There are currently a variety of treatment options for patients with renal cell carcinoma—spanning from active surveillance for low-volume or indolent disease, to cytoreductive nephrectomy for diseases that have more favorable outcomes, as well as with immune-oncology (IO) agents or tyrosine kinase inhibitors (TKI) alone or in combination in advanced stages. However, determining the best treatment option for a newly diagnosed patient involves determining their risk stratification, according to Primo Nery Lara Jr, MD.

 Interdisciplinary Prostate Cancer Congress® and Other Genitourinary Malignancies, Lara, who is director of the University of California Davis (UC Davis) Comprehensive Cancer Center as well as Codman-Radke Endowed Chair in Cancer Research and executive associate dean for Cancer Programs at UC Davis Health in Sacramento, provided an overview of the treatment landscape for patients with metastatic RCC.

A key feature to developing treatment pathways that involve risk stratification according to International Metastatic RCC Database Consortium (IMDC) criteria is to leverage a multidisciplinary tumor board. “The [first] question that the tumor board tackles is whether an individual with metastatic RCC is a candidate for active surveillance.” Lara said.

From that point, several options are available including cytoreduction and combination immunotherapy-based therapy which is the standard of care for most patients.

IO Eligibility: Choosing the Right Treatment Path

With numerous approved combination regimens, including dual IO therapies and IO/TKI combinations, Lara noted that strategies for choosing between regimens goes beyond eligibility and relies on risk stratification. “The standard of care in 2022 for metastatic kidney cancer is immunotherapy-based combination therapy,” Lara said. “Most of these patients should be considered for combination therapies, and there are several combinations that we would offer depending on their risk group.”

If a patient is deemed eligible for an IO-based combination, patients with favorable-risk, intermediate-risk, and poor-risk disease have several options available including pembrolizumab (Keytruda) in combination with either axitinib (Inlyta) or lanvantanib (Lenvima), nivolumab (Opdivo) plus cabozantinib (Cabometyx), or avelumab (Bavencio) plus axitinib.

For those with intermediate- or poor-risk disease, Lara noted that the immunotherapy doublet of nivolumab plus ipilimumab (Yervoy) is the preferred treatment option, noting that the combination does not improve outcomes over sunitinib (Sutent) alone for those with favorable-risk disease.

Four-year follow-up data from the phase 3 CheckMate 214 trial (NCT02231749), which led to the approval of nivolumab (Opdivo) plus ipilimumab (Yervoy) in patients with frontline metastatic RCC, show advantage of the combination vs sunitinib in terms of OS for the intention-to-treat population (HR, 0.69; 95% CI, 0.59-0.81) and the intermediate/poor-risk subgroup (HR, 0.65; 95% CI, 0.54-0.78).

 Patients with favorable-risk disease failed to derive an OS benefit (HR, 0.93; 0.62-1.40).

“[This combination] would be great for intermediate- and poor-risk disease, not so much for favorable risk where it was no better than sunitinib,” Lara said

Despite being recommended for all-risk groups, Lara noted that, most of the benefit with pembrolizumab/axitinib in the phase 3 KEYNOTE-426 trial (NCT02853331) was isolated to patients with intermediate/poor-risk disease. Updated data at the 42-month follow-up showed sustained OS benefit of the combination (HR, 0.73; 95% CI, 0.60-0.88; 

< .001) vs sunitinib in the intention-to-treat population.

 The benefit was more prominent in the progression-free survival (PFS) analysis with a median PFS of 15.7 months (95% CI, 13.6-20.2) with the combination vs 11.1 months (95% CI, 8.9-12.5) with sunitinib (HR, 0.68; 95% CI, 0.58-0.80; 

In terms of the other recommended therapies, Lara highlighted the advantage of the IO combinations vs single-agent TKI for patients with all-risk disease who are eligible for this treatment pathway. In data from the phase 3 CheckMate 9ER trial (NCT03141177), which supported the approval of cabozantinib and nivolumab in this setting, Lara spotlighted OS results which showed a 40% reduction in the risk of death with the combination vs sunitnib (HR, 0.60; 98.89% CI, 0.40-0.89; 

Finally, the phase 3 CLEAR trial (NCT02811861) showed an advantage of lenvatinib plus pembrolizumab vs sunitinib in terms of PFS (HR, 0.39; 95% CI, 0.32-0.49; 

 < .001) and OS (HR, 0.66; 95% CI, 0.49-0.88; 

Comparing results of CLEAR with the previously reviewed trials, Lara said “results superficially seem to be better if you look at the complete response rate, the median PFS, and [OS]. But you must note that this trial had the lowest percentage of poor-risk patients [vs other pivotal trials reviewed], which will drive a lot of the of the results of these trials.”

Patients who undergo risk stratification and are not eligible for IO therapy, TKIs including sunitinib or pazopanib are preferred treatment options for those with favorable-risk disease. OS outcomes for patients with favorable-risk disease had a median survival time of 37 month with sunitinib vs 9.4 months among those with poor-risk disease.

“Those who have active autoimmune disease should probably not risk [treatment with] a checkpoint inhibitor. Those with a history of solid organ transplantation and those on supraphysiologic corticosteroids are not your best candidates, or those with illnesses that require chronic immune suppressive therapy,” Lara said. “Sometimes there will be a patient who will have a personal preference [to avoid intravenous] therapy or who doesn’t want to go to your clinic because it is too far to drive; they’re not eligible for immunotherapy for those practical reasons.”

In patients with bone-only metastases, cabozantinib monotherapy may be preferential based on results of the phase 1 CABOSUN trial (NCT02496208), which showed a PFS advantage vs sunitinib in the indicated patient subset (0.54; 95% CI, 0.31-0.95).

 Similarly, Lara said he would use single-agent cabozantinib for patients with non–clear cell papillary RCC and perhaps for those with favorable-risk disease.

“Favorable-risk patients treated with pembrolizumab plus axitinib didn’t seem to benefit from that doublet, so maybe those patients ought to get a VEGFR TKI and then reserved immunotherapy for later,” Lara said.

