Results from a prespecified analysis of the phase 3 CLEAR trial (NCT02811861) found that lenvatinib (Lenvima) plus pembrolizumab (Keytruda) improved progression on next line of therapy (PFS2) outcomes compared with sunitinib (Sutent) in patients with advanced renal cell carcinoma (RCC), according to findings presented at the 

The median PFS2 was not reached (95% CI, not estimable [NE]-NE) for the 355 patients in the lenvatinib plus pembrolizumab cohort compared with 28.7 months (95% CI, 23.0-NE) among the 357 patients in the sunitinib cohort. The risk of second progression was reduced by 50% (HR, 0.50; 95% CI, 0.39-0.65).

At the 24-month mark, PFS2 rate was 72.7% (95% CI, 67.3%-77.4%) and 54.2% (95% CI, 48.4%-59.6%) in the investigative combination therapy and sunitinib arms, respectively. At 36 months, PFS2 rate was 61.9% (95% CI, 53.7%-69.0%) and 42.9% (95% CI, 32.8%-52.5%) in the lenvatinib/pembrolizumab arm and sunitinib arm, respectively.

“These findings remained consistent after accounting for subsequent therapies, as evidenced by PFS2 and adjusted overall survival,” the authors wrote in a poster of the data. “These results further support the use of lenvatinib plus pembrolizumab as a standard-of-care first-line treatments for patients with [advanced] RCC.”

A total of 117 patients in the lenvatinib plus pembrolizumab cohort and 206 patients in the sunitinib cohort went on to receive another therapy. Median time to next-line therapy was 12.2 months (range, 1.45-37.36) and 6.4 months (range, 0.39-28.52) in the lenvatinib/pembrolizumab and sunitinib groups, respectively.

The most common next-line of therapy was anti-VEGF treatment, mainly cabozantinib (Cabometyx) which was received by 33.0% of patients in the lenvatinib/pembrolizumab cohort and 57.7% in the sunitinib group. Other therapies included checkpoint inhibition (30.4% and 33.6%, respectively), MTOR inhibition (8.2% and 43.1%), CTLA-4 inhibition (1.7% and 5%), and other (1.7% and 5%).

A PFS2 benefit was also seen with lenvatinib plus pembrolizumab over sunitinib in patients with favorable-risk disease (HR, 0.47; 95% CI, 0.26-0.87), intermediate-risk disease (HR, 0.53; 95% CI, 0.39-0.71), and poor-risk disease (HR, 0.42; 95% CI, 0.20-0.88) defined by Memorial Sloan Cancer Center risk criteria.

Similarly, when defined by International Metastatic Renal Cell Carcinoma Database Conortium risk groups, median PFS2 was not reached for the favorable, intermediate, or poor-risk groups for those on lenvatinib plus pembrolizumab, and was 34.7 months (95% CI, 28.7-NE), 23.0 months (95% CI, 17.7-NE), and 10.2 months (95% CI, 4.2-12.2), in the sunitinib groups, respectively.

Median duration of first subsequent treatment was 5.2 months (range, 0.10-31.23) for the lenvatinib plus pembrolizumab cohort and 6.8 months (range, 0.03-30.72) in the sunitinib cohort.

To be eligible for the trial, patients had to have a histologically or cytologically confirmed diagnosis of RCC with clear-cell components and documented evidence of advanced disease. Patients could not have undergone prior systemic therapy have one or more measurable lesion per RECIST 1.1 criteria and a Karnofsky performance score of 70 or higher.

Voss MH, Powels T, McGregor BA, et al. Impact of subsequent therapies in patients (pts) with advanced renal cell carcinoma (aRCC) receiving lenvatinib plus pembrolizumab (LEN + PEMBRO) or sunitinib (SUN) in the CLEAR study. 

. 2022;40(suppl 16):4514. doi:10.1200/JCO.2022.40.16_suppl.4514

Articles

Frontline treatment with lenvatinib plus pembrolizumab decreased risk of disease progression or death by 50% compared with sunitinib in advanced renal cell carcinoma.

