The FDA has given the go-ahead to a combination of tremelimumab-actl (Imjudo) plus durvalumab (Imfinzi) and platinum-based chemotherapy for patients with non-small cell lung cancer and no 

The regulatory decision was supported by findings from the pivotal phase 3 POSEIDON trial (NCT03164616). To be eligible for enrollment, patients were required to have an ECOG performance status of 1 or less. They also can not have previously received chemotherapy or another systemic treatment for metastatic disease.

Exclusion criteria included active and/or untreated brain metastases, a history of active primary immunodeficiency, autoimmune disorders, or the use of systemic immunosuppressants within 2 weeks before the first dose of study treatment.

Study participants were randomly assigned to 1 of the following 3 treatment arms: tremelimumab plus durvalumab and platinum-based chemotherapy (arm 1), durvalumab plus platinum-based chemotherapy (arm 2), or platinum-based chemotherapy (arm 3). The evaluation of efficacy relied on a comparison between the 675 patients enrolled to arms 1 (n = 338) and 3 (n = 337):

Tremelimumab at 75 mg or 1 mg/kg in those < 30 kg plus durvalumab at 1500 mg and platinum-based chemotherapy every 3 weeks for 4 cycles, followed by durvalumab monotherapy at 1500 mg every 4 weeks. A fifth dose of tremelimumab at 75 mg was given at week 16 in combination with the six dose of durvalumab.

Platinum-based chemotherapy given every 3 weeks as monotherapy for 4 cycles. Patients were allowed to receive an additional 2 cycles for a total of 6 cycles following randomization per investigator discretion.

Treatment continued until patients experienced progressive disease or intolerable toxicity. Patients were stratified based on PD-L1 expression on tumor cells (≥ 50% vs < 50%), disease stage (stage IVA vs stage IVB), and histology (nonsquamous vs squamous).

The primary outcome measures for the trial included overall survival (OS) and progression-free survival (PFS) by blinded independent central review and in accordance with RECIST v1.1 criteria. Additional outcome measures comprised overall response rate (ORR) and duration of response (DOR).

The median age of patients in arms 1 and 3 was 63 years (range, 27-87), and 46% of patients were aged 65 years or older. Seventy-seven percent of patients were male, 57% were White, and 79% were former or current smokers. Regarding performance status, 34% had a status of 0, and the remaining 66% had a status of 66%. In terms of histology, 36% of patients had squamous disease and 63% had nonsquamous disease. In terms of PD-L1 expression, 29% had tumor cell expression of at least 50% and 50% had expression of less than 50%.

The combination of tremelimumab, durvalumab, and chemotherapy significantly improved OS over chemotherapy alone, at 14 months (95% CI, 11.7-16.1) vs 11.7 months (95% CI, 10.5-13.1), respectively; this translated to a 23% reduction in the risk of death (HR, 0.77; 95% CI, 0.65-0.92; 2-sided 

Moreover, those in arm 1 also experienced improved PFS over those in arm 3, at 6.2 months (95% CI, 5.0-6.5) and 4.8 months (95% CI, 4.6-5.8), respectively; this correlated to a 28% reduction in the risk of disease progression or death (HR, 0.72; 95% CI, 0.60-0.86; 2-sided 

Tremelimumab plus durvalumab and platinum-based chemotherapy elicited an ORR of 39% (95% CI, 34%-44%) vs 24% (95% CI, 20%-29%) with platinum-based chemotherapy alone. The median DOR in arm 1 was 9.5 months (95% CI, 7.2–not reached) vs 5.1 months (95% CI, 4.4-6.0) in arm 3.

A total of 330 patients in arm 1 were evaluable for safety. The most common toxicities reported with the regimen, that were reported in at least 20% of patients, were nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea. Grade 3 or 4 laboratory abnormalities experienced by at least 10% of patients comprised neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia and thrombocytopenia.

Serious toxicities were reported in 44% of patients who received the combination. The most common serious adverse effects included pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%).

Moreover, 4.2% of patients experienced fatal adverse reactions, which included hepatitis, nephritis, myocarditis, pancreatitis (all in the same patient); death (n = 2); sepsis (n = 2); pneumonitis (n = 2); acute kidney injury (n = 2); febrile neutropenia (n = 1); chronic obstructive pulmonary disease (n = 1); dyspnea (n = 1); sudden death (n = 1); and ischemic stroke (n = 1).

Forty-one percent of patients required dose interruptions or delays of tremelimumab or durvalumab due to toxicity; these effects included anemia, leukopenia/white blood cell count decreased, pneumonia, pneumonitis, colitis, diarrhea, hepatitis, rash, asthenia, amylase increased, alanine aminotransferase increased, aspartate aminotransferase increased, lipase increased, neutropenia/neutrophil count decreased, and thrombocytopenia/platelet count decreased.

Seventeen percent of patients discontinued tremelimumab or durvalumab because of an adverse effect. The toxicity that resulted in permanent treatment discontinuation of either agent in more than 2% of patients was pneumonia.

FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non-small cell lung cancer. News release. FDA. November 10, 2022. Accessed November 10, 2022. http://bit.ly/3Ej7yIx

Imjudo (tremelimumab-actl). Prescribing information; AstraZeneca Pharmaceuticals; 2022. Accessed November 10, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761270s000lbl.pdf

Imfinzi (durvalumab). Prescribing information; AstraZeneca Pharmaceuticals; 2022. Accessed November 10, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761069s033lbl.pdf

Articles

The FDA has given the go-ahead to a combination of tremelimumab-actl (Imjudo) plus durvalumab (Imfinzi) and platinum-based chemotherapy for patients with non-small cell lung cancer and no EGFR mutations or ALK aberrations.

