Ariana Pelosci

Opdivo plus Cabometyx resulted in a benefit versus Sutent in the first-line of advanced renal cell carcinoma treatment. © stock.adobe.com

Among patients with previously untreated, advanced renal cell carcinoma (RCC), treatment with Opdivo (nivolumab) plus Cabometyx (cabozantinib) resulted in long-term efficacy and manageable safety versus treatment with the standard of care, Sutent (sunitinib), study results have shown.

Progression-free survival: How long a patient lives without their disease spreading or worsening.

Overall survival: The time a patient lives, regardless of disease status.

Duration of response: How long a patient responds to treatment.

Overall response rate: Patients who responded partially or completely to treatment.

Complete response: The disappearance of cancer.

International Metastatic RCC Database Consortium (IMDC) risk group: A classification system to predict the prognosis and drive treatment decisions for patients with metastatic renal cell carcinoma.

Palmar-plantar erythrodysesthesia: Hand-foot syndrome.

Final follow-up results from the phase 3 

 were presented at the 2025 ASCO Genitourinary Cancer Symposium.

At the median follow up of 67.6 months for the intention to treat population, the median progression-free survival (PFS) was 16.4 months for patients who received Opdivo/CabometyxCabometyx and 8.3 months for those who received Sutent; median overall survival (OS) was 46.5 months versus 35.5 months, respectively, and median duration of response (DOR) was 22 months versus 15.2 months.

The overall response rate (ORR) was 55.7% versus 27.4% for patients in the Opdivo versus Sutent arms, respectively. Of patients who received Opdivo/Cabometyx, 20.1% experienced a partial response (PR) with 60% or more tumor reduction, and 21.7% received a PR with less than 60% tumor reduction. In the Opdivo/Cabometyx arm versus the Sutent arm, complete responses were observed in 45 and 15 patients, PRs in 135 and 75, stable disease in 104 and 136, progressive disease in 21 and 47 and unknown in 18 and 55.

“Long term efficacy benefit was observed with [Opdivo plus Cabometyx] over [Sutent] in these final results from the CheckMate 9ER trial, with a median of 67.6 months follow-up,” presenting author Dr. Robert J. Motzer, section head of Kidney Cancer in Genitourinary Oncology Service and Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center, and coauthors, wrote in the presentation. “The results continue to support [Opdivo plus Cabometyx] as a standard of care for previously untreated advanced RCC.”

A total of 651 patients were enrolled in the trial and randomly assigned to receive 240 mg of intravenous Opdivo every two weeks plus 40 mg of oral Cabometyx daily (323 patients) or 50 mg of oral Sutent daily on four weeks on, two weeks off schedule (328 patients). Eligible patients had previously untreated advanced or metastatic RCC with a clear cell component who were in any International Metastatic RCC Database Consortium (IMDC) risk group.

Of patients in the IMDC favorable risk group, the median PFS in the Opdivo/Cabometyx group (74 patients) was 21.4 months versus 12.8 months in the Sutent group (72 patients); median OS was 53.7 months versus 58.9 months, respectively, and ORR was 66.2% versus 43.1%.

In the IMDC intermediate or poor risk group, the median PFS in the Opdivo/Cabometyx group (249 patients) was 15.4 months versus 7.1 months in the Sutent group (256 patients); median OS was 43.9 months versus 29.2 months, respectively, and ORR was 52.6% versus 23%.

Patients with liver metastases had a median PFS was 10.9 months in the Opdivo/Cabometyx group (73 patients) and 6.2 months in the Sutent group (56 patients); median OS was 37.6 months and 22.1 months, respectively; ORR was 52.1% and 21.4%.

Of patients with bone metastases, the median PFS was 13.8 months in the Opdivo/Cabometyx group (79 patients) and 5.3 months in the Sutent group (75 patients); median OS was 34.8 months and 20.7 months, respectively; ORR was 49.4% and 9.3%.

Those with lung metastases demonstrated a median PFS was 16.4 months in the Opdivo/Cabometyx group (241 patients) and 8.3 months in the Sutent group (251 patients); median OS was 47.5 months and 32.4 months, respectively; ORR was 57.3% and 27.9%.

Additionally, 93% of patients in the Opdivo/Cabometyx group and 95% in the Sutent group discontinued treatment; 43% and 55%, respectively, received subsequent systemic therapies; 26% and 31% received two or more subsequent systemic therapies; and the most common was any VEGFR inhibitor (79%) in the Opdivo/Cabometyx group and any PD-L1 inhibitor (81%) in the Sutent group.