Lenvatinib/Pembrolizumab Boosts Outcomes For Next Line Therapy in Advanced Renal Cell Carcinoma

Despite the majority of patients in a recent study stating that their oncologist told them that their multiple myeloma was incurable, a substantial amount believed that they could still be cured. Further, prognostic awareness was associated with higher rates of psychosocial distress and symptom burden and lower quality of life (QOL) in patients with myeloma.

These findings were recently presented at the 2021 ASH Annual Meeting and Exposition.

“Multiple myeloma is an incurable hematologic malignancy requiring long-term continuous therapy. Despite its chronic and unrelenting course, studies examining quality of life, psychosocial distress and prognostic awareness by line of therapy are lacking,” study author Betsy O’Donnell, MD, director of Lifestyle Medicine and medical oncologist in the Multiple Myeloma Disease Center at Massachusetts General Hospital said while presenting the findings.

In an attempt to fill this research need, O’Donnell and her team conducted a cross-sectional, multi-site study of 180 patients with multiple myeloma. Sixty patients were newly diagnosed, 60 underwent 2-3 lines of therapy, and 60 underwent 4 or more lines of therapy. Individuals on maintenance therapy were excluded. A validated questionnaire was used to analyze patient’s feelings of QOL, symptom burden, fatigue, psychological distress, and perceptions of prognosis.

The average age of study participants was 68, 52% were female, and 89% were white.

Findings revealed that there was no significant difference in QOL, symptom burden, fatigue, depression, anxiety, or PTSD symptoms by line of therapy. Overall, 24% of patients were experiencing clinical depression, 24% anxiety and 24% PTSD.

The majority (84%) of patients reported that it was “extremely” or “very” important to know about their prognosis, with 66% stating that they received adequate information on their prognosis.

“Patients reported that prognostic information was extremely or very helpful in making decisions about treatment, coping with disease and preparing for the future,” O’Donnell explained.

Interestingly, 85% of patients reported that their oncologist told them that their cancer was curable, but only 31% acknowledged that they were terminally ill, and 42% reported that they believed their cancer was curable.

Patients who were receiving 2-3 lines of therapy were more likely than those getting their first line of therapy to acknowledge their terminal illness (36.7% versus 19.6%; 

=0.045) and that their disease was not curable (90% versus 75.9%; 

“With regard of treatment goals, nearly 23% of all patients report that their primary goal of therapy was cure, and 18% reported that their oncologists’ primary goal was cure,” O’Donnell said. “Although the majority reported that their oncologist had told them their cancer was incurable, a substantial proportion still report that they believe that they were curable.”

The patients who acknowledged their terminal illness reported higher rates of depression, anxiety, and symptom burden, as well as lower QOL.

O’Donnell concluded, “Multiple myeloma patients undergoing treatment experience impaired quality of life and elevated psychological distress across the disease and continued irrespective of their line of therapy … Interventions are needed to improve patient QOL, reduce their psychological distress and cultivate adaptive coping strategies that may help improve the patient experience over the multiple myeloma disease course.”

O’Donnell E, Shapiro Y, Nadeem O, et al. Quality of life, psylogical distress, and prognostic awareness in patients with multiple myeloma. Presented at: Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 4082

Patients with myeloma who reported that their disease was incurable had lower quality of life. However, many patients may also have misconceptions about the curability of their disease. 

Prognostic Awareness Impacts QOL in Patients With Myeloma 

When patients with cancer experience depression and anxiety, they are less likely to enroll in oncology clinical trials, according to findings presented at the 2021 American Society of Hematology Annual Meeting and Exposition.

“Although thousands of cancer clinical trials are available today, engagement remains low, with only 2% to 7% of cancer patients in the United States participating in cancer clinical trials,” study author Victoria Morris, PhD, research director at the Cancer Support Community, said while presenting the findings. “There are many systemic and person-level factors that can contribute to this lack of engagement…However, another contributing factor that can impact participation is attitudinal barriers such as fear-based perceptions about what it means to participate in a cancer clinical trial.”