Durvalumab/Tremelimumab/Chemotherapy Combination Approved for NSCLC Indication

Brain metastases have historically been associated with dismal outcomes. However, while former treatment approaches were centered around surgery or radiation, in the past decade and a half, investigators have made transformative advances in unlocking the scientific understanding of the genomic drivers behind cancer, according to Manmeet Ahulwalia, MD, MBA. Consequently, the oncology community has made great strides in precision medicine and immunotherapy: 2 approaches which are significantly improving outcomes for patients with brain metastases.

Ahulwalia, the Fernandez Family Foundation Endowed Chair in Cancer Research, Chief of Medical Oncology, and Chief Scientific Officer & Deputy Director, Miami Cancer Institute, Baptist Health South Florida, recently presented on the management of brain and leptomeningeal metastases across tumor types during the 

, he underscored how the evolution of treatment directions across tumor types have unlocked promising opportunities to penetrate the blood brain barrier.

Some of the cancers which have a greater tendency to metastasize to the brain include lung cancer, breast cancer, and melanoma. According to Ahulwalia, all of these subtypes have seen tremendous progress in the past 2 decades in terms of treatment options and outcomes According to Ahulwalia, patients with lung cancer and brain metastases in 2010 had, on average, an estimated overall survival of 9 to 12 months . However, today, patients with 

-mutant lung cancer which has metastasized to the brain are generally expected to survive an average of 2 to 3 years, and for patients with translocation lung cancer with brain metastases, the average survival has been prolonged to approximately 5 years. Small molecular inhibitors with promising blood brain barrier penetration have played a larger part in boosting survival in this arena.

Moreover, drugs like tucatinib (Tukysa) and, more recently, trastuzumab deruxtecan-nxki (Enhertu), have yielded encouraging results for patients with breast cancer and brain metastases. In the melanoma realm, a mere decade or 2 ago, the average survival was approximately 6 months—today immunotherapy advances are helping these patients achieve survival for nearly 4 or 5 years.

Unfortunately, patients with leptomeningeal disease still face dismal prognoses, Ahulwalia says. The good news is that certain patients with leptomeningeal disease now have promising treatments. For instance, osimertinib (Tagrisso) has shown promising benefit in patients with 

-mutant lung cancer, and patients with breast cancer have also experienced promising results with intrathecal based approaches. Ahulwalia expresses hope that the advances being made in this space will continue to ramp up in the coming decades and that new treatment approaches will open doors for patients with brain metastases and leptomeningeal disease.

“There have been transformative changes in the last decade or so, which make people like me extremely excited for our patients [and excited] about the progress that we're going to make in the next decade or two,” he concludes.

Videos

Manmeet Ahulwalia, MD, MBA, underscores how novel treatment approaches in oncology are proving effective in managing brain metastases. 

Ahulwalia on Targeting the Blood Brain Barrier With Novel Immunotherapies and Precision Oncology 

Several immunotherapy agents have received FDA approval across numerous malignancies since ipilimumab (Yervoy) a decade ago and, in many ways, the effect of immunotherapy in certain populations is equitable to magic, according to Melinda S. Weber, DNP, APN, AOCN-C. However, the unique mechanism of action associated with immunotherapy is also linked to adverse events (AEs) for patients receiving treatment.

In a presentation during the Nursing track at the 

 Weber who is the director of care transformation and a charge APN in the Skin and Sarcoma Division at John Theurer Cancer Center at Hackensack University Medical Center Weber, touched on the marked success of the treatment in the field in melanoma and outlined the tenets of early recognition, appropriate grading, and best management practices for these immune-related adverse events (irAEs).

Immunotherapeutic Agents Usher in a Wave of Hope

“Prior to the advent of ipilimumab [Yervoy] in 2011, [a diagnosis of] metastatic melanoma was a death sentence,” said Weber in an interview with 

 ahead of a presentation. “No radiation touched [the melanoma], no chemotherapy touched it, [and approximately] less than 1% of patients might survive [treatment with] high-dose IL-2 therapy, but that was very rare.”

In November 2022, approved immune-checkpoint inhibitors include atezolizumab (Tecentriq), avelumab (Bavencio), cemiplimab-rwlc (Libtayo), dostarlimab-gxly (Jermperli), durvalumab (Imfinzi), nivolumab (Opdivo), and pembrolizumab (Keytruda). Each of these regiments are approved across multiple indications.

Weber said that the efficacy that immunotherapy wielded in certain populations has been nothing short of astounding, and that it drastically changed her clinical practice.

“They’ve changed the face of oncology…I never thought in a million years that I would see PET scans, that were once lit up like a Christmas tree, become normal and stay normal over months, and then years. Now we have people that are survivors 10 years [or longer]….Our focus for those patients [with] late-stage disease was about palliative care, preserving their dignity, and optimizing their comfort. It was very sad.”

Weber said that the availability of these drugs is exciting because they are helping many patients achieve remission, and for those who do not, immunotherapeutic agents may help individuals reach partial remission, prolonged duration of responses, and superior overall survival rates.

“I never take for granted when we bring in our patients for follow-up visits, because I will never forget what it was like before these drugs,” Weber said. “To see people now go on to live their lives, enjoy their families, watch their children and grandchildren grow, is incredible.”

However, Weber noted the start of the immunotherapy integration was not a smooth journey and shared that when immunotherapy first hit the scene, she had patients who chose not to continue treatment because the irAEs were so severe. According to Weber, as clinicians, you must do everything in your power to avoid that possibility, because patients could be forfeiting a chance at a partial or full remission.