Conversely, some patients may only be suitable for treatment with single-agent immunotherapy. “For those who are ineligible for or refuse to receive a VEGFR TKI–containing combination or those patients who [want to avoid] ipilimumab toxicities, single-agent checkpoint inhibitors are reasonable.” However, Lara noted that this should be limited to few patients with single-agent HD IL-2 and mTOR inhibitors representing 2 treatment options that have little justification for use in an era or more active, life-prolonging therapies.

Other branches of the decision tree for patients with metastatic RCC include active surveillance and cytoreduction for patients with favorable-risk disease.

“There is a subset of patients with advanced kidney cancer for whom you could watch [and wait] until such time comes when you do need to treat them with systemic therapies that have adverse effects. The question of who is a candidate for active surveillance is hard to answer because this is a bedside, gut decision.”

Lara reviewed data from a phase 2 prospective trial of 52 patients that showed surveillance could be a viable treatment option for certain patients with metastatic RCC.

 Median time to treatment initiation was 14.9 months (95% CI, 10.6-25.0) overall, with shortened surveillance associated with adverse risk factors (

 = .0403) and higher numbers of metastatic disease sites (

“The other question that tumor boards often tackle is whether a cytoreductive approach is necessary,” Lara said. “Most favorable-risk patients and some of those with intermediate-risk disease remain candidates for a cytoreductive nephrectomy, especially those with large and/or symptomatic primary tumors and a low burden of metastatic disease.”

Recently reported data from 2 trials showed noninferiority of systemic therapy approaches vs systemic therapy plus nephrectomy in this setting. In the phase 3 CARMENA trial (NCT00930033), sunitinib alone was found to produce noninferior overall survival (OS) vs sunitinib plus nephrectomy in patients with intermediate- or poor-risk disease (HR, 0.89; 95% CI, 0.71-1.10).

 In the phase 3 SURTIME trial (NCT01099423), deferred cytoreductive nephrectomy after 3 cycles of sunitinib improved OS vs immediate nephrectomy (HR, 0.57; 95% CI, 0.34-0.95; 

 He noted that decisions must be individualized according to risk.

“Many intermediate- and most poor-risk patients should start on systemic therapy first,” Lara said.

As for metastasectomy, Lara said patients with a good performance status, isolated or oligometastatic disease, a disease-free interval of 2 years following nephrectomy, no lymph node involvement, or lung-only disease may benefit from local ablative approaches.

Lara P. Frontline systemic therapy for renal cell carcinoma: immunotherapy and tyrosine kinase inhibitors. Presented at: 

 Interdisciplinary Prostate Cancer® and other GU Malignancies Congress. March 11-12, 2022. New York, NY.

FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma. FDA. April 16, 2018. Accessed March 14, 2022. bit.ly/3Jji5nm

Albiges L, Tannir NM, Burotto M, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. 

. 2020;5(6):e001079. doi:10.1136/esmoopen-2020-001079

Rini BI, Plimack ER, Stus V, et al. Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Results from 42-month follow-up of KEYNOTE-426. 

. 2021;39(suppl 15):4500. doi:10.1200/JCO.2021.39.15_suppl.4500

FDA approves nivolumab plus cabozantinib for advanced renal cell carcinoma. FDA. January 22, 2021. Accessed March 14, 2022. https://bit.ly/34Gb3K4

Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. 

. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716

Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the Alliance A031203 CABOSUN trial. 

. 2017;35(6):591-597. doi:10.1200/JCO.2016.70.7398

Rini BI, Dorff TB, Elson P, et al. Active surveillance in metastatic renal-cell carcinoma: a prospective, phase 2 trial. 

. 2016;17(9):1317-1324. doi:10.1016/S1470-2045(16)30196-6

Méjean A, Ravaud A, Thezenas S, et al. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. 

. 2018;379(5):417-427. doi:10.1056/NEJMoa1803675

Bex A, Mulders P, Jewett M, et al. Comparison of immediate vs deferred cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma receiving sunitinib: the SURTIME randomized clinical trial. 

. 2019;5(2):164-170. doi:10.1001/jamaoncol.2018.5543

This article was originally published on OncLive as “Navigating Frontline RCC Treatment Paths Relies on Risk Stratification”

Articles

Patients with metastatic renal cell carcinoma have multiple effective frontline treatment options. 

Effective Frontline RCC Treatment Navigation Is Tied to Risk Stratification

Responses from Black and Hispanic patients with hormone receptor (HR)–positive, HER2-negative advanced breast cancer who received palbociclib (Ibrance) plus endocrine therapy were consistent with outcomes seen in overall study populations, supporting the continued use of this combination among this patient population, according to a pooled efficacy and safety analysis presented at the 2021 San Antonio Breast Cancer Symposium (SABCS).

The relatively small proportion of Black and Hispanic patients in key clinical trials that led to the approval of palbociclib across multiple indications in advanced breast cancer motivated the research team to look further at this population.

“This post-hoc analysis of the PALOMA trials evaluated the efficacy and safety of palbociclib plus endocrine therapy in Black and Hispanic patients,” Claudine Isaacs, MD, professor of medicine and oncology and Clinical Breast Cancer Program Lead at Lombardi Comprehensive Cancer Center at Georgetown University, said in a recorded presentation of the findings. “Approximately 10% of the PALOMA-2 and PALOMA-3 patient populations self-identified as Black or Hispanic.”

Previously reported data from the placebo-controlled, phase 3 PALOMA-2 (NCT01740427) and PALOMA-3 (NCT01942135) clinical trials, which served as the efficacy analysis for this dataset, demonstrated a significant improvement in median progression-free survival (PFS) with a manageable safety profile when patients were treated with a palbociclib-containing regimen. The safety analysis also included data from the phase 2 PALOMA-1 trial (NCT00721409).

In PALOMA-1 and PALOMA-2, postmenopausal patients received palbociclib plus letrozole vs letrozole alone or with placebo, respectively, as frontline treatment for HR-positive, HER2-negative advanced breast cancer. In PALOMA-3, pre- or postmenopausal patients with disease progression after endocrine therapy were treated with fulvestrant (Faslodex) and either placebo or palbociclib.

The median PFS in 65 self-identified Black or Hispanic patients treated on PALOMA-2 was 27.4 months vs 13.8 months for the palbociclib and placebo arms, respectively (HR, 0.61; 95% CI, 0.31-1.20). In the 48 self-identified Black or Hispanic patients treated on PALOMA-3, corresponding medians were 11.1 and 1.9 months, respectively (HR, 0.56; 95% CI, 0.28-1.14).

