases (90% and 93%), and had an 

Updated OS data showed that there was no significant difference between the 2 groups. In the combination arm, the mean OS, 2-year OS rate, and 5-year OS rate were 49.0 months, 77.1%, and 39%, respectively. Those data were 38.5 months, 69%, and 34%, respectively, in the gefitinib arm (HR, 0.822; 95% CI, 0.639-1.058; 

“In the subgroup analysis, the OS benefit for [gefitinib plus chemotherapy] and gefitinib [alone] was comparable in the overall patient population, including the type of 

 activation mutation and metastatic sites. However, larger numerical between-group differences in the HRs for OS were observed between male and female patients,” study authors noted.

Additionally, the 5-year restricted mean survival time (RMST) was 43.6 months in the combination group compared with 38.6 months for the gefitinib group (

 = .017). The 7-year RMST was 51.6 months and 45.3 months in the combination arm and gefitinib arm, respectively (

 = .037). The RMST analysis revealed a statistically significant 6.3-month survival advantage for the combination regimen over a 7-year follow-up period.

Regarding safety, 66.5% of patients in the combination arm experience at least 1 grade 3 or higher treatment-related adverse effect (TRAE) compared with 31% in the gefitinib arm (odds ratio, 0.23; 95% CI, 0.15-0.36; 

 < .001). One grade 1 TRAE (infection) occurred in the combination group, and no new instances of interstitial lung disease were reported.

“The [gefitinib plus chemotherapy] regimen improved PFS and PFS2 with an acceptable safety profile than [compared] with gefitinib alone. Clinical trials are ongoing to compare efficacy of osimertinib monotherapy with osimertinib combined with platinum plus pemetrexed as first-line treatment for patients with untreated NSCLC with 

Miyauchi E, Morita S, Nakamura A, et al. Updated analysis of NEJ009: gefitinib-alone versus gefitinib plus chemotherapy for non–small-cell lung cancer with mutated EGFR. 

. Published online August 12, 2022. doi: 10.1200/JCO.21.02911

Iressa approved by US FDA for first-line treatment of patients with advanced 

 mutation-positive non-small cell lung cancer. News release. AstraZeneca. July 13, 2015. Accessed August 24, 2022. 

Hosomi Y, Morita S, Sugawara S, et al. Gefitinib alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 study. 

. 2020;38(2):115-123. doi:10.1200/JCO.19.01488

Compared with gefitinib monotherapy, a combo regimen of gefitinib plus chemotherapy generated superior time to second progression in untreated non–small cell lung cancer. 

Gefitinib Plus Chemotherapy Proves Effective in EGFR-Mutated Non–Small Cell Lung Cancer

Before deciding on a single treatment strategy to manage vancomycin-infusion reactions (VIR), oncology providers should consider therapeutic implications, according to a report published in the 

Journal of Hematology and Oncology Pharmacy

Gram-positive bacterial infections represent a major mortality risk for patients with cancer. Vancomycin is an antibiotic that is administered intravenously (IV) to treat bacterial infections, making appropriate use a key factor in supporting this patient population.

VIR is a well-documented hypersensitivity reaction that is common across diverse patient populations. Key signs that a patient is experiencing VIR include flushing, pruritus, chest pain, muscle spasm, and hypotension. The typical onset time of reactions is 15 to 40 minutes into the infusion; they may continue for the duration of the infusion. The typical resolution time is 30 minutes after treatment.

Severity of VIR is typically classified into 3 different thresholds. A mild reaction is when a patient can tolerate flushing and other symptoms. A moderate reaction means a patient may be uncomfortable because of flushing or pruritis but is hemodynamically stable and is not experiencing muscle spasms and chest pain. A severe reaction, on the other hand, means a patient is experiencing muscle spasms, chest pains, and hypotension.

VIR, though common, is usually mild and easily treatable. However, it has the potential to cause severe reactions in some individuals. Severe VIR is more common in patients older than 40 years.

According to study authors, best management strategies may include premedication, infusion-rate adjustment, and, in some cases, alternative antibiotic therapy.

Multiple studies have assessed the efficacy of antihistamine pretreatment to prophylaxis against VIR severity. Rapid vancomycin administration, when the infusion rate is less than or equal to 10 mg/minute, is often required in an emergency or presurgical setting, but comes with inherent risk of VIR. Both oral and IV histamine type 1 antagonists, such as hydroxyzine or diphenhydramine below 1 mg/kg, and type 2 antagonists, such as cimetidine below 4 mg/kg have demonstrated promising efficacy in reducing the effects of rapid vancomycin administration, yet patients will still require careful monitoring for subsequent doses.3-6 These H1 and H2 antagonists have also showed promising efficacy in reducing the severity of VIR symptoms in patients who have already developed moderate or severe reactions. 