The most common irAEs associated with immune-checkpoint inhibitors include fatigue, asthenia, musculoskeletal pain, decreased appetite, diarrhea, nausea, vomiting, pyrexia, cough, dyspnea, constipation, abdominal pain, rash, peripheral neuropathy, mucosal inflammation, alopecia and stomatitis.

Additionally, immune-checkpoint inhibition is also associated with pneumonitis, colitis, hepatitis, encephalitis, endocrinopathies, dermatologic adverse events, nephritis, renal dysfunction, solid organ transplant rejection, infusions-related reactions, and embryo-fetal toxicity.

According to the National Comprehensive Cancer Network (NCCN), a comprehensive baseline assessment of a patient’s current emotional, physical, and spiritual status, with attention to a patient’s social determinants of health, financial toxicity burden, and health literacy are important for early recognition and prompt intervention for irAEs. These factors may influence how and when patients report irAEs, and can influence whether a patient needs to be admitted following the emergence of irAEs. 

According to Weber, the key with irAEs is to catch them early and intervene as soon as possible, because the sooner that the reactions dissolve and therapy can continue, the greater the outcome the patient can expect to achieve.

Weber noted that nurses today may be able to leverage novel technologies such as mobile applications or software programs to track irAEs. Prior to the advent of these applications, research nurses would carry around binders with the common terminology criteria for adverse events (CTCAE) information when assessing patients.

Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only, intervention not indicated.

Gradw 2: Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL).

Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL.

Grade 4: Life-threatening consequences; urgent intervention indicated.

Although CTCAE provides this broad overview of irAE grading, Weber also provided an example of what the clinical presentation looks like for a common irAE, diarrhea.

Grade 1: Increase of < 4 stools per day over baseline; mild increase in ostomy output compared with baseline.

Grade 2: Increase of 4 to 6 stools per day over baseline; moderate increase in ostomy output compared with baseline; limiting instrumental ADL.

Grade 3: Increase of > 7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared with baseline limiting self-care ADL.

According to Weber, CTCAE criteria offer clear guidance into appropriate handling of various irAEs, and with early intervention, management is possible. However, she repeatedly stressed that these irAEs are not to be taking lightly, as they can represent a serious barrier to treatment for many patients.

“If I can get anything across, it is that irAEs represent real suffering. [They are] different from chemotherapy adverse reactions,” Weber said. “For example, immunotherapy-induced colitis is horrific, and patients, depending on the grade, may be frightened to leave their homes. Besides the abdominal cramping, the discomfort, the risk of dehydration malnutrition, for many patients, there may be embarrassment or fear of living a normal life, and they may not want to leave their house.”

Moreover, irAEs are different from chemotherapy-related toxicities, because they can occur at unexpected time intervals. These toxicities have varying onset times—they can appear as early as within the first 2 weeks of treatment, or 12 weeks in, they can even occur over 22 months past the last cycle of immunotherapy. Thus, the gravity of these toxicities, the threat they pose to patients, and the need for patient education, cannot be overemphasized.

“irAEs are profoundly debilitating for many, many patients,” she added. “Our job as nursing professionals, besides [providing] great patient education, must be knowing the patient’s baseline to where they are right now, teaching patients to call us early when anything is out of ordinary that’s didn’t not occur before these drugs to call us, and intervening as swiftly as possible.”

Nurses Play a Vital Role in irAE Management

Therefore, when a patient is embarking on immunotherapy, the oncology nurse adopts a unique role as a patient cheerleader.

“We have to be the person who provides knowledge and comfort to that patient,” Weber said. She noted that patients are often afraid of the AEs of their treatments, but nurses can help reassure them and let them know that there is a plan to manage their irAEs.…We tell patients ‘We are going to get you through this,’” Weber said. She added that she likes to tell patients that immunotherapy makes their immune system similar to hungry sharks.

“It’s important for patients to understand what’s happening to them and how we are going to intervene,” she said. “We use a multidisciplinary group, we need our nutritionist, our psychotherapist, we need [individuals] that can provide globally comprehensively care for that patient.”

When it comes to symptom management, there is an arsenal of strategies that clinicians can utilize to help their patients; however, the most important thing, according to Weber, is recognizing the effect these symptoms can have on a patient’s quality of life and reassure them that it can be diminished.

“You can do old-fashioned things. For example, with diarrhea you can [advise patients] to use the BRAT diet, given its within your institutions policies. You can give Imodium [loperamide], Lemotil [atropine and diphenoxylate], Bentyl [dicycloverine], etc. Teach them appropriate dosing of prednisone as ordered, and to get the [irAE] behind them so they can move on.

Weber stressed that there must be awareness alongside action. Nurses have a responsibility to recognize the anguish, pain, and sometimes embarrassment, that patients experienced with these therapies. In managing the patients’ physical symptoms, it is important to recognize the turmoil they can induce on the whole person.

“They are not just clinical symptoms; they really change the face of the patient’s and the family member’s perception of their treatment,” Weber emphasized. “We have to really inspire hope that it's not going to be this way forever,” she said.

Weber MS. Monitoring and managing toxicities associated with immune checkpoint inhibitors. Presented at: 

 CFS®; November 9-11, 2022; New York, NY.

Clinical practice guidelines in oncology. National Comprehensive Cancer Network. Management of Immune-Related Toxicities. Version 1.2022 February 28, 2022. Accessed November 9, 2022. bit.ly/3UK0VnZ

Common terminology criteria for adverse events (CTCAE) v5.0. November 27, 2017. Accessed November 9, 2022. bit.ly/3TlJF7n 

Immunotherapy has changed the face of cancer treatment, but requires appropriate irAE management to reach full potential. 