Overall survival results were available for the patients treated on the PALOMA-3 trial, showing a greater benefit with palbociclib at 35.6 months vs 21.0 months with placebo (HR, 0.48; 95% CI, 0.23-0.97).

The safety analysis of all 3 trials revealed a toxicity profile for 120 self-identified Black and Hispanic patients that was consistent with previously reported data in the intention-to-treat (ITT) population. The most common grade 3/4 hematologic adverse effects (AEs) were neutropenia (57.7%), leukopenia (24.4%), and anemia (3.8%), which were all similar to the rates in the overall population (65.4%, 26.7%, and 4.6%, respectively).

All-grade non-hematologic AEs in the intent-to-treat (ITT) and subgroup analysis included infections (50.0% vs 54.7%, respectively), fatigue (39.7% vs 39.2%), nausea (38.5% vs 34.2%), constipation (30.8% vs 19.2%), arthralgia (29.5% vs 25.6%), cough (26.9% vs 21.6%), stomatitis (17.9% vs 28.9%), and alopecia (16.7% vs 25.9%).

Dose reductions resulting from AEs occurred in 37.2% of Black and Hispanic patients treated with palbociclib and was similar to the rates observed in the ITT population across all 3 trials (range, 39.4%-42.2%). Dose interruptions or delays occurred in 60.3% of Black and Hispanic patients treated with active therapy, which was slightly lower than the same rate in the ITT population (71.4%).

Patient characteristics were detailed for the PALOMA-2 and PALOMA-3 trials and were well-balanced between groups. Of the 66 self-identified Black or Hispanic patients treated on PALOMA-2, 47 received active therapy and 18 received placebo. Median patients ages were 58 years (range, 35-89) and 54 years (range, 39-67), respectively. More patients treated with palbociclib had visceral disease (61.7% vs 50.0%), lung involvement (51.1% vs 22.2%), and de novo disease (44.7% vs 22.2%) whereas fewer had received prior systemic therapy (55.3% vs 77.8%) than those in the placebo group. Of the 48 self-identified Black or Hispanic patients treated on PALOMA-3, 29 received active therapy and 19 received placebo; median patient age was 57 years in both groups.

Palbociclib is a first-in-class CDK4/6 inhibitor approved for use in combination with an aromatase inhibitor or fulvestrant in patients with hormone receptor–positive, HER2-negative advanced breast cancer.

“These findings support the continued use of palbociclib plus endocrine therapy for women hormone receptor–positive, HER2-negative advanced breast cancer in Black and Hispanic patients,” Isaacs concluded.

Isaacs C, Mahtini R, Lynce F, et al. Efficacy and safety of palbociclib plus endocrine therapy in Black and Hispanic patients with hormone receptor positive/human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC) participating in the PALOMA trials. Presented at: San Antonio Breast Cancer Symposium. December 7-10, 2021. San Antonio, TX. Abstract P1-18-13.

Findings from a pooled efficacy and safety analysis support the use of palbociclib plus endocrine therapy in patients who are Black or Hispanic with hormone receptor–positive, HER2-negative breast cancer.

Palbociclib Shows Clinical Benefit in Black and Hispanic Patients with HR+ Breast Cancer

Mobocertinib (formerly TAK-788) induced improved patient-reported outcomes (PROs) in patients with previously treated non-small-cell lung cancer (NSCLC) harboring 

 exon 20 insertion mutations, according to a poster presentation of the EXCLAIM extension cohort made available as part of the 2021 World Conference on Lung Cancer.

In patients considered to have difficult-to-treat disease who were treated as part of a phase 1/2 trial (NCT02716116), superior PROs were evidenced by better core NSCLC symptoms within 2 months of treatment initiation which was maintained for the duration of therapy and was consistent with clinical activity.

“Overall health-related quality of life was maintained during therapy, despite the occurrence of adverse events such as rash and gastrointestinal-related symptoms,” Maria Rosario Garcia Campelo, MD, of the University Hospital A Coruña in Spain, said during a presentation of the data.

The objective of the current analysis was to evaluate PROs associated with daily oral mobocertinib at 160 mg daily in the discussed patient population. PRO tools used included the European Organisation for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (EORTC QLQ-C30) for cancer-related functions and symptoms, the European Organisation for Research and Treatment of Cancer Core Quality-of-Life Questionnaire lung cancer module (EORTC QLQ-LC13) for lung cancer–specific symptoms, the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) and visual analogue scale (VAS) for general health-related quality of life, and selected items from Patient-Reported Outcomes–Common Terminology Criteria for Adverse Events Questionnaire (PRO-CTCAE) to assess symptomatic toxicity in these patients. Questionnaires were given prior to clinical evaluation or procedures at baseline, at select visits, and at 30 days following the last dose of treatment.

Compliance rates were above 80% for all instruments and were often above 90% for most cycles. At the data cutoff of November 1, 2020, 25 out of 96 patients (26%) remained on treatment with mobocertinib for a median time of treatment of 6.8 months (range, 0.0-18.8). Median patient age was 59 years (range, 27-80), with most patients being women (65%) and never smokers (73%) and the majority having adenocarcinoma histology (99%) and an ECOG performance status of 1 (71%). The median number of prior therapies was 1, with prior platinum-based chemotherapy accounting for 90% of patients, prior immunotherapy in 34%, and prior 

 inhibitors in 31%. Baseline brain metastases were present in 34% of patients.

Clinically meaningful lung cancer symptom improvement by EORTC QLQ-LC13 was defined as a 10-point or greater decrease in symptom score. At a median follow-up of 13.0 months (range, 0.7-18.8), clinically meaningful changes in dyspnea occurred in 54.4% of patients, with a mean change to baseline symptoms of –3.2 (

 = .019). Cough improved in 46.7% of patients with a mean baseline improvement of –9.3 (

 < .001). For chest pain, improvement occurred in 38.9% of patients with a mean baseline improvement of –8.2 (

 < .001). In over 50% of the patients examined, dyspnea, cough, and chest pain were improved or stable throughout the study.