The observational, cross-sectional study involved 625 patients with blood cancer (46.4% myeloma; 19.5% chronic lymphocytic leukemia; 11.4% non-Hodgkin lymphoma; 4.0% acute myeloid leukemia; 3.5% Hodgkin lymphoma; 3.2% chronic myeloid leukemia; 1.6% acute myeloid leukemia; 1.3% myeloproliferative neoplasm; 7.4% other lymphoma; and 1.8% other leukemia).

Participants filled out Cancer Support Community’s Cancer Experience Registry, which includes sociodemographic and clinical data as well as ranking on a scale of 0 (strongly disagree) to 4 (strongly agree) on 8 statements about clinical trials. Participants also completed the Anxiety and Depression subscales from the Patient-Reported Outcomes Measurement Information System (PROMIS-29v2.0).

PROMIS responses were averaged to determine the level of depression and anxiety on a 5-point scale, while 8 hierarchical regression models were examined—one for each of the clinical trial perception variables—to determine the impact that depression and anxiety had on how patients think of clinical trials. Clinical history and sociodemographic variables were controlled for.

“Regression models indicated that psychosocial distress comprised of both depression and anxiety accounted for a significant amount of variance in 7 of the 8 clinical trial perceptions, above and beyond the controls,” Morris said. “Depression and anxiety—2 psychosocial factors that are highly prevalent in the cancer space—can bias attention in was that alter perceptions, thus potentially playing a role in trial perceptions.”

The average anxiety and depression score was 1.91 (SD = .93). These psychosocial effects were predictors for the following perceptions:

“I would be unable to fulfill trial requirements due to logistical barriers.” (15% of participants responded “agree” or “strongly agree”; 

“I don’t trust the medical establishment and fear I will be used as a ‘Guinea pig.’” (13%; 

“I am uncomfortable being randomly assigned.” (53%; 

“I fear receiving a placebo (for example, a sugar pill) in a clinical trial.” (49%; 

“I don’t understand what clinical trials are.” (8%; 

“There are no clinical trials available in my community.” (30%; 

“I fear side effects that might come with treatment on a clinical trial.” (46%; 

The only perception that anxiety and depression did not impact, however, was the belief that insurance would not cover the clinical trial.

These findings show that clinicians should consider psychosocial barriers when discussing the options of clinical trial participation to patients.

“While attempts to alter perceived barriers to participation in cancer clinical trials often focus on information dissemination to address misconceptions about cancer clinical trials, the present study indicates that underlying person-level psychological factors may shape perceptions about cancer clinical trials and need to be considered,” Morris said.

This study should just be the first of more research that should analyze the magnitude and directionality of these findings, according to Morris.

“But one thing is clear: the decision about whether to engage in a cancer clinical trial is complex and multi-faceted, and any and all barriers to participation need to be considered so that we can better empower patients in their treatment decision making.”

Rogers K, Morris V, Miller M, LeBlanc T. The relationship between depression, anxiety, and clinical trial perceptions among patients with hematologic cancer. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 1901.

If patients with cancer experience depression or anxiety, it can result in low clinical trial enrollment. 


Patient Mental Health Key Factor in Cancer Clinical Trial Perception

Treatment with ≥ 2L cabozantinib (Cabometyx), compared with ≥ 2L axitinib (Inlyta) improved survival outcomes in patients with advanced renal cell carcinoma (RCC) who received prior VEGF-targeted therapy, according to a retrospective cohort study of data from Public Health England’s Cancer Analysis System (CAS), presented at the 2021 ESMO Congress.

The study analyzed outcomes of adults who were diagnosed with stage III or IV RCC between January 1, 2011 and December 31, 2018, with follow-up lasting until January 31, 2020. A total of 440 patients received cabozantinib treatment, while 1045 received axitinib.

Median duration of treatment was longer for those who received cabozantinib (5.52 months; IQR, 2.73-11.74) than those on axitinib (4.60 months; IQR, 1.45-12.36).