Maximizing Potential of Immunotherapy Requires Appropriate irAE Management

On November 8th, the FDA approved cemiplimab-rwlc (Libtayo) in combination with platinum-based chemotherapy for patients with advanced non–small cell lung cancer (NSCLC).

 The recommended dose is 350 mg intravenously (IV) for a course of 30 minutes every 3 weeks, and the agent comes in a single-dose vial. 

Patients receiving cemiplimab should not have 

 aberrations. They must also be ineligible for surgery, or definitive chemoradiation, or they must have metastatic disease.

The approval was backed by data from the 16113 trial (NCT03409614), which randomly assigned 466 treatment naïve patients with advanced NSCLC 2:1 to receive either immunochemotherapy or chemotherapy plus placebo. Overall survival (OS), progression-free survival (PFS), and overall response rates (ORR) represented the key outcomes. The median OS was 21.9 months (95% CI, 15.5-not evaluable [NE]) with immunochemotherapy and 13.0 months (95% CI, 11.9-16.1) with chemotherapy plus placebo. The median PFS between the 2 cohorts was 8.2 months (95% CI, 6.4-9.3) and 5.0 months (95% CI, 4.3-6.2), respectively (HR, 0.56; 95% CI, 0.44-0.70;

 <.0001). The confirmed ORR was 43% (95% CI, 38%-49%) and 23% (95% CI, 16%-30%), respectively.

Study 16113 was a randomized, multicenter, multination, double-blind active controlled trial. PD-L1 status was not considered in eligibility criteria, however those with EGFR, ALK, or ROS1 harboring tumors, patients who required systemic immunosuppression, or patients with ongoing or recent autoimmune disease, were excluded from the research.

Patients randomized to the experimental arm received cemiplimab plus platinum-based chemotherapy every 3 weeks for 4 cycles followed by a combination of cemiplimab and maintenance chemotherapy. Patients in the control arm received platinum-based chemotherapy plus placebo every 3 weeks for cycles, followed by maintenance with chemotherapy and placebo.

Chemotherapy consisted of any of the following combinations:

Carboplatin area under the curve (AUC) of 5 or 6 plus paclitaxel at 200 mg/m

Carboplatin AUC of 5 or 6 plus pemetrexed at 500 mg/m

In the trial, the most common adverse events (AEs) included alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite.

Patients who receive cemiplimab may be at risk of immune-mediated AEs, including pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic AEs, nephritis and renal dysfunction, or solid organ transplant rejection. Liver enzymes creatinine, and thyroid function should be assessed at baseline and periodically throughout treatment.

 Infusion-related reactions may also occur with treatment. In this case, the rate of infusion should be slowed, interrupted, or permanently discontinued, depending on severity.

In addition, patients who undergo allogeneic hematopoietic stem cell transplantation and PD-1/PD-L1 blocking antibodies are at risk of serious complications.

The prescribing label does not offer a recommended dose reduction for cemiplimab. However, in general, grade 3 irAEs warrant holding treatment, and grade 4 irAEs warrant permanent discontinuation. Patients with recurring grade 3 irAEs, or those who are unable to reduce their corticosteroids dose to 10 mg or less within 12 weeks of initiating steroids, will generally need to discontinue treatment.

Cemiplimab injection is a clear to slightly opalescent, colorless to pale yellow solution that may contain trace amounts of translucent to white particles. It should be stored in a refrigerator in the original carton. Nurses should not freeze or shake the solution.

FDA approves cemiplimab-rwlc in combination with platinum-based chemotherapy for non-small cell lung cancer. News release. FDA. November 8, 2022. Accessed November 9, 2022. 

Libtayo. Prescribing information. Regeneron Pharmaceuticals, Inc.; 2022. Accessed November 9, 2022. 

Cemiplimab, in combination with platinum-based chemotherapy, has been approved for patients with advanced non–small cell lung cancer with no EGFR, ALK, or ROS1 aberrations.

Cemiplimab Gets Go Ahead In Combination With Chemotherapy For Advanced NSCLC

For a downloadable version that you can print at home, check out our 

Fam-trastuzumab deruxtecan-nxki (Enhertu) is approved for the following indications: 

: Patients with unresectable or metastatic HER2-postitive breast cancer who previously received 2 or more anti–HER2-based regimens 

: Patients with locally advanced or metastatic HER2-postitive gastric or gastroesophageal junction (GEJ) adenocarcinoma who previously followed a trastuzumab (Herceptin)-based regimen 

: Patients with unresectable or metastatic HER2-positive breast cancer who previously followed an anti–HER2-based regimen either in the metastatic setting or the neoadjuvant/adjuvant setting with disease recurrence during or within 6 months of completing therapy 

: Patients with unresectable or metastatic HER2-low breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy 

: Patients with unresectable or metastatic non–small cell lung cancer (NSCLC) with tumors harboring HER2-mutation, as determined by FDA approved test


The DESTINY-Breast03 trial (NCT03529110) results supported the use of trastuzumab deruxtecan instead of ado-trastuzumab emtansine (T-DM1; Kadcyla) for patients with HER2-positive metastatic breast cancer who had already received trastuzumab (Herceptin) and a taxane. This was a phase 3 multicenter, randomly assigned trial. The investigators found that trastuzumab deruxtecan led to lower risk of disease progression or death.