By EORTC QLQ-C30, baseline scores were maintained or improved in most patients treated with mobocertinib, for a least square mean change of –1.8 (95% CI, –4.8 to 1.2; 

 = .235). By PRO-CTCAE, the majority of adverse effects of were not categorized in the 2 highest categories of “severe” or “very severe”, with only diarrhea and dry skin escalating to above 10% of events being in the highest categories (22.2% and 11.1%, respectively). By EQ-5D VAS, patient-reported general health-related quality of life remained largely stable during treatment. 

Previously reported data from the trial demonstrated efficacy of mobocertinib in this patient population, with a confirmed overall response rate of 28% (95% CI, 20%-37%), a median overall survival of 24.0 months (95% CI, 14.6-28.8), and a median progression-free survival was 7.3 months (95% CI, 5.5-9.2). The mechanism of action of mobocertinib is unique in that it selectively targets exon 20 insertion mutations in EGFR

“Exon 20 insertion mutations account for up to 12% of NSCLC tumors with 

 mutations. Most of these patients are treated in the first line with platinum-based chemotherapy, but their disease, unfortunately, progresses very rapidly,” Campelo said. Use of mobocertinib in these patients may fulfill an unmet clinical need.

Garcia Campelo MR, Zhou C, Ramalingam SS, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion+ metastatic NSCLC: patient-reported outcomes from EXCLAIM extension cohort. Presented at: 2021 World Conference on Lung Cancer; September 8-14, 2021. Virtual. Abstract FP09.02.

Selectively targeting the EGFR exon insertion mutations was associated with improved outcomes in patients with previously treated non-small cell lung cancer. 



Patients Report Improved Outcomes Following Mobocertinib Treatment for NSCLC Subtype

A single-center program for enhancing patient-provider relationships was able to improve staff member’s understanding of adult education, and in turn, positively effect patient satisfaction scores over time, according to data presented in a poster at the Oncology Nursing Society’s 46th Annual Congress.

This program, developed for the Trinitas Comprehensive Cancer Center in Elizabeth, New Jersey, set out to educate nurses, medical assistants, receptionists, and secretarial staff about patient interactions and to assess their needs. The program will continue to be evaluated through attendance to the program and pre- and post-test intervention assessment; program effectiveness valuation will be conducted by patient-satisfaction surveys.

“In our post program [assessment], our staff showed a better understanding of what adult education is all about and how adults view and learn new knowledge,” Aida Brito, MSN, RN, OCN, lead study author, said in her presentation of the data.

The investigators set out to improve the patients experience based on existing data that indicate health care quality and patient satisfaction go hand in hand. The Ask Me 3 tool and the Oral Exchange Rating Tool, Part 3 were used to educate staff about patient interactions. Pre-program learning-needs assessments and tests were used to determine individual perceptions of the role they play in a patient-provider interaction. All staff then attended the program, and a post-test was given to assess understanding of the content.

Staff members included registered nurses, medical assistants, concierges, patient guides, and medical secretaries. A needs assessment showed that clinicians were interested in learning more about quality of life and critical lab values, symptom management and assessment, and ethical issues.

Themes emerging from the Ask Me 3 pre- and post-tests were education, listening, questioning, understanding, and advocacy. The oral exchange rating summary average scores improved from the pre-program assessment at 29 to 58.4 post-program. Brito pointed out that fewer participants were assessed in the post-program (22 vs 16) due to resignations and medical leave.

Patient satisfaction scores improved from the second quarter (Q2) of 2020 through the first quarter (Q1) of 2021 in areas of emotional support and respect for patient preferences. When asked the question: “How often did you have confidence and trust in the cancer treatment staff treating you?” patient satisfaction scores improved from 76.8% in Q2 2020 to 92.6% in Q1 2021. To the question: “How often did the cancer treatment staff treat you with courtesy and respect” scores improved from 89.3% in Q2 2020 to 93.5% in Q4 2020 but were at 89.3% again in Q1 2021. Scores to: “How often did you have enough input or say in your care at this facility?” scores went from 60.4% in Q2 2020 to 74.1% in Q1 2021.

“Once our patient-provider trusting relationship improves this will in turn enhance health care quality thus improving patient experience and satisfaction,” Brito said. “It is our hope that through proper staff education and the use of the Ask Me 3 communication tool, our cancer patient population will feel confident and supported throughout their cancer experience.”

Brito A, Fryar J, Blecher C. Cultivating a patient-provider relationship of trust while enhancing/improving patient experience and satisfaction. Presented at: Oncology Nursing Society 46th Annual Congress. April 20, 22, 27 & 29, 2021. Virtual.

A poster presentation from the Oncology Nursing Society’s 46th Annual Congress describes a single-center clinician education program aimed at improving patient satisfaction.

Cancer Center Seeks to Improve Patient Experience, Satisfaction Through Communication Education With Staff

As the impact of the coronavirus disease 2019 (COVID-19) pandemic lingers into the later part of 2020, consideration is needed regarding the lasting effects on patients with cancer who may have experienced delayed care or diagnosis.

Investigators conducted a survey involving health care representatives from the international oncology community to assess the preliminary effects of the pandemic and highlight major concerns regarding patient care. The results of the survey will be covered in detail during the European Society for Medical Oncology (ESMO) 2020 Virtual Congress.

“Our survey confirms that COVID-19 has a major impact on organization of patient care and on the well-being of caregivers,” Guy Jerusalem, MD, PhD, head of the Breast Unit at Centre Hospitalier Universitaire du Sart-Tilman, Liège, Belgium, said during a presentation at the ESMO 2020 Opening Press Conference. “Clinical trial activity [is also affected], as well as continued medical education.”

Although rapid normalization of professional activities of health care workers was hoped for after the COVID-19 lockdown, it is now clear that there will be long-term impacts of the pandemic. Understanding how these resulting effects influence patients with cancer going forward will be crucial in the coming years.

“When you look into the future, the expected problem is the risk of delayed diagnoses of new cancer,” Jerusalem said. “In our hospitals, we see fewer new patients diagnosed, and the risk is that later we will see more patients with advanced-stage [disease] diagnosed with cancer. The economic consequences of COVID-19, which can affect access to health care and cancer treatments, has to be carefully evaluated.”