Concurrent Medication and Infusion-Rate Adjustments

For patients who develop moderate or severe VIR and need to hold medication, the introduction of 50-mg diphenhydramine (oral or IV) and 20-mg IV famotidine may be appropriate, according to clinical guidelines.5 Alternatively, the use of IV fluids may be successful in achieving hemodynamic stabilization in a hypotensive patient. Once a patient has returned to their precreation clinical status, vancomycin may be reintroduced. However, a reduced infusion rate is advised.

When restarting vancomycin infusion, either a 50% reduction in rate speed or a decrease to below 1000 mg/hour, with a target of 10 mg/minute, is advised. The slower the better. One possible strategy proposed by Healy et al extends the duration time from 1 hour to 2 hours, as trough concentrations and areas under the curve are similar for both these infusion times.

 Moreover, more frequent, lower doses of vancomycin may also be an effective strategy. For example, 500 mg every 6 hours instead of 1 g every 12 hours may be preferable. However, this method may pose some relevant pharmacokinetic, workflow, and financial implications.

If vancomycin is the only effective antibiotic available for a patient who experienced VIR with the first dose, they should be pretreated with a histamine type 1 antagonist and the infusion rate should be extended so that it lasts over 2 hours.

However, for patients with a history of VIR, antibiotics with similar activity and efficacy to vancomycin may be considered. It is important to note that patients receiving these treatments will still require routine monitoring and nuanced dosing and infusion rates.

Daptomycin, a cyclic lipopeptide antibiotic, or telavancin, dalbavancin, and oritavancin, all semisynthetic lipoglycopeptide antibiotics (and vancomycin analogs), are recommended alternative treatments for patients requiring antibiotic infusion.

For skin and skin-structure infections, the recommended daptomycin dose is 4 to 6 mg/kg once daily. For bloodstream infections, the standard dose increased to 8 to 10 mg/kg once daily. The standard duration with daptomycin is 5 to 14 days.

Alternatively, telavancin is typically prescribed at 10 mg/kg once daily for at least 14 days for blood stream infections. Oritavancin and dalbavancin represent long-acting antibiotic; for skin and soft-tissue infections, their recommended doses are 1.2 g and 1.5 g, respectively.

The adverse events associated with these alternative treatments are limited and less frequent than with vancomycin. Pseudoallergic VIR symptoms may occur and are best managed with slower infusion rates.

Teicoplanin is a drug with an antibacterial spectrum like vancomycin; however, this agent is currently only used outside the United States. Its profile suggests it may be a safer alternative for patients who cannot tolerate a vancomycin-induced release of histamine. The recommended loading dose for teicoplanin is 6 mg/kg twice daily for 48 hours for complicated infection, followed by a maintenance dose of 6 mg/kg once daily. Because this treatment is not widely available, it is recommended to consider the alternatives first.

“The percentage of patients who require an alternative therapy for VIR is generally low, but considerable variability exists in this area, because rarer forms of vancomycin hypersensitivity, which can manifest as IgE-mediated [immunologic] anaphylaxis, drug-induced hypersensitivity syndrome, or linear IgA bullous dermatosis, may still necessitate such treatment,” study authors noted.

“Appropriate precautions may also be taken before the use of an alternative antibiotic therapy is considered, including slowing the infusion rate and completing relevant premedication or coadministration of H1 and H2 antagonists. For patients with a history of anaphylaxis to vancomycin, alternative therapy with nonglycopeptide antibiotic is recommended whenever possible,” they concluded.

Haque S, Cubbison C, Pucik K, Bubalo J. Vancomycin infusion reaction: a clinical and therapeutic overview

Alqahtani S, Almatrafi A, Bin Aydan N, et al. Optimization of vancomycin dosing regimen in cancer patients using pharmacokinetic/pharmacodynamic modeling

 2020;40(12):1192-1200. doi:10.1002/phar.2475

Wallace MR, Mascola JR, Oldfield EC III. Red man syndrome: incidence, etiology, and prophylaxis

Weller PF. Vancomycin hypersensitivity. UpToDate. Wolters Kluwer; 2021. AccessedAugust 25, 2022

Renz CL, Thurn JD, Finn HA, et al. Oral antihistamines reduce the side effects from rapid vancomycin infusion. 

Sahai J, Healy DP, Shelton MJ, et al. Comparison of vancomycin- and teicoplanin-induced histamine release and “red man syndrome.” 

Best management strategies for vancomycin infusion reactions may include premedication, infusion-rate adjustment, and, in some cases, alternative antibiotic therapy. 

New Research Sheds Light on Optimal Management of Vancomycin Infusion Reactions

Providers concerned about improving tolerability with sotorasib (Lumakras) plus pembrolizumab (Keytruda) or atezolizumab (Tecentriq) may consider a lead-in dosing strategy, according to data presented at the 

. The findings showed that this strategy demonstrated promising efficacy and relatively low rates of hepatoxicity in patients with 

 G12C–positive non–small cell lung cancer (NSCLC).