 The DESTINY-Gastric01 trial (NCT03329690) was an open label, randomly assigned phase 2 trial that evaluated the use of trastuzumab deruxtecan vs traditional chemotherapy for patients with HER2-positive advanced gastric cancers. The study results showed significant improvements in response and overall survival.

The DESTINY-Breast01 trial (NCT03248492) studied the effectiveness of trastuzumab deruxtecan in patients previously treated for HER2-positive breast cancer. It was a phase 2 singlearm study that demonstrated good results from trastuzumab deruxtecan in this population, with durable antitumor activity.

The DESTINY-Breast04 trial (NCT03734029) evaluated outcomes for patients with HER2-low metastatic breast cancer defined as immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization negative. Patients treated with trastuzumab deruxtecan had improved progression-free survival vs physician’s choice chemotherapy in the primary efficacy population and across subgroups.

The DESTINY-Lung02 (NCT04644237) assessed the antibodydrug conjugate in patients with previously treated patients with HER2-mutated unresectable or metastatic NSCLC. The overall response rate was 57.7% (95% CI, 43.2%-71.3%).

Trastuzumab deruxtecan is a HER2-directed antibody and topoisomerase inhibitor conjugate composed of 3 components: a HER2-directed monoclonal antibody, a topoisomerase I inhibitor payload, and a tumor-selective cleavable linker. After it binds to HER2 on the tumor cells, trastuzumab deruxtecan undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Once released, the membrane-permeable deruxtecan causes DNA damage and apoptotic cell death.

Trastuzumab deruxtecan is administered once every 3 weeks. Initial administration of trastuzumab deruxtecan is 90 minutes. If tolerated, subsequent infusion is 30 minutes.

Before initial infusion, baseline vital signs, nursing assessment, complete blood count (CBC) results, comprehensive metabolic panel results, pregnancy level, and echocardiogram results must be obtained. CBC is repeated every cycle to monitor for neutropenia, and the echocardiogram is repeated per institutional policy to monitor for left ventricular dysfunction or as clinically indicated. 

At Rutgers Cancer Institute of New Jersey in New Brunswick, in addition to physical assessment and patient account, respiratory status is evaluated before each infusion of trastuzumab deruxtecan using a 6-minute walk test with pulse oximetry monitored prior to ambulation and at completion. Safe handling of trastuzumab deruxtecan includes donning 2 pairs of chemotherapy-approved gloves and disposable gown per Oncology Nursing Society guidelines.

During initial infusion, patient is instructed to report any acute symptoms of hypersensitivity such as sudden difficulty breathing, facial flushing, itchiness, hives, lower back pain, and chest pain. If a hypersensitivity reaction is noted, trastuzumab deruxtecan administration should be immediately stopped and emergency drugs such as diphenhydramine, famotidine, and dexamethasone administered as per institution policy.

Trastuzumab deruxtecan must be protected from light and administered via intravenous line or a central line such as port-a-cath.

Patients treated in the outpatient setting and their family members should be aware of how to reach their health care team in the event of adverse effects and be taught to go to the emergency department in the event of a life-threatening emergency. Patients receiving trastuzumab deruxtecan should be aware of its most common adverse effects, including nausea, vomiting, fatigue, and alopecia. Nurses should make sure patients have antiemetics readily available at home and know how to take them if needed. Focus of instruction should be on the most serious adverse effects related to trastuzumab deruxtecan, including interstitial lung disease and pneumonitis. Patients should be aware of their baseline respiratory status and understand that if they begin coughing more or develop new or worsening breathing problems, they must reach out to the care team. Also, patients should know cardiac issues can occur with trastuzumab deruxtecan, which is why the health care team will obtain baseline echocardiogram results. However, any new or worsening swelling in the lower extremities, heart palpitations, extreme fatigue, dizziness, and worsening shortness of breath should be reported. Furthermore, patients should be educated on the increased risk for neutropenia with trastuzumab deruxtecan and notify their provider if they develop any symptoms of infection.

1. Enhertu. Prescribing information. Daiichi Sankyo Inc; 2022. Accessed July 21, 2022. bit.ly/3vQaR5j 

2. Cortés J, Kim SB, Chung WP, et al; DESTINY-Breast03 Trial Investigators. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386(12):1143-1154. doi:10.1056/nejmoa2115022 

3. Shitara K, Bang YJ, Iwasa S, et al; DESTINY-Gastric01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382(25):2419-2430. doi:10.1056/nejmoa2004413 

4. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382(7):610-621. doi:10.1056/nejmoa1914510 

5. Modi S, Jacot W, Yamashita T, et al; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690 

6. Toolkit for safe handling of hazardous drugs for nurses in oncology. Oncology Nursing Society. 2018. Accessed July 21, 2022. bit. ly/3RRPXw9

After demonstrating significant efficacy as a third-line treatment for patients with metastatic HER2-positive breast cancer, fam-trastuzumab deruxtecan-nxki has gained approval from the FDA for 5 indications and is under investigation across solid tumors. 

Oncology Drug Crash Course: Fam-Trastuzumab Deruxtecan-Nxki (Enhertu)

A quality improvement project based out of Kaiser Permanente San Francisco demonstrated that the median time between pathologic diagnosis to next-generation sequencing (NGS) could be reduced for patients with newly diagnosed metastatic non–small cell lung cancer (NSCLC), according to findings published in 

Investigators assessed processing systems, and following intervention, the median time between diagnosis and receipt of NGS results decreased from 24 days to 16 days. Specifically, the median time between receiving biopsy results to ordering NGS was cut from 7 days to 1 day, whereas the time needed for the specimen to travel between pathology and the NGS vendor remained a median of 6 days both pre- and post-intervention. Because of the intervention, the total time between pathologic diagnosis and appropriate treatment was condensed from 33 days to 22 days. For patients with actionable mutations, the median time from biopsy results to first-line targeted therapy was improved from 28 days to 22 days.