To assess the impacts of the pandemic on health care workers, a survey of 109 representatives from 18 countries—including Italy, France, Spain, the United States, Mexico, Brazil, and Argentina&mdash;were compiled. The majority of respondents were men (61.5%) who had a median age of 48.5 years. Most of the respondents worked in an academic (62.4%) or community hospital (29.6%), with a median number of years of worked in the oncology field of 20 (interquartile range, 10.5-25). Those specializing in breast cancer represented the majority of respondents at 60.6%, followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%). Other specialties were included in the survey but represented a low percentage of respondents.

Thirty-four percent of respondents reported that surgery was the treatment modality that was most affected by the pandemic, followed by chemotherapy (22.0%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9.0%), and oral targeted therapy (3.7%).

Treatment adaptations were also noted by those from participating centers, including an increased use of both granulocyte colony—stimulating factor in 34.8% and erythropoietin in 6.4%. Therapy modifications that resulted in a reduction of treatment included decreased use of double immunotherapy in 11.1% of centers and a decrease in corticosteroid use in 21.9%.

Regarding a decrease in the use of corticosteroids, Jerusalem stated that there could be several potential reasons for this observation. “One can be that this is an immunosuppressive agent.

Maybe the risk of infection is increased [with its use],” he posited. “In my center, we had considered [decreasing] the dose of steroids during this time. The question was, ‘Do we increase the risk of infection…if we increase the use of steroids?” He noted that this strategy wasn’t based on any data, but rather a rationale that some centers employed based on what is known of steroid use.

ESMO President Solange Peters, MD, PhD, of University of Lausanne in Switzerland, also commented on this finding, stating that prior steroid use, or being on steroids at the time of COVID-19 infection, has now been associated with worse prognosis and increased mortality, based on findings from the TERVAOLT registry.2 She also stated that steroid use at infection baseline differs significantly from administration of these agents to help fight the virus.

Concerning the care of patients with breast cancer specifically, administration of everolimus (Afinitor) was affected in 18% of centers followed by CDK4/6 inhibitors in 8.9%. Only 2.2% of centers reported that endocrine therapy administration was affected.

Notably, Jerusalem stated that early cessation of anticancer palliative care was observed in nearly one-third of participating centers (32.1%), while nearly two-thirds of participants (64.2%) agreed that the risk of undertreatment, such as early lines of treatment in the metastatic setting, is a major concern.

Telemedicine, or teleconsultations as they were referred to in the presentation, were reportedly performed for 94.5% of follow-up visits and for visits related to oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%). In addition, approximately 82% of participants projected that they would continue with the use of telemedicine more frequently in their practices after the pandemic.

According to the survey results, the effects of the pandemic transcend direct patient care and extended to other areas of life for treating clinicians. Most participants (94%) reported more frequent use of virtual platforms for continued medical education, oncological team meetings (92%), and multidisciplinary tumor boards (82%).

Despite some advantages of holding medical meetings in the virtual format, 45% of those surveyed said that they disagreed with the premise that virtual meetings could serve as an acceptable alternative to live international meetings, such as the ESMO Congress or the American Society of Clinical Oncology Annual Meeting.

Regarding meeting attendance, Peters felt that being pushed to a virtual format for major medical meetings has definite advantages and predicts that organizations will hold on to the positive aspects that resulted from this change. “For every meeting that we had to transform to a virtual format, we first saw a huge increase in the number of attendees and an increase in the geographical span, or the reach, of each conference,” she said. “What you realize is that one of the missions of ESMO, which is being able to convey education globally, was better achieved in the virtual format.”

Peters concluded by stating, “We have to think about how we can communicate…these data and education and fulfill needs in a better way. In the future, we have to do more virtual [meetings].”

1. Jerusalem G. Expected medium and long term impact of the COVID-19 outbreak in oncology. Presented at: European Society for Medical Oncology 2020 Opening Press Conference. September 10, 2020. Virtual. Abstract LBA76_PR.

2. Garassino MC, Whisenant JG, Huang LC, et al. COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study. Lancet Oncol. 2020;21(7):914-922. doi:10.1016/S1470-2045(20)30314-4

This article was originally published on OncLive as, "

Experts Consider Long-Term Impact of COVID-19 Pandemic on Oncology Care

COVID-19 Leaves Its Mark on Cancer Care

In patients with bladder cancer treated with cystectomy, neoadjuvant chemotherapy with a dose-dense, or accelerated, course of methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) was more likely to produce a complete pathologic response (pCR) and extend overall survival (OS) than any other chemotherapy regimen, according to 

Despite published reports on the efficacy of MVAC, gemcitabine plus cisplatin has become the standard neoadjuvant chemotherapy regimen for patients with muscle-invasive 

 preceding surgical resection. This is owing, in part, to its favorable toxicity profile and published clinical trial results showing comparable results between the 2 regimens in patients with metastatic disease.

Regular administration of MVAC has been shown to have a serious toxicity profile with more than 50% of patients experiencing myelosuppression and mucositis in some published reports. However, using a dose-dense administration period is well tolerated, considered safe, and has response rates similar to gemcitabine plus cisplatin.

The investigators, led by Charles C. Peyton, MD, a urologic oncology fellow at Moffitt Cancer Center, performed a retrospective analysis of 1113 patients who underwent cystectomy for bladder cancer at the Moffitt Cancer Center in Tampa, Florida to compare neoadjuvant chemotherapy regimens. Patients undergoing cystectomy who did not receive any type of chemotherapy were included as controls.

Primary outcome measures included pathologic downstaging of disease, defined as either any decrease in disease stage or pCR, and OS, defined as date of cystectomy to date of last follow up or death from any cause. Clinical staging was determined mostly by pathologic findings on resection of the bladder tumor and was supplemented with radiographic images. Time to cystectomy was examined as a secondary outcome across chemotherapy subgroups.