Across all treated patients (n = 58), the objective response rate (ORR) was 29% (95% CI, 18%-43%), comprised of 2 complete responses and 15 partial responses, and the disease control rate was 83% (95% CI, 71%-91%). The median duration of response was 17.9 months (95% CI, 5.6-not evaluable). Of note, responses were similar in immunotherapy-pretreated and -naïve patients. Overall survival with any sotorasib/PD-1 inhibitor combination was 15.7 months (95% CI, 9.8-17.8).

Due to the durable efficacy and safety of low-dose sotorasib as lead-in therapy followed by concurrent use with pembrolizumab, this regimen will be studied further as frontline treatment in patients with 

 by the FDA as monotherapy for patients with previously treated 

 G12C–mutant NSCLC as determined by an FDA-approved test based on results from the 

 Preclinical evidence has suggested that PD-1 inhibition may synergize with sotorasib to enhance CD8-positive T-cell infiltration and inhibit tumor growth.

In the current analysis, patients from the phase 1/2 CodeBreak 100 and CodeBreak 101 (NCT04185883) trials who were administered sotorasib plus either atezolizumab or pembrolizumab were examined for efficacy and safety. The primary end point was 

 with secondary outcomes of ORR, duration of response (DOR), disease control rate (DCR), and pharmacokinetics.

Patients (N = 58) were included if they had advanced 

 G12C–mutated NSCLC, received or refused prior standard therapy, no prior experience with a KRAS G12C inhibitor, and no active brain metastases. All participants were randomized to an oral daily dose of sotorasib ranging from 120 mg to 960 mg. Half of the patients were first treated with a 21- or 42-day lead-in of sotorasib followed by treatment in combination with atezolizumab at 1200 mg (n = 10) or pembrolizumab at 200 mg (n = 19) every 3 weeks; the other half were treated with combination therapy of atezolizumab/sotorasib (n = 10) or pembrolizumab/sotorasib (n = 19) from the outset.

The median patient age was 66 years (range, 29-86), most had a history of smoking (93%), and the median number of prior therapies was 1 (range, 0-7). There were 12 patients (21%) who were receiving the combination as frontline therapy and 39 (67%) had been previously treated with an anti–PD-1/L1 agent. Most patients had an ECOG performance score of 1 (81%), 31% had brain metastases, and 26% had liver metastases. PD-L1 expression was under 1% in 10 patients (17%), between 1% and 49% in 16 (28%), and 50% or above in 21 (36%); the PD-L1 expression status was unknown for 11 patients.

For the patients who received concurrent pembrolizumab, sotorasib resulted in a high rate of hepatotoxic events, most of which were from liver enzyme elevation. Grade 3 hepatotoxicity across dose levels occurred at a rate of 80% in the 120 mg group (n = 5), 75% in the 360 mg group (n = 8), 100% in the 720 mg group (n = 2), and 75% in the 960 mg group (n = 4). Although sample sizes were small, lower starting doses of sotorasib trended toward fewer events of enzyme elevation leading to experimentation with the sotorasib lead-in dosing strategies.

For patients receiving pembrolizumab and a safety lead-in of sotorasib, grade 3 or greater treatment-related AEs (TRAEs) occurred in 100% of those in the 120 mg group (n = 3), 20% in the 240 mg group (n = 5), and 55% on the 360 mg group (n = 11). The rate of grade 3 hepatotoxicity in each respective group was 67%, 20%, and 45%. Overall safety data from both the lead-in and concurrent administration groups suggested a lower starting dose of sotorasib and lead-in administration is preferable for better tolerability.

Looking at all treatment arms, lead-in treatment strategies resulted in fewer overall and grade 3/4 TRAEs, discontinuations, and hepatotoxicity vs concurrent therapy. The first occurrence of grade 3/4 hepatotoxicity was outside the dose-limiting toxicity window in 88% of patients with 97% of cases resolving with corticosteroids or treatment modification and/or discontinuation. Notably, pretreatment with immunotherapy did not appear to influence the rate of treatment-related hepatotoxicity.

For the patients treated with atezolizumab/sotorasib, grade 3/4 TRAEs occurred at rates of 30% and 0% in those treated with lead-in therapy vs 50% and 10%, respectively, with the combination. Treatment discontinuation of either atezolizumab or sotorasib due to TRAEs occurred in 10% of those treated with lead-in therapy vs 50% on a concurrent regimen. Median treated duration was longer in the lead-in group at 6.5 months (range, 1-18) vs 4.4 months (range, 1-14) with concurrent therapy, whereas the median duration of combination therapy specifically was shorter at 1.5 months (range, 0-18) vs 2.5 months (range, 1-14), respectively. Median onset of hepatoxicity was shorter with the lead-in regimen at 50 days (range, 28-93) vs 67 days (range, 36-147) with concurrent treatment.