“Molecular testing is an increasingly essential step in the evaluation of a patient with newly diagnosed metastatic NSCLC given [the] prognostic and predictive implications [of the results],” wrote Stephanie Ossowski, MD, MPH, of the Kaiser Permanente San Diego Medical Center, and co-investigators. “By assessing NGS processing through a systems method, turnaround time can be reduced by interdepartmental communication, automated technology, and inviting key stakeholders, including external vendors, to the discussion.”

Testing for driver mutations is an important step in informing first-line treatment decisions. NGS platforms are preferable because they have a greater sensitivity for clinically relevant gene alterations.

Unfortunately, NGS platforms, despite being more sensitive in detecting actionable mutations, require longer turnaround times than non-NGS testing options. Although in NSCLC, there is little evidence documenting a relationship between time to treatment and patient outcomes, delays in treatment times have been shown to negatively affect survival outcomes in early-stage breast, lung, and colon cancers, underscoring the value of condensing time to molecular testing.

For this quality improvement project, investigators included 42 adult patients who were being seen by a medical oncologist in either an inpatient or outpatient setting associated with Kaiser Permanente San Francisco between December 2018 and August 2021. Investigators collaborated with pathologists, medical oncologists, research partners, technology leaders, and tissue NGS vendors.

The intervention’s main crux was physician review of pathology results for newly diagnosed patients. Prior to the intervention, initial results were sent first to the patients’ primary care doctors and then to the medical oncologist. Typically, the oncologist would not see the pathology results or order NGS until they had their first visit with the patient. To address this delay, investigators collaborated with the authors of the CoPath system, a pathology information system created by Cerner, to develop an automated weekly report of newly diagnosed cases of metastatic NSCLC. Each week, physicians would review the cases and place orders for patients with confirmed metastatic disease, effectively cutting down the time to ordering NGS by a median of 6 days.

In addition, investigators negotiated with their preferred NGS vendor to allow specimens to be accepted 7 days a week. Prior to this negotiation, NGS specimens could only be accepted Monday through Thursday. With this negation, the pathology department could now send out specimens to the NGS vendor during each weekday.

For those included in the quality improvement project, the median age was 68 years in the preintervention group and 76 years in the postintervention group. Smoking histories were similar between the 2 groups. In the preintervention group, 56% of patients had actionable mutations, whereas in the postintervention group, 61% of patients had actionable mutations. All included patients received NGS testing.

Study authors noted that in the process of implementing this project, it became apparent that ordering NGS is a complex process with multiple interdepartmental handoffs. Standard practice did not have oncologists accessing pathology results or ordering NGS testing until their first visit with the patient. After these tests were ordered, both the regional and local pathology departments would sequentially process the specimen, and the division of research was responsible for reviewing the order and facilitating communication with the NGS vendor.

However, through reviewing the institutional system flowchart, it was determined that reducing time to NGS order and increasing specimen acceptance with the NGS vendor represented low-effort, high-yield, opportunities for improvement. Following implementation, the median time between biopsy results and NGS order was reduced from 7 days to 1 days.

For many community practices such as Kaiser Permanente San Francisco, which is part of a large delivery system comprised over 21 cancer centers across Northern California, collaboration with a third party NGS vendor is a standard approach to molecular testing.However, study authors noted that a standardized turnaround time for issue NGS processing has yet to be fully established. This project, and its results, demonstrate how complex NGS processing can be in a community practice setting.

“A formal process is needed to identify barriers, and a team-based approach is required to solve it,” study authors concluded. “By decreasing handoffs and increasing communication between departments and external vendors, processing time for tissue NGS can be reduced in an integrated health care system.”

Ossowski S, Neeman E, Borden C, et al. Improving time to molecular testing results in patients with newly diagnosed, metastatic non-small-cell lung cancer. 

. Published online October 3, 2022. doi:10.1200/OP.22.00260

Drilon A, Wang L, Arcila ME, et al. Broad, hybrid capture-based next-generation sequencing identifies actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches. 

. 2015;21(16):3631-3639. doi:10.1158/1078-0432.CCR-14-2683

A quality improvement project improved the time to molecular testing for patients with newly diagnosed, metastatic non–small cell lung cancer.

Novel Intervention Reduces Time to Molecular Testing for Patients With NSCLC In Community Practice Setting

The addition of the PD-L1 inhibitor sintilimab to pemetrexed (Alimta) and cisplatin led to significant improvements in progression-free survival (PFS) among patients with advanced, 

-mutant non–small cell lung cancer (NSCLC) who had previously been treated with EGFR TKI therapy. The data from a second interim analysis of the phase 3 ORIENT-31 trial (NCT03802240) were presented at the 2022 ESMO Congress.


At a median follow-up of 13.1 months, the median PFS was 5.5 months (95% CI, 4.5-6.1) with sintilimab plus chemotherapy vs 4.3 months (95% CI, 4.1-5.3) with placebo plus chemotherapy (HR, 0.72; 95% CI, 0.55-0.95; 

“This is the first randomized, double-blind, placebo-controlled study that indicates significant PFS benefit with platinum-based doublet chemotherapy plus [an] anti–PD-1 antibody with or without [a] VEGF inhibitor vs chemotherapy alone,” lead study author Shun Lu, MD, PhD, of Shanghai Chest Hospital in China, and coauthors, wrote in a presentation.