The median duration of therapy was 21.8 months in the Opdivo/Cabometyx group and 8.9 months in the Sutent group; 62% and 55% of patients had at least one dose reduction; and the median time to first dose reduction was 4.1 months and two months.

Regarding safety, common treatment-related side effects of any grade occurred in 98% of patients in the Opdivo/Cabometyx group and 93% of the Sutent group, and grade 3 (severe)/4 (life-threatening) treatment-related side effects occurred in 68% and 55%, respectively. The most common treatment-related side effects of any grade were diarrhea (60% and 46%, respectively), palmar-plantar erythrodysesthesia (39% and 42%), hypertension (34% and 35%) and hypothyroidism (37% and 31%). Also, 22% of patients to receive Opdivo/Cabometyx were administered corticosteroids to manage immune-mediated side effects of any grade. Any grade treatment-related side effects led to discontinuation in 28% and 11%, respectively.

Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate 9ER trial.” By Dr. Robert J. Motzer et al., 

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Articles

The combination of nivolumab and cabozantinib demonstrated superior long-term efficacy and manageable safety compared to sunitinib in untreated advanced renal cell carcinoma (RCC). The CheckMate 9ER trial showed improved progression-free survival, overall survival, and response rates with nivolumab/cabozantinib. The study included 651 patients, with significant benefits observed across various risk groups and metastatic sites. Common side effects included diarrhea and hypertension, with a higher incidence of severe side effects in the nivolumab/cabozantinib group. These findings support nivolumab/cabozantinib as a standard treatment for advanced RCC.

Opdivo plus Cabometyx resulted in a significant progression and survival benefits compared with Sutent in the first-line treatment of patients with advanced renal cell carcinoma.

Opdivo Plus Cabometyx Safe, Effective in Advanced Renal Cell Carcinoma

Results were consistent with research in advanced renal cell carcinoma treated with Cabometyx, Opdivo and Yervoy: © SciePro - stock.adobe.com.

Patients with advanced renal cell carcinoma experienced a continued benefit in progression-free survival (PFS) after 45 months when treated with Cabometyx (cabozantinib) plus Opdivo (nivolumab) and Yervoy (ipilimumab), compared with patients receiving placebo plus Opdivo and Yervoy, according to updated trial findings.

These findings were shared as the final results of the phase 3 

Progression-free survival: the time a person lives with cancer without it getting worse

Intent-to-treat population: a group of patients who were randomly assigned to receive a particular treatment, whether or not they actually received that treatment or adhered to it

Overall survival: the time from diagnosis or treatment initiation when a patient with cancer is alive

Alanine aminotransferase increase: an elevation of an enzyme found in the liver, which may be an indicator of liver damage or disease

Aspartate aminotransferase increase: an elevation of a specific enzyme in tissues like the heart, liver, muscle, kidneys and brain that may indicate damage or disease in one or more of these organs

Palmar-plantar erythrodysesthesia syndrome: hand-foot syndrome, or a skin reaction that primarily affects the hands and soles of the feet

M2-like macrophages: a type of immune cell that plays a role in tissue repair and wound healing, in addition to immune system regulation

Visceral metastasis: cancer that spread from its original location to the internal organs like the chest, abdomen and pelvis.

The updated PFS in the intent-to-treat population was 16.6 months in the combination arm and 11.2 months in the placebo arm. The overall survival (OS) was 41.9 months in the Cabometyx arm and 42 months in the placebo arm.

The PFS for those in the intermediate risk group was 22.1 months in the Cabometyx arm and 11.3 months in the placebo arm; and for those in the poor risk group, results were 9.5 months versus 11.2, respectively. The OS in the intermediate group was 47.9 months in the Cabometyx arm versus 48 months in the placebo arm; and for the poor risk group it was 19.4 months versus 24 months between both arms, respectively.

“There were no significant differences in OS between the 2 arms in the [intent-to-treat] population or by… risk group,” Dr. Laurence Albiges, head of the Department of Oncology at Gustave Roussy in France, said during the presentation.

Overall, 428 patients were enrolled in the Cabometyx arm and 427 were enrolled in the placebo arm. The main area of interest was PFS, with a secondary focus on OS.

In the Cabometyx arm, 373 patients discontinued all study treatment versus 361 in the placebo arm, and reasons included progressive disease (40% versus 44%, respectively), side effect unrelated to disease progression (29% versus 21%) and side effect related to progression (5% versus 9%).

Treatment exposure and side effects did not differ much from previously reported analysis. However, Albiges noted the median average daily dose of Cabometyx was 22.4 mg versus 35.2 mg for placebo. Treatment-related side effects that led to discontinuation occurred in 49% versus 26%, respectively.