Out of a total of 824 patients with advanced or invasive disease (defined as clinical stage ≥T2N0M0), 332 patients were treated with neoadjuvant chemotherapy, 329 received no chemotherapy, and 163 received induction or adjuvant chemotherapy. In the neoadjuvant chemotherapy group, 204 (61.4%) received gemcitabine plus cisplatin, 46 (14%) received ddMVAC, 32 (10%) received gemcitabine plus carboplatin, and 50 (15.1%) received other agents including etoposide, fluorouracil, and paclitaxel regimens. Standard MVAC was included in the other neoadjuvant chemotherapy regimens group and accounted for 3 patients. A 6- to 8-week administration period was used to distinguish dose-dense from standard MVAC regimens.

Patient characteristics based on chemotherapy regimen were similar between groups. The number of cycles of chemotherapy received were similar across regimens with 146 patients (73.7%) receiving gemcitabine plus cisplatin and 42 (91.3%) receiving ddMVAC having 3 or more cycles of chemotherapy. Clinical-stage distributions were similar between the two groups. Median follow-up times for each group were 15 months (95% CI, 12.6-21.0) for gemcitabine plus cisplatin, 12 months (95% CI, 8.2-19.4) for gemcitabine plus carboplatin, 11 months (95% CI, 6.3-18.0) for ddMVAC, and 15.8 months (95% CI, 12.2-23.6) for patients receiving all other regimens.

Downstaging was observed in 52.2% of patients receiving ddMVAC, 41.3% of patients receiving gemcitabine plus cisplatin, and 27% of patients taking carboplatin plus gemcitabine. The rates of pCR were 41.3%, 24.5%, and 9.4% of patients in each group, respectively. Notably, the rate of pCR for patients without neoadjuvant chemotherapy was 10.7% which is similar to the rate observed in patients receiving neoadjuvant carboplatin plus gemcitabine.

Median OS was higher for patients in the ddMVAC group compared with those treated with other regimens. The 2-year Kaplan-Meier survival probability estimates were 73.3% for ddMVAC (95% CI, 48%-89.1%), 62% for gemcitabine plus cisplatin (95% CI, 53.4%-69.9%), and 34.8% for gemcitabine plus carboplatin (95% CI, 18.8%-55.1%; 

Achieving pCR was also a significant predictor of OS regardless of the chemotherapy agent(s) used. Seventy-eight patients (92.8%) who achieved pCR were still alive 2 years following surgery and these results were consistent across neoadjuvant chemotherapy subgroups. All patients receiving both ddMVAC (n = 19) and gemcitabine plus carboplatin (n = 3) who had achieved pCR were still alive at 2 years. Forty-six patients (92%) receiving gemcitabine plus cisplatin and 10 patients (83.3%) on other chemotherapy regimens who had initially achieved pCR were also alive at 2 years.

Median treatment time for patients taking ddMVAC was 35 days (range 28-46). The average time from the start of neoadjuvant chemotherapy to cystectomy in patients taking ddMVAC was 95 days; for patients taking gemcitabine plus cisplatin the average was 119 days versus 134 days for gemcitabine plus carboplatin (

The most common grade 1/2 adverse event (AE) reported was fatigue in 26 patients taking ddMVAC. There were no grade 4 AEs reported and the toxicity profile reported in this study was consistent with those previously published for ddMVAC.

Trial investigators said adjustments to administering MVAC “have led to better tolerability, and as a result, 3 cycles of neoadjuvant MVAC can be safely and effectively delivered over a 6-week period.”

Peyton CC, Tang D, Reich RR, et al. Downstaging and survival outcomes associated with neoadjuvant chemotherapy regimens among patients treated with cystectomy for muscle-invasive bladder cancer. 

. 2018;4(11):1535-1542. doi: 10.1001/jamaoncol.2018.3542.

This article was originally published on 

Neoadjuvant Dose-Dense MVAC Demonstrates Superior Survival Outcomes in Bladder Cancer

Neoadjuvant chemotherapy with dose-dense MVAC extends overall survival compared with other chemo regimens in bladder cancer treated with cystectomy.

Accelerated Chemo Regimen Extends OS in Neoadjuvant Bladder Cancer Treatment

The addition of tumor treating fields (TTF), an antimitotic therapy that delivers continuous low-intensity electrical fields to the tumor region, to weekly paclitaxel (Taxol) appeared safe in the treatment of patients with platinum-resistant ovarian cancer, according to findings published in 

With a primary endpoint of safety, the INNOVATE (NCT02244502), phase II single-arm trial found no serious adverse events (AEs) from TTF, and investigators said the combination with weekly paclitaxel was well tolerated, with encouraging response and survival data.

Based on these results, investigators will move forward with INNOVATE-3, a prospective open-label study that will randomize 540 patients with recurrent, platinum-resistant ovarian cancer to weekly paclitaxel alone or weekly paclitaxel in combination with TTF tuned to 200 kHz until progression.

Trial eligibility in INNOVATE was based on histologically-confirmed recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. A total of 31 patients were enrolled, median age of 60 years, and 77% (n = 24) had serous histology and stage III disease. All patients had been previously treated with platinum-based chemotherapy, and a majority had also been treated with taxanes (97%), as well as pegylated liposomal doxorubicin (PLD) (58%).

TTF was delivered at 200 kHz in conjunction with paclitaxel administered weekly for 8 weeks and then on days 1, 8, 16 of each subsequent 28 day-cycle, with a starting dose of 80 mg/m

Dermatologic AEs, anticipated from use of TTF, were reported in 28 (90%) patients. Two patients reported grade 3 dermatitis and 1 of those discontinued treatment as a result. Patients experiencing grade 3-4 AEs on the combination therapy numbered 17 or 55%. The most common grade 3-4 AEs were blood and lymphatic system disorders (9), anemia (4), and neutropenia (3).

Median 1-year survival was 61% (95% CI, 37-78). Clinical benefit was reported in 20 (71%) of patients, with 7 partial responses and 13 patients with stable disease. Median progression-free survival (PFS) was 8.9 months (95% CI, 4.3-not reached), which investigators said compared favorably with results of prior studies in similar patient populations. In a meta-analysis of phase III trials that involved 1640 patients with recurrent ovarian cancer after primary taxane/platinum therapy, investigators found that the median PFS of patients at their fourth relapse was 4.4 months and median overall survival was 6.2 months.

“The results of these previous studies, though not directly comparable to the phase II, single arm INNOVATE trial, strengthen the rationale for further evaluating the role of TTFields in the management of platinum resistant ovarian cancer,” investigators wrote.