Treatment options remain poor for patients with advanced 

-mutant NSCLC who have progressed on EGFR TKIs.

The double-blind, multicenter trial evaluated sintilimab, with or without the bevacizumab (Avastin) biosimilar IBI305 plus chemotherapy in patients between the ages of 18 and 75 years who had received a diagnosis of histologically or cytologically confirmed, unresectable advanced or metastatic nonsquamous NSCLC. Patients needed to have an 

-mutated tumor, resistance to an EGFR TKI, no prior systemic therapy, and asymptomatic or stable brain metastases.

Patients were randomly assigned to 1 of 3 arms: 200 mg of intravenous sintilimab plus 15 mg/kg of the biosimilar, 75 mg/m

 of pemetrexed every 3 weeks (arm A; n = 160); sintilimab plus pemetrexed, cisplatin, and placebo every 3 weeks (arm B; n = 160); or pemetrexed and cisplatin plus 2 placebos every 3 weeks (arm C; n = 160). All patients received 4 cycles of therapy before continuing to maintenance therapy.

Patients were stratified based on gender (male vs female) and whether brain metastases were present (yes vs no).

PFS comparing arms A and C and arms B and C served as the primary end point. Secondary end points included overall survival (OS), overall response rate (ORR), disease control rate (DCR), and duration of response (DOR).

Findings from the first interim analysis demonstrated a significant improvement in PFS in arm A vs arm C (HR, 0.46; 95% CI, 0.34-0.64; 

The data cutoff for the second interim analysis was March 31, 2022. The 2-sided superiority boundary for arm B vs arm C was an alpha of 0.0444.

The median age of patients in arm B was 57.5 years (range, 33-78) vs 56.0 years (range, 30-75) in arm C; 41.1% and 40.0% of patients, respectively, were male, and 36.7% vs 36.9%, respectively, had brain metastases. Moreover, 26.8% of those in arm B and 27.2% of those in arm C had T790M mutation positivity.

Additional results demonstrated improved ORR, DCR, and DOR with sintilimab. In arm B, the ORR was 34.8% (95% CI, 27.4%-42.8%) vs 29.4% (95% CI, 22.4%-37.1%) in arm C, translating to a rate difference of 5.3% (95% CI, -5.0% to 15.5%). The DCR was 81.6% (95% CI, 74.7%-87.3%) in arm B vs 75.6% (95% CI, 68.2%-82.1%) in arm C. The median DOR in arms A and B was 7.4 months (95% CI, 4.7-12.0) and 5.7 months (95% CI, 4.1-7.1), respectively.

Moreover, most subgroups benefitted from the addition of sintilimab, with the exception of patients with T790M mutations (HR, 1.10; 95% CI, 0.68-1.79) and those who received 2 lines of prior EGFR TKI therapy (HR, 1.30; 95% CI, 0.80-2.10).

The OS data were immature at the time of the second interim analysis.

Regarding safety, any-grade treatment-emergent adverse effects (TEAEs) were comparable between the arms, occurring in 96.8% of those in arm B vs 99.4% of those in arm C. Grade 3 or greater TEAEs were lower in arm B vs arm C, at 46.2% and 56.9%, respectively. The rates of serious events and those leading to death were also lower in arm B, at 26.3% and 1.3%, respectively, vs 30.6% and 3.1%, respectively, in arm C.

“The safety profile was acceptable without new unexpected safety signals,” the authors wrote.

Common toxicities in order of frequency included anemia, neutrophil count decrease, white blood cell count decrease, nausea, decreased appetite, asthenia, aspartate aminotransferase increase, vomiting, alanine aminotransferase increase, constipation, platelet count decrease, hypertension, weight decrease, blood creatinine increase, gamma-glutamyltransferase increase, and proteinuria.

Effects that led to treatment discontinuation occurred in 10.3% of patients in arm B vs 6.9% of those in arm C. Immune-related events occurred more commonly in arm B than arm C, at 26.3% and 15.6%, respectively.

Lu S, Wu L, Jian H, et al. Sintilimab with or without IBI305 plus chemotherapy in patients with EGFR mutated non-squamous non-small-cell lung cancer (EGFRm nsqNSCLC) who progressed on EGFR tyrosine-kinase inhibitors (TKIs) therapy: second interim analysis of phase 3 ORIENT-31 study. 

. 2022;33(suppl 7):S1424. doi:10.1016/j.annonc.2022.08.060

Lu S, Wu L, Jian H, et al. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. 

. 2022;23(9):1167-1179. doi:10.1016/S1470-2045(22)00382-5

After 13.1 months of follow-up, the median progression-free survival in patients with EGFR-mutant non–small cell lung cancer who received a sintilimab-based regimen was 5.5 months. 

Sintilimab/Chemotherapy Regimen Boosts Progression-Free Survival in EGFR-Mutated NSCLC

Transformative solutions in nursing are ones that are sustainable, according to Linda Laskowski-Jones, MS, APRN, ACNS-BC, CEN, NEA-BC, FAAN. To come up with a transformative solution, leaders need to engage their employees and see how new strategies affect their working environment.

“Transformation oftentimes [is a] term bantered about and used freely in healthcare institutions today across the board but without understanding what it means, what it looks like, and how much time it takes—because it's not a short walk,” Laskowski-Jones said. She added, “as an oncology nurse, I think you can advocate best through helping to enable others to grow and when you do that you grow yourself and you also learn to take risks in your profession.”