Patients on cabozantinib – a TKI inhibitor – also had numerically longer median overall survival (OS) than patients given axitinib. In the unweighted analysis, median OS for cabozantinib was 11.41 months (IQR, 5.65-27.32) compared with 9.60 months (4.54-20.32). Similar results were found in the IPW analysis, with average OS lengths of 11.24 months (IQR, 5.65-27.98) and 10.39 months (IQR, 4.70-20.03) for the cabozantinib and axitinib arms, respectively.

“Both agents have been approved in the U.K. as second or later line treatment options for patients with advanced RCC – axitinib since 2012, and cabozantinib since 2016,” said study author Janet Brown, MB BS, MSc, MD, FRCP, Professor of Translational Medical Oncology at University of Sheffield, in her presentation of the data.

Notably, patients in the cabozantinib arm tended to have a more recent diagnosis, with 65% receiving a diagnosis between 2016 and 2018. Conversely, 80% of those on axitinib were diagnosed before 2016. In the United States, cabozantinib was approved by the FDA in December 2017 for first-line treatment, based on findings from the CABOSUN (NCT01835158) trial, which showed improved progression-free survival over sunitinib (Sutent), at 8.6 months and 5.3 months, respectively.

Characteristics between the cabozantinib and axitinib patient groups were otherwise balanced, with the average age being 62.5 years and 63.0 years, respectively. At diagnosis, 58.6% of patients in the cabozantinib cohort and 53.2% of those on the axitinib cohort had metastases, while 91.4% and 90.3%, respectively, had clear-cell histology. Regarding tumor size at diagnosis, 69.3% and 68.8% were 4.00 mm or smaller, in the cabozantinib and axitinib arms, respectively; 5.9% and 7.1% had tumors larger than 4.00 mm, and the remainder (24.8% and 24.1%) of patients had missing tumor sizes.

At diagnosis, 28.2% of patients given cabozantinib had an ECOG score of 0-1, compared with 20.4% of those on axitinib.

“Real-world evidence complements the results of randomized controlled trials,” Brown said. “This study demonstrates the potential for cabozantinib for conducting clinically relevant real-world research in England.”

Brown J, Harrow B, Marciniak A, McCarthy C, Cirneanu L, Protheroe A. Cabozantinib and axitinib after vascular endothelial growth factor therapy in patients with advanced renal cell carcinoma: a retrospective cohort study. Presented at: ESMO Congress 2021. September 16-21, 2021. Virtual. E-Poster 680P

Patients with advanced RCC who received prior VEGF-targeted therapy tend to have longer survival outcomes with cabozantinib than with axitinib.

UK Study of Real-World Data Shows Survival Benefit of Cabozantinib vs Axitinib in Pre-Treated RCC 

For this episode of “The Vitals,” we spoke with Chastity Washington, MPH, CHES, Center for Cancer Health Equity, Ohio State University, about how the COVID-19 pandemic has exacerbated preexisting disparities in cancer care. Chastity spoke to our team about the direct and indirect impacts of COVID 19 on disadvantaged communities, vaccine hesitancy amongst those communities, and more.

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“We’ve had periods of time where things were shut down. We do have telemedicine, that was expanded, but telemedicine doesn’t work for everyone. If you don’t have internet access, if you don’t have the ability to understand the technology….”


COVID-19 Pandemic Emphasizes Disparities in Cancer Care

Although chimeric antigen receptor (CAR) T-cell therapies like ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) can lead to neurologic adverse events (AEs) in patients with relapsed/refractory multiple myeloma, the toxicities can be managed without long-term effects as long as they are treated promptly, according to findings from CARTITUDE-2 presented at the European Hematology Association 2021 Virtual Congress.

“To date, more than 100 patients across the CARTITUDE study program have been dosed with cilta-cel. When implemented, patient [treatment] strategies have reduced the incidence of neurotoxicity, including movement and neurocognitive events,” said Hermann Einsele, MD, FRCP, professor and chair of the Department of Internal Medicine at the Julius Maximilians University of Würzburg in Germany, during a presentation of the study findings.

The open-label, phase 2, multicohort CARTITUDE-2 (NCT04133636) trial evaluated the efficacy and safety of cilta-cel in patients with multiple myeloma. For the purpose of studying adverse vents (AEs), the investigators analyzed cohort A, which involved patients with multiple myeloma who progressed after 1 to 3 lines of therapy, including a proteasome inhibitor or an immunomodulatory drug.