Ovarian cancer, the second most common gynecologic malignancy, has a poor prognosis. Although most patients achieve a complete remission, 80% to 85% of patients will experience recurrence. Most will develop resistance to platinum therapy.

“A clear unmet need remains for patients with recurrent ovarian cancer, particularly for those patients resistant to platinum-based chemotherapy, with median overall survival of about 13 months post recurrence,” said lead author Ignace Vergote, chair of the Department of Obstetrics and Gynecology and Gynecologic Oncology at the Catholic University of Leuven, Belgium.

 “These phase II pilot data show that tumor treating fields combined with paclitaxel has the potential to increase survival without significantly increasing side effects for recurrent ovarian cancer patients.”

TTF has been tested in a variety of tumor types. The National Comprehensive Cancer Network (NCCN) became the first guideline-setting body to endorse the routine frontline use of TTF when it updated its glioblastoma treatment guidelines in March. That followed a 2011 FDA approval of the Optune TTF system for patients with glioblastoma following tumor recurrence. The system now carries an NCCN category 1 recommendation in combination with radiotherapy and temozolomide for patients with glioblastoma who have undergone surgery.

TTF is self-administered and non-invasive. Transducer arrays are connected to a small, portable medical device, then affixed to the abdomen. In the INNOVATE trial, patients were instructed to wear the device 18 hours per day for continuous delivery throughout the treatment period. Investigators noted median compliance at 3 months of 77% (14 h/day on average).

Patients with recurrent ovarian cancer who progress on paclitaxel following platinum-resistant disease are often treated with PLD, which has response rates below 20%. Gemcitabine and topotecan, 2 alternative treatments, have similarly low response rates, and there is limited data on the efficacy of additional treatments.

The design for INNOVATE-3, NovoCure’s phase III trial of its TTF technology in recurrent ovarian cancer, was disclosed in June at the American Society of Clinical Oncology (ASCO) Annual Meeting 2018.

Vergote I, von Moos R, Manso L, Van Nieuwenhuysen E, Concin N, Sesse C. Tumor treating fields in combination with paclitaxel in recurrent ovarian carcinoma: results of the INNOVATE pilot study [published online July 31, 2018]. 

Novocure to Present INNOVATE-3 Phase 3 Pivotal Trial Design in Recurrent Ovarian Cancer at the American Society of Clinical Oncology Annual Meeting 2018 [press release]. St. Helier, Jersey: NovoCure; June 4, 2018. novocure.com/novocure-to-present-innovate-3-phase-3-pivotal-trial-design-in-recurrent-ovarian-cancer-at-the-american-society-of-clinical-oncology-annual-meeting-2018/. Accessed August 1, 2018.

Gynecologic Oncology Publishes Results of the INNOVATE Phase 2 Pilot Study Demonstrating Combination of Tumor Treating Fields With Paclitaxel May Improve Survival Of Patients With Recurrent Ovarian Cancer [press release]. St. Helier, Jersey: NovoCure; July 31, 2018. novocure.com/gynecologic-oncology-publishes-results-of-the-innovate-phase-2-pilot-study-demonstrating-combination-of-tumor-treating-fields-with-paclitaxel-may-improve-survival-of-patients-with-recurrent-ovarian-ca/. Accessed August 1, 2018.

A version of this article was originally published by 

Tumor Treating Fields Show Promise in Ovarian Cancer

The addition of tumor treating fields (TTF), an antimitotic therapy that delivers continuous low-intensity electrical fields to the tumor region, to weekly paclitaxel (Taxol) appeared safe in the treatment of patients with platinum-resistant ovarian cancer.

Tumor Treating Fields May Address Unmet Need in Ovarian Cancer Treatment

As abemaciclib (Verzenio) has emerged as a promising agent for patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, the oncology nurse is now a key factor for these patients, according to Paula Fulgham, RN, OCN.

“If they leave with (an oral) medication, they don’t know how to take the drug, the side effects and what to expect, and they’re going to be at home (without medical advisement. It’s not like they are coming in every 3 weeks for chemo and we can coach them and guide them as they go along,” said Fulgham, who is chief nursing officer at the Cancer Center of Kansas in Wichita.

“These patients are now going to be in the driver’s seat,” she added. “Understanding how these drugs work and the side effects profile, and what to educate the patients with early on is so important.”

Annual School of Nursing Oncology, held Aug. 3-4 in Chicago, Fulgham offered an overview of abemaciclib regimens, and their associated adverse events (AEs) to review practical considerations for nurses to use.

In the randomized, double-blind phase III MONARCH 2 trial, women who recurred or progressed on or after endocrine therapy received abemaciclib plus fulvestrant (Faslodex). Overall, 86% of patients experienced diarrhea with a median onset occurring 6 days after treatment started.

With this, Fulgham recommended for patients to have an over-the-counter antidiarrheal medication on hand before symptoms begin, and to know who and when to call when symptoms get out of control to ensure treatment continuation. She noted that it is up to the oncology nurse to understand the physiology of these patients and the AE profile of the drug to help determine whether a dose modification is necessary to resolve symptoms.

Additional AEs that occurred in the MONARCH 2 trial were nausea (45%), abdominal pain (35%), vomiting (26%), and stomatitis (15%). Additionally, fatigue (46%), peripheral edema (12%), and pyrexia (11%) of all grades were experienced. 

Nine percent of patients had to discontinue treatment due to an AE compared with 3% of patients who were treated with fulvestrant alone. Of these, 43% of patients required a dose reduction due to an AE. 

All-grade neutropenia occurred in 46% of patients, with death occurring in < 1% of patients due to neutropenia sepsis. Febrile neutropenia occurred in < 1% of patients. Fulgham noted that for patients who develop grade 3/4 AEs, dosage may be reduced, interrupted, or delayed.

Fulgham recommended for oncology nurses to provide patients with appropriate instructions that can be easily referenced at home. A sheet that goes through the basics, such as avoiding foods that interfere with the CYP3 pathway, would be more helpful to patients than a lengthy package insert.

Lastly, she stressed the importance of establishing an action plan that includes specific dosage times with patients before they start taking abemaciclib.