®, Laskowski-Jones, who is editor-in-chief of 

 and president of the Delaware Emergency Nurses Association, and who has spent nearly 4 decades working in trauma and emergency nursing, as well as served as a manager, director and vice president in her hospital’s trauma and emergency departments, discussed how meeting problems with transformative solutions can help improve the working conditions of nurses across a unit.

Understanding the problem: Nursing Shortages

In her presentation, Laskowski-Jones highlighted that, although there are 4.3 million nurses in the US, because of new roles, more jobs, retirements, better staffing ratios, and RN’s leaving the profession, 11 million more nurses are needed to avoid shortages. Moreover, RN employment is projected to be the occupation requiring the most growth through 2026.

The effect of the COVID-19 pandemic on the nursing landscape paired with outside pressures as well as internal elements such as workloads, expectations, and patient factors, have left the field needing transformative solutions to address the causes of turnover along with burnout. Based on geography and specialty, the average turnover of nursing staff ranges from 8.8% to 37% and the American Nurses Association declared the nursing shortage a national crisis on September 1, 2021, to the Department of Health and Human Services.

In speaking about the nursing shortage, Laskowski-Jones noted that the “great resignation” had already begun in 2019, before the COVID-19 pandemic. “In 2019 there was this uptake of resignations across the board in all professions—not just in healthcare…. hospitals were starting to ratchet down on staffing. They were trying to cut corners and reduce resource utilization, [even though] we had organizations saying: we expect high patient experience scores.”

Laskowski-Jones noted that hospitals were being held to higher standards as the patient experience scores are publicly reported and with that came pressure. Additionally, an increase of violence in health care, and lawsuits piled on.

Of course, in 2020, the pandemic compounded these issues, and by 2021, many nurses were burnt out.

“In 2020, we had the pandemic, and everybody was engaged because nurses rise to the challenges, we always rise to the challenges, they’re all in; they’re being battered with what they’re dealing with between the personal protective equipment needs, the complex patients, potentially being pulled to a unit where they never worked before, having to learn new skills, and dealing with devastating situations in many cases,” Laskowski-Jones said.

“[However,] 2021 was a different story,” she said. “Even with vaccines, the pandemic had not ended. The biggest thing was that there was this latent demand in the community for services [because some patient’s] cancer wasn't diagnosed or their heart disease wasn't diagnosed and now they were all coming in where they had been too afraid to even use the hospital [before].” 

With a large increase in patients coming to hospitals, nurses were working in environments that were at overcapacity and nurses “did not feel that they were being supported, they were valued, and they were starting to see shortages that weren't necessarily being addressed.”

While issues were still active, travel nurses had a large positive affect in care, but this impacted the dynamic in the hospital as travel nurses receive high contract pay which may have led some nurses who had been at institutions for a long time to feel undervalued and leave.

In her presentation, Laskowski-Jones noted that creating a healthy workplace environment is a crucial solution in beginning to rebuild the nursing field. The root causes for burnout, turnover and unhappiness must be addressed, and nurses should not be expected to be able to handle everything with a lack of support; psychological safety must be developed. Key points under that umbrella include developing non-defensive listening skills, promoting a clear vision with team alignment, innovation, respectful communication, and generating a culture across the organization of effective teamwork.

Transformative is a broad term, but it essentially refers to solutions that are sustainable, according to Laskowski-Jones. She highlighted some examples of unsustainable solutions vs sustainable ones.

“Transformation means going from this vision of what you think should be to sustainably getting there.” Laskowski-Jones gave the example, “let’s say there is a directive that when the patient comes in staff have only a specified amount of time to get a certain type of work done (eg, their admission process, or their discharge process, etc.).

In this hypothetical example, Laskowski-Jones said, someone looked at data and determined that all patients should be discharged in 6 hours. All nurses are trying to get patients discharged within a 6-hour time-frame. However, if they are struggling to do it, are exhausted, and are consequently cutting corners, that would be an unsustainable goal as currently performed.

Sustainable solutions should make work easier and more effective, Laskowski-Jones noted. This means that when new strategies are implemented, leaders should be asking employees how they feel about the change, and whether it is making things better.

Laskowski-Jones’s presentation emphasized the importance of creating a healthy work culture and assessing one’s own style and reputation to encourage positive change in the environment. Emotional intelligence is key in the workplace and establishing trust to build relationships with coworkers and teams is crucial while being mindful of short- and long-term goals that are set.

When discussing issues in the workplace, Laskowski-Jones said that she encourages nurses to come-up with solutions to the problems that they pose to her.

“If you bring me a problem,” she said, “and I don’t care what it is, you need to bring me your idea of what the solution is... If we make this change that you recommend, how is that going to affect other people?”

Lastly, Laskowski-Jones emphasized that leadership must value their staff.

“You have to show empathy,” she said. “Value is not just giving somebody a little gift… or some sort of recognition day, value is being able to have a conversation where you witnessed someone having a difficult day or a challenging patient,” she said. “It’s when a manager says ‘I was impressed with how you handled that.’ Or that must have been difficult for you, do you want to talk about it? I am here to listen, I’ve been there, and I know how hard this is.” 

Laskowski-Jones L. Finding your voice: how nurses can create a healthy work culture to enhance a thriving work environment. Presented at: ONS Bridge; September 13-15, 2022; virtual.

Linda Laskowski-Jones, MS, APRN, ACNS-BC, CEN, NEA-BC, FAAN, discusses how oncology nurse leaders can help improve working environments for their staff. 

Nurse Leaders Must Foster Change to Develop a Healthy Workplace Environment

Favorable objective responses were observed among patients with 

Selpercatinib demonstrated a promising efficacy profile in patients with RET-fusion positive solid tumors. 

Lung Cancer