Eligible patients were adults with measurable disease and ECOG performance status of 0 or 1. Their disease had to be refractory to lenalidomide (Revlimid) and not previously treated with another BCMA-targeted drug.

Patients received cilta-cel (0.75 × 106 [range: 0.5-1.0 × 106] CAR+ viable T cells/kg) as a single infusion 5 to 7 days after the initiation of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days).

“Patient [treatment] strategies included more effective bridging therapy to reduce baseline tumor burden, early aggressive treatment of [cytokine release syndrome] and [immune effector cell-associated neurotoxicity], as well as handwriting assessment for early detection of symptoms of neurotoxicity,” Einsele said. “These strategies have been successfully implemented across the CARTITUDE program.”

At a median follow-up of 5.8 months (range, 2.5-9.8), 20 patients in cohort A received cilta-cel, of which 4 (20%) experienced at least 1 neurotoxicity. Three patients had grade 1/2 immune effector cell-associated neurotoxicity (ICANS) along with cytokine release syndrome. The median time to symptom onset was 8 days (range, 7-11), and, on average, symptoms lasted 2 days. Two patients received supportive measure for their ICANS, including levetiracetam and steroids.

One patient experienced isolated grade 2 facial paralysis on day 29. The patient recovered 51 days later after being treated with dexamethasone for 28 days. Overall, there were no movement or neurocognitive disorders reported within cohort A.

“Importantly, none of the patients in the cohort A of the CARTITUDE study experienced other neurotoxicities that were seen in CARTITUDE-1 (NCT03548207),” Einsele said.

Einsele H, Parekh S, Madduri D, et al. Incidence, mitigation, and management of neurologic adverse events in the phase 2 CARTITUDE-2 study of ciltacabtagene autoleucel in patients with multiple myeloma. Presented at: 2021 European Hematology Association Congress. June 9-17, 2021; virtual. Abstract EP1003.

In the cohort of patients with multiple myeloma, there were no grade 3 or higher neurotoxicities. 


Neurotoxicity With Cilta-cel: Early Intervention Can Improve Outcomes in R/R Myeloma

Oral cancer therapies can be appealing to patients, particularly during the COVID-19 era, because they can be taken at home. However, at-home medication can also pose a threat to adherence. Oncology nurses therefore need to remain diligent in educating their patients and monitoring their adherence.

“You avoid intravenous infusions; I’m all about that. And patients feel empowered [taking their medication at home], but we have to give them the tools to succeed,” said Patricia Jakel, MN, RN, AOCN, a clinical nurse specialist in the Solid Tumor Program at UCLA Medical Center, at the 5th Annual School of Oncology Nursing Annual Meeting.

Patients may be burdened with complicated medication schedules, that could include taking 1 drug to ensure that another works properly, as well as adverse event management. Add chemotherapy-related cognitive impairments – commonly referred to as “chemo brain” – and clinicians may be surprised to see how many patients are struggling with their medications. Jakel admitted she has struggled with chemo brain.

“I’m a breast cancer patient [who was] on treatment for the last 4 years. Oral adherence was not the best for me, so I have personal experience with it,” Jakel said. She joked, “I used to be smart. I used to be really smart, and chemo brain has really affected me. It doesn’t matter if you’re taking oral agents, IV agents, or anti-estrogen agents. [Chemo brain] is really real to patients.”

Cancer treatments can affect memory, executive functioning, and a patient’s ability to organize their thoughts. Their ability to pay attention or processing speed may be affected, too. Jakel said that cognitive training, which could be as simple as doing puzzles or keeping up to date on the latest news in an area of interest, can help curb the effects of chemo brain, as can complementary treatment methods such as acupuncture.

“Poor adherence decreases clinical benefits and overall effectiveness of the healthcare system,” she said. “It not only affects the patient, but these patients who are non-adherence actually end up back in the hospital and end up with other complications.”

Strikingly, 20%-30% of medication prescriptions are never filled. And according to Jakel, there are factors besides chemo brain that contribute to non-adherence.