The most common treatment-related side effects of grade 3/4 (severe or life threatening) were alanine aminotransferase increase (26% versus 6%), aspartate aminotransferase increase (19% versus 5%), diarrhea (5% versus 3%) and palmar-plantar erythrodysesthesia syndrome (4% versus 0%).

RNA sequencing from tumor samples occurred in 398 patients. Overall, no clear molecular clusters were observed in relation to clinical outcomes, but the sample size for each was small.

When assessing different immune types, the M2-like macrophages were the best predictor of OS. These contribute to tumor growth, invasion and metastases because they suppress the immune response, and are associated with poor prognosis throughout different cancers. If patients have poor risk or present with visceral metastasis, they exhibited higher levels of M2-like macrophages.

It was found that the Cabometyx combination overcame the M2-like macrophage-mediated tumor response. For M2-like low, the median PFS was 22.1 months in the Cabometyx arm versus 16.7 months in the placebo arm. M2-like high had a median PFS of 10.1 months in the combination arm versus 5.95 months in the placebo arm. Additionally, the median OS for M2-like low was 47.8 months in the Cabometyx arm versus NE in the placebo arm. For M2-like high, the median OS was 39.9 months in the Cabometyx arm versus 23 months in the placebo arm.

"Cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in previously untreated advanced renal cell carcinoma (aRCC): final results of COSMIC-313" by Dr. Laurence Albiges, et al., 

Patients with advanced renal cell carcinoma showed improved progression-free survival (PFS) with Cabometyx (cabozantinib) plus Opdivo (nivolumab) and Yervoy (ipilimumab) compared to placebo, as per the COSMIC-313 trial. The combination therapy demonstrated a PFS of 16.6 months versus 11.2 months for placebo, with no significant overall survival (OS) differences. M2-like macrophages were identified as predictors of OS, with the Cabometyx combination overcoming their tumor-promoting effects. Treatment-related side effects were more prevalent in the Cabometyx arm, leading to higher discontinuation rates.

Final results were consistent with previously conducted research in patients with advanced renal cell carcinoma treated with Cabometyx, Opdivo and Yervoy. 

Cabometyx Combo Maintains Progression-Free Survival Benefit in Advanced RCC

Palliative care consultations for patients with esophageal cancer at the end of life were associated with improved quality of life, reduced financial strain, and fewer intensive interventions.

Palliative care consultations helped patients with esophageal cancer at end-of-life experience better quality of life and less financial strain by reducing the need for intensive interventions, according to a poster presented at the 2025 ASCO Gastrointestinal Cancers Symposium.

The mean length of hospital stay was 7.5 days (plus or minus 11.3 days) for patients who received 

 and 8.9 days (plus or minus 14.9) for those who didn’t; and total charges were $97,879 (plus or minus $195,868) and $146,128 (plus or minus $321,830), respectively. Patients who received palliative care consultation had a Charlson Comorbidity Index of 9.4 (plus or minus 3.3) versus 9.1 (plus or minus 3.5) for patients who did not.

Of patients to receive and not to receive a palliative care consultation, 0.9% and 1.6%, respectively, underwent chemotherapy; 12.3% and 18% underwent blood transfusion; and 28.5% and 41.0% underwent mechanical ventilation.

“Some patients continue to receive burdensome interventions which significantly deteriorate quality of life,” Dr. Suriya Baskar, a second-year resident in the Internal Medicine Department at the Brooklyn Hospital Center, and lead investigator of the study, wrote in the presentation. “These findings highlight the importance of early integration of palliative care in [patients with esophageal cancer] with advanced disease.”

Palliative care: care given to help reduce pain and improve quality of life in patients with diseases like cancer. The goal of this care is to prevent or treat the symptoms of the disease and its side effects as early as possible.

Charlson Comorbidity Index: a tool used to predict the risk for death in a patient based on the presence of other health conditions. For example, a score of 9 indicates a high burden of comorbidity and is linked with a significantly increased risk for mortality.

Vasopressor: a medication that causes blood vessels to narrow as a treatment for low blood pressure.

In this study, a total of 17,745 patients were included; 10,370 of whom received palliative care consultation and 7,375 of whom did not. Patient data was gathered to identify all esophageal cancer hospitalizations between 2016 and 2020.

Of the patients indexed, 20% and 19.6% in the palliative consultation and no palliative consultation groups, respectively, were female. The median age was 67.58 (plus or minus 10.9) in both groups.

A non-significant difference was found in the use of vasopressor between those who received a palliative care consultation and those who did not, 8.1% versus 8%, respectively. There was, however, a significant difference in the rates of do-not-resuscitate orders between patients who did and did not receive palliative care consultations, 78.1% versus 43.2%, respectively.