For the patients treated with pembrolizumab/sotorasib, grade 3/4 AEs occurred at rates of 53% and 0% in those treated with lead-in therapy vs 74% and 5%, respectively, with the combination. Treatment discontinuation of either atezolizumab or sotorasib due to TRAEs occurred in 32% of those treated with lead-in therapy vs 53% on a concurrent regimen. Median treatment duration was longer in the lead-in group at 2.8 months (range, 1-15) vs 4.9 months (range, 2-30) with concurrent therapy, whereas the median duration of combination therapy specifically was shorter at 0.7 months (range, 1-15) vs 2.3 months (range, 1-9), respectively. Median onset of hepatoxicity was shorter with the lead-in regimen at 73 days (range, 45-127) vs 51 days (range, 29-190) with concurrent treatment.

Li BT, Falchook GS, Durm GA, et al. CodeBreaK 100/101: first report of safety/efficacy of sotorasib in combination with pembrolizumab or atezolizumab in advanced 

 p.G12C NSCLC. Presented at: 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. Abstract OA03.06.

FDA grants accelerated approval to sotorasib for KRAS G12C mutated NSCLC. News Release. FDA. May 28, 2022. Accessed August 7, 2022. https://bit.ly/3Q7hDff

Canon J, Rex K, Saiki AY, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. 

. 2019;575(7781):217-223. doi:10.1038/s41586-019-1694-1

Sotorasib is often associated with a high rate of hepatotoxic events, most of which are from elevated liver enzymes. However, a lead-in dosing strategy may help address this adverse event and improve patient tolerability. 

Experimental Dosing Strategy With Sotorasib Plus Immunotherapy Helps Combat Hepatotoxicity in KRAS G12C+ NSCLC

In August 2022, the relationship between nutrition and cancer was put to the test: myths surrounding sugar, soy, and vegan diets, and their ability to improve or injure patient outcomes were debunked. Similarly, the American Society of Clinical Oncology (ASCO) released updated guidelines with recommendations for diet and exercise for patients undergoing active treatment.

Oncology nurse research took center stage as new findings showed that taxane-based chemotherapy caused hearing loss in the majority of patients with breast, gastrointestinal, gynecological, or lung cancer. 

® discussed the findings and implications in clinical practice in an exclusive interview with principal investigator Christine Miaskowski, PhD, RN.

Finally, nurses play a powerful role in improving the quality of care for patients. Hear from experts how nurses can help ensure that patients with ovarian cancer receive optimized treatment plans, as well as help create an inclusive environment for all they attend to in their practice.

Dispelling Nutrition Myths for Patients With Cancer

Entering the words nutrition and cancer into Google returns as many as 718 million hits. With an overabundance of opinions, it can be challenging to separate fact from fiction. Therefore, in this feature, Nicole Franklin, MS, RDN, CSO, LDN, a registered dietician with the American Oncology Network, calls out 3 commonly held myths about nutrition and cancer and uncovers the bottom line.

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

New research efforts led Christine Miaskowski, PhD, RN, show that most adult cancer survivors who undergo treatment with either a platinum-based chemotherapy, taxane alone, or a combined regimen of platinum- and taxane-based treatment, experience some degree of hearing loss. In an interview with 

 Miaskowski, a professor in the Department of Physiological Nursing and Anesthesia at UCSF School of Nursing, highlights what these findings mean for clinical practice.

Nurses Play Key Role in Facilitating Maintenance Therapy With PARP Inhibitors in Ovarian Cancer

®, Paula Anastasia, RN, MN, AOCN, a gynecologic Oncology Clinical Nurse Specialist for UCLA Health, offers a recap of her presentation at 

. She discusses ways in which nurses can help facilitate maintenance therapy with PARP inhibitors such as olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula), and emphasizes the value of germline testing for this patient population.

ASCO Outlines Recommend Aerobic and Resistance Exercises for Patients Undergoing Active Cancer Treatment

ASCO recently convened a panel of experts to conduct a comprehensive literature review of existing data regarding the role of diet, weight, and exercise in defining patient outcomes. The updated guidelines formally recommend aerobic and resistance exercises for patient with cancer, although they note that this is an area of research that continues to be overlooked in clinical trial designs.

1. Addressing Disparities: Practicing Inclusion for LGBTQ+ Patients With Cancer

Identifying and acknowledging disparities helps providers work together to improve access to care and treatment and reduce the cancer risks. Among individuals in the LGBTQ+ community there is less access to care because of a lack of inclusive health care, underrepresentation and exclusions in clinical trials, and lack of coverage for appropriate screenings.

In this feature, our partners at Cancer Care outline key ways that nurses can improve their care delivery and create a practice that is inclusive for marginalized communities.

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

Lung Cancer