In her experience, Jakel has seen patients stop taking their medications once they start to feel better or that the drug is working. Others may be experiencing cost barriers or psychosocial issues that prevent them from taking their medication as prescribed. “Make sure you talk to your patients about … the reasons why they’re not taking [their medication.]”

There are steps that clinicians can take to help their patients improve medication adherence. Some are simple, like calling and checking in on them, asking them to keep a drug diary, or conducting pill counts. Doctors can also encourage patients to use apps or alarms on their phone that reminds them to take their drugs.

When discussing medication adherence, clinicians should be careful of their word choice, Jakel said.

“What I say [to patients] is ‘Tell me how you’re taking your medication.’ I don’t say ‘Are you taking it?’” Jakel said. “I think that’s very important to have them talk to you.”

Additionally, caregivers should be educated on proper drug handling, scheduling, and potential drug-drug interactions.

“Make sure that education is done for the family and the caregiver,” Jakel said. “Hopefully the patient has a caregiver or a friend or family member helping them, because that’s critical for adherence.”

Ultimately, when patients do not take their cancer drugs properly, it can lead to a barrage of other complications that will have negative consequences both for the individual with cancer and the healthcare system.

Jakel P. Breast Cancer Supportive Care in 2021. Presented at: 5th Annual School of Nursing Oncology. August 6-7, 2021. Virtual.

With a newfound abundance of available oral cancer therapies, it has become necessary for oncology nurses to ensure that their patients are adhering to treatment. 



Oncology Nurses Must Stress Importance of Medication Adherence 

Data from CARTITUDE-2 suggests that patients with relapsed/refractory multiple myeloma who experience adverse events (AEs) as a result of CAR T-cell therapies such as ciltacabtagene autoleucel (Cilta-cel or JNJ-68284528) can manage those symptoms without long-term lasting effects, so long as they are caught and treated promptly.

“To date, more than 100 patients across the CARTITUDE study program have been dosed with cilta-cel. So when implemented, patient management strategies have reduced the incidence of neurotoxicity, including movement and neurocognitive events,” said Hermann Einsele, MD, FRCP, professor of internal medicine at the Julius Maximillians University of Würzburg in Germany, while presenting the study findings.

The open-label, phase 2, multicohort CARTITUDE-2 (NCT04133636) trial evaluated the efficacy and safety of cilta-cel in patients with myeloma. For the purpose of studying AEs, the researchers analyzed cohort A, which involved patients with myeloma that progressed after 1-3 lines of therapy, including a proteasome inhibitor and an immunomodulary drug.

Eligible patients were adults with measurable disease and ECOG performance status of 0 or 1. Their disease was refractory to lenalidomide (Revlimid) and was not previously treated with another BCMA-targeted drug.

Patients received cilta-cel (0.75×10 6 [range: 0.5–1.0×10 6] CAR+ viable T cells/kg) as a single infusion 5–7 days after the initiation of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days).

“Patient management strategies included more effective bridging therapy to reduce baseline tumor burden, early aggressive treatment of [cytokine release syndrome] and [immune effector cell-associated neurotoxicity], as well as handwriting assessment for early detection of symptoms of neurotoxicity,” Einsele said. “These strategies have been successfully implemented across the CARTITUDE proves.”

At a median follow-up of 5.8 months (range, 2.5-9.8 months), 20 patients in cohort A received cilta-cell, and 4 (20%) experienced at least 1 neurotoxicity. Three patients had grade 1/2 immune effector cell-associated neurotoxicity (ICANS) alongside cytokine release syndrome. The median time to symptom onset was 8 days (range, 7-11), and, on average, symptoms lasted 2 days. Two patients received supportive measure for their ICANS, including levetiracetam and steroids.

There was 1 patient who experienced isolated grade 2 facial paralysis on day 29. The patient recovered 51 days later after being treated with dexamethasone for 28 days. Overall, there were no movement or neurocognitive disorders that were reported within Cohort A of the study.