“Looking at the patient overall you want to know where their baseline is and how to monitor these patients as they go through the treatment,” Fulgham said. “We’ve had a great increase in our phone calls because nurses now see patients who are not coming in for chemotherapy regularly. Usually patients would discuss side effects at their follow-up appointments. These patients start these oral oncolytic they do have questions and monitoring. It’s important for nurses to understand when they discuss with the patients.”

Fulgham P. A CDK4&6 inhibitor for women with HR+, HER2-, MBC: Including those with concerning clinical characteristics. Presented at: the 2nd

Annual School of Nursing Oncology; Aug. 3-4, 2018; Chicago.

Managing Adverse Events in Patients Taking Abemaciclib

The favored use of immune checkpoint inhibitors in oncology has led to an increase in immune-related adverse events (IRAEs), which if not managed properly, can be life-threatening. However, this can be addressed if nurses use the 5 pillars of managing IRAEs: prevent, anticipate, detect, treat, and monitor.

At the 2nd Annual School of Nursing Oncology™, held from Aug. 3-4 in Chicago, Marianne Davies DNP, RN, CNS, ACNP-BC, AOCNP, an assistant professor and oncology nurse practitioner at the Yale Comprehensive Cancer Center, presented an overview of IRAEs nurses should look out for, and how to respond to them when they are identified.

“This has been an incredibly active field over the past several years in terms of the approval of several immune checkpoint inhibitors,” said Davies. “What’s import to understand is that the approvals are slightly different across the disease entities. Some of the dosages require modification, [therefore] you really need to understand the dosing schedule and that it might be different for different lines of therapy. Some of these agents are approved in the first-, second- and third-line setting. It’s not just a one-size-fits-all administration.”

IRAEs can include dermatologic, gastrointestinal (GI), pulmonary, and endocrine toxicities, which are unique to immunotherapy agents since adverse events (AEs) in this organ system were not previously seen in targeted therapies or chemotherapy, Davies said.

Treatment of IRAEs depends on the organ system and severity of onset, but usually involves steroids and other immunosuppressant drugs for grade 1 toxicities, treatment dose delays for grade 2 toxicities, or discontinuation of the immunotherapy agent itself for grade 3-4 (Table 1).

Davies says the most common adverse events are dermatologic toxicities. Patients can present with maculopapular rash or an increased manifestation of their eczema or psoriasis.

Jane Arboleda, ARNP from the Miami Cancer Institute in Florida, who presented at the conference on pembrolizumab (Keytruda) and its role in the treatment of metastatic non-small cell lung cancer, said connecting the patient to a dermatologist who has knowledge of immunotherapy-related dermatologic toxicities before beginning therapy may be valuable for patients who are most susceptible to dermatologic AEs. She says trying to procure an initial appointment after symptoms begin could mean weeks of discomfort and dose delay as a result of long wait times. It is essential that the oncology nurse involve the oncologist and patients in treating symptoms to bridge the gap between onset of toxicity and treatment by the specialist.

“It’s important to collaborate with your dermatologist, whether it’s someone within your community or your institution. Where I’m from in Miami, it can take up to 6-8 weeks to see a dermatologist. If you have something very serious, or life-threatening, that’s something the patient cannot afford,” Arboleda stressed.

When discussing pulmonary toxicities, Arboleda further emphasized the potential for pembrolizumab to result in severe cases of pneumonitis. An analysis of 2790 patients selected across numerous KEYNOTE trials, 6.9% of patients taking the anti&shy;&shy;&shy;—PD-1 agent experienced pneumonitis as opposed to 2.9% in the control arms.

“It’s important to note that pneumonitis occurs frequently in patients with history of thoracic radiation,” said Arboleda.

Davies recommends ruling out other causes of pulmonary distress such as disease progression or infection. In all cases of pneumonitis, an infectious workup is recommended to determine if the cause is immune-related and warrants treatment discontinuation.

The onset of gastrointestinal IRAEs can occur anywhere from 3 days to 10 weeks after treatment initiation. Appropriate nursing counseling, including foods to avoid, is important for patients beginning immunotherapy. Colitis and diarrhea are more commonly seen in patients on anti-CTLA4 agents and combination therapies. Risks associated with GI toxicities are bowel perforation and sepsis.

“Patients might have altered bowel patterns if they’re on opioids for pain management [and] they may have significant constipation. If their bowel pattern was such that they were going every two to three days, or maybe even longer, and now they’re going twice per day, that may be a significant toxicity,” said Davies. A baseline assessment is crucial in assessing future bowel dysfunction.

Management of endocrine toxicities is a new consideration for oncology nurses who may not be accustomed to managing AEs related to this organ system with chemotherapy or targeted therapies, Davies noted. Unlike other IRAEs, most events up to grade 4 can be managed with endocrine therapy to avoid dose delay or discontinuation.

Treatment with steroids and immunosuppressant drugs should be managed to mitigate the risk of refractory IRAEs and other medication side effects. Long-term exposure to steroids may require a proton pump inhibitor or beta blocker depending on pre-existing conditions and dose tapering over at least a 30-day period to prevent recurrence. Patients being treated for months at a time will be at risk for osteoporosis and should be treated with Vitamin D and calcium.

IRAEs can occur between 5-12 weeks after treatment has started; however, they can occur months, or even years, after treatment discontinuation. Davies noted that anti-CTLA-4 agents are the most likely to cause toxicities because they initiate activity “upstream” in the immune process. This risk is increased with combination therapies, especially with anti-PD-L1 and anti-PD-1 agents.

The role of the oncology nurse in managing IRAEs starts with a baseline assessment before immunotherapy treatment has started. Having an extensive understanding of the immune system and the likelihood of developing toxicities can be achieved by laboratory evaluations, medication reconciliation, and knowledge about preexisting autoimmune diseases, Davies explained. 

Current research focus is centered on predictive markers in patients that will anticipate IRAEs and their sequencing before immunotherapy is initiated. Davies recommends oncology nurses acquaint themselves with National Comprehensive Cancer Network (NCCN) 

The favored use of immune checkpoint inhibitors in oncology has led to an increase in immune-related adverse events (IRAEs), which if not managed properly, can be life-threatening. 

Audrey Sternberg