“Importantly, none of the patients in the cohort A of the CARTITUDE study experienced other neurotoxicities that were seen in CARTITUDE-1,” Einsele said.

Einsele H, Parekh S, Madduri D, et al. Incidence, mitigation, and management of neurologic adverse events in the phase 2 CARTITUDE-2 study of ciltacabtagene autoleucel in patients with multiple myeloma. Presented at: 2021 European Hematology Association Congress. June 9-17, 2021. Virtual. Abstract EP1003.

This article was originally published on OncLive as 

“Early Intervention For Neurotoxicity Can Improve Outcomes With Cilta-Cel in Relapsed/Refractory Multiple Myeloma”

Data presented at the European Hematology Association 2021 Virtual Meeting revealed that CAR T-cell therapy-related adverse effects can be managed.

Prompt Treatment of CAR T-Cell Therapy-Related AEs Can Prevent Long-Term Lasting Effects 

Updated data from the phase 3 CheckMate-648 trial (NCT03143153) revealed that the addition of nivolumab (Opdivo) to either ipilimumab (Yervoy) or chemotherapy was associated with improved survival outcomes in the frontline treatment of patients with unreselectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) in comparison to chemotherapy alone, according to a presscast presentation ahead of the 2021 ASCO Annual Meeting.

“Advanced esophageal squamous cell carcinoma carries a poor prognosis, with a median survival of around 10 months,” said Ian Chau, MD, FRCP, consultant medical oncologist at the Royal Mardsen Hospital in the United Kingdom, while presenting the findings during the presscast.

CheckMate-648 is a randomized phase III trial that was presented at a presscast ahead of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting evaluating the efficacy of the following treatment regimens in adult patients with histologically confirmed squamous cell carcinoma or adenosquamous cell carcinoma of the esophagus that is deemed inoperable and cannot be treated with chemoradiation with curative intent:

: nivolumab 240 mg on day 1 and day 15; fluorouracil 800 mg/m2 per day on day 1 through day 5, for 5 days; and cisplatin 80 mg/m2 on day 1 of the 4-week cycle (n = 321).

: nivolumab 3 mg/kg every 2 weeks, followed by ipilimumab 1mg/kg every 6 weeks until unacceptable toxicity or disease progression (n = 325).

Eligible patients had an ECOG PS score of 0 to 1, measurable disease, and no prior systemic treatment for advanced disease. The primary end points in the trial were overall survival (OS) and progression-free survival (PFS) in patients whose tumors had PD-L1 expression ≥ 1%. Secondary end points were OS and PFS in all patients, as well as objective response rate (ORR), both in patients with PD-L1 ≥ 1% and all patients.

At a minimum follow-up of 12.9 months, median OS in patients with PD-L1 ≥ 1% in the nivolumab plus chemotherapy arm (n = 158) was 15.4 months (95% CI, 11.9-19.5), and was 13.7 months (95% CI, 11.2-17.0) in the nivolumab plus ipilimumab arm (n = 158). In the PD-L1-positive patients in the chemotherapy alone arm (n = 157) median OS was 9.1 months (95% CI, 7.7-10.0; 

“This translates into over 6 months [of] improvement in median overall survival [when comparing nivolumab plus chemotherapy to chemotherapy alone],” Chau said. “But importantly, if you look at the latter parts of the overall survival curve, they’re widely separated in favor of nivolumab plus chemo, meaning that there were more patients with prolonged overall survival.”

In the overall study population–regardless of PD-L1 expression–the median OS in the nivolumab plus chemotherapy arm was 13.2 months (95% CI, 11.1-15.7); 12.8 months in the nivolumab plus ipilimumab arm (95% CI, 11.3-15.5 months); and 10.7 months in the chemotherapy arm (95% CI, 9.4-11.9; 

The primary end point of PFS per blind independent committee review (BICR) was not met in patients whose tumors were PD-L1 positive (HR, 1.02; 95% CI, 0.73-1.43).

The ORR in patients with PD-L1-positive tumors given nivolumab plus ipilimumab was 35% (95% CI, 28-43). In the chemotherapy arm it was 20% (95% CI, 14-27). In all patients, ORR was 28% (95% CI, 23-33) and 27% (95% CI, 22-32) in the nivolumab plus ipilimumab and nivolumab plus chemotherapy arms, respectively.

Regarding safety, the most common (occurring in 10% or more) treatment-related adverse events (TRAEs) for the chemotherapy-containing arms were nausea, decreased appetite, and stomatitis. For the nivolumab/ipilimumab arm, common TRAEs were rash, pruitis, and hypothyroidism. Notably, incidence of TRAEs was consistent with all treated patients across all arms for patients whose tumor cell had PD-L1 expression ≥ 1%.

Ultimately, nivolumab-containing regimens have the potential to drastically improve outcomes in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma–a group that tends to have poor prognoses.

“Nivolumab plus chemotherapy [and] nivolumab plus ipilimumab each represents a new potential first-line standard of care for patients with advanced esophageal squamous cell carcinoma, based on the results of CheckMate-648, the largest randomized control trial conducted in this setting to date,” Chau said.

Chau I. First results from the CheckMate 648 study evaluating nivolumab plus ipilimumab or nivolumab plus chemotherapy versus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma. Presented at: 2021 ASCO Annual Meeting Press Program, May 28, 2021.

A study to evaluate efficacy in subjects with esophageal cancer treated with nivolumab and ipilimumab or nivolumab combined with fluoraucil plus cisplatin versus fluorouracil plus cisplatin (CheckMate648). Clinicaltrials.gov. Updated May 7, 2021. Accessed June 1, 2021. 

https://clinicaltrials.gov/ct2/show/NCT03143153

This article was originally published on OncLive as “Frontline Nivolumab Plus Ipilimumab or Chemo Improves Survival Outcomes in Advanced ESCC"

Survival outcomes in the frontline treatment of patients with unresectable advanced or metastatic esophageal squamous cell carcinoma were improved when nivolumab was added alongside either ipilimumab or chemotherapy.

Patients With Advanced ESCC Experience Improved Survival Outcomes With Addition of Nivolumab to Ipilimumab or Chemotherapy 

As news headlines warn the public about potential myocarditis from the COVID-19 vaccine, patients with cancer may be even more apprehensive to get immunized. However, it’s not “a close call at all” when outweighing the risks versus benefits in this population, according to Brahm Segal, MD, who advocates for everyone eligible to be vaccinated.

“Serious toxicities in the general public are few… and so far, there’s no obvious safety concern with patients with cancer that would argue that the vaccine is less safe among them compared to the general public,” said Segal, chair of Internal Medicine and chief of Infectious Diseases at Roswell Park Comprehensive Cancer Center.

Segal mentioned that many cancer treatments – including checkpoint inhibitors, which are widely prescribed across many cancer types – also run the risk of patients developing cardiotoxicity. Additionally, if patients are not immunized against COVID-19 and contract the virus, the disease itself carries risks to the heart.

“The heart is one of the organs that can be affected in a big way,” Segal said.

Segal also stressed that it is important not only for patients with cancer to get the vaccine, but also their loved ones with whom they are in close contact.

“Family members and their household members and friends should all be immunized as well, because in patients with cancer, some of the cancers and some of the therapies for cancer can disable the vaccine from being fully effective,” Segal explained. “So even though they’ve been vaccinated, they may not get the same protection that people with a normal immune system have. The way to address that is for the patients to be immunized, but also – as much as possible – the people around them to be vaccinated, too.”

While most patients should get vaccinated, those who should delay their shots are “few and far between,” Segal said.

“People who are having a stem cell transplant don’t want to have a vaccine right before transplant, right during, or in the immediate [period after] transplant period, because it’s extremely unlikely that there’ll be a lasting response,” he said.

Segal explained that there are specific guidelines for when patients undergoing transplants should be vaccinated, “But for the vast majority of patients with cancer, there’s no reason to wait. They should get immunized,” he said.

Many patients with cancer may feel uneasy about the COVID-19 vaccines, especially as new stories break about potential heart complications. However, most patients should get the shot as soon as possible, says Brahm Segal, MD.

Brielle Benyon