“Esophageal cancer is an aggressive malignancy with a high global prevalence,” Baskar said. “Hospitalizations of [patients with esophageal cancer] at [end of life] with palliative care consultations received less aggressive interventions considerably improving [quality of life] while simultaneously reducing financial burden.”

The investigators also highlighted barriers to palliative care consultations, the impact of the timing of palliative care consultations on outcomes and the number of patients with esophageal cancer that are admitted to hospice at end of life as potential future avenues of research.

Impact of inpatient palliative care consultation on end-of-life care among patients with esophageal cancer. Dr. Suriya Baskar, et al. 

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Palliative care consultations for esophageal cancer patients at end-of-life significantly enhance quality of life and reduce financial burdens by minimizing intensive interventions. A study presented at the 2025 ASCO Gastrointestinal Cancers Symposium revealed that patients receiving palliative care had shorter hospital stays, lower total charges, and fewer aggressive treatments like chemotherapy and mechanical ventilation. The study, involving 17,745 patients, emphasized the importance of early palliative care integration. Future research may explore barriers to palliative care, timing of consultations, and hospice admissions for esophageal cancer patients.

End-of-life palliative care consultations may also ease financial strain for patients with esophageal cancer.

Palliative Care May Improve Quality of Life in Esophageal Cancer 

Neoadjuvant Keytruda given in a single cycle resulted in a pathological complete response rate of 44% in patients with deficient DNA mismatch repair colon cancer.

Neoadjuvant Keytruda (pembrolizumab) given in a single cycle was deemed efficacious and safe for patients with deficient DNA mismatch repair (dMMR) colon cancer, as shown in results from the phase 2 RESET-C trial presented at the 2025 ASCO Gastrointestinal Cancer Symposium.

A pathological complete response (pCR) was noted in 44% (95% CI, 33%-55%) of patients and a major pathological response (mPR) in 57% (95% CI, 46%-68%). For stage 1 or 3, the pCR rate was 61% and for stage 3 it was 33%.

At the survival follow-up date of December 2024, 70 patients had a minimum of one year of follow-up, 57 had a one-year CT scan done, two had died within 30 days of surgery and there were no instances of recurrence.

Grade 3 (severe) side effects were observed in 8% of patients, with 4% experiencing immune-related grade 3 side effects. Of those included were two patients with hepatitis and one patient with colitis. There were no grade 4 (life-threatening) or 5 (death) immune-related side effects noted.

Neoadjuvant: treatment given before a main treatment like surgery.

Deficient DNA mismatch repair: when the body’s natural system for correcting errors that occur during DNA replication malfunctions, which can lead to genomic instability.

Pathological complete response: the absence of any remaining invasive cancer cells in tissue samples removed during surgery after neoadjuvant therapy.

Major pathological response: a significant reduction in the number of viable cancer cells.

Grade 3a or above Clavien-Dindo: a surgical complication that requires some form of intervention, but not always under general anesthesia.

Ischemic bowel: when the intestines do not receive enough blood flow.

Overall survival: the time from diagnosis or the start of treatment when a patient with cancer is still alive.

In 31 patients (37%), there were 41 surgical complications observed. These included grade 3a or above Clavien-Dindo (eight patients), and post-operative deaths (two patients) at age 80 or above. These deaths were related to either gastric stress ulcer-related perforation (one patient) or ischemic bowel (one patient).

“Our next step is to integrate the results of the endoscopic evaluation, re-biopsies, and ctDNA aiming to develop a reliable response assessment tool to pave the path for a future organ preservation strategy,” Dr. Camilla Qvortrup, clinical associate professor at Rigshospitalet - Center for Cancer and Organ Disease in Denmark, stated during the presentation.

Of the 85 patients enrolled, all were given Keytruda and included in the safety analysis. One patient did not undergo surgery because of their own wishes, so 84 patients underwent surgery and were included in the efficacy analysis.

To be included, patients must have dMMR stage 1 to 3 colon cancer and have no contraindication for immunotherapy. The primary end point was pCR rate and secondary end points included safety, surgical complications, mPR and overall survival.

Patients were screened at diagnosis and then included if eligible. They were then given Keytruda followed by tumor restaging with a CT scan and colonoscopy. Patients then moved to surgery three to five weeks after completing Keytruda treatment with a CT scan as follow-up at one and three years.

“By integrating the results of the re-endoscopy, the biopsies after treatment, and ctDNA, we are aiming to develop a reliable response assessment tool to pave the path for a future organ preservation strategy,” Qvortrup stated.

The study posed to answer a few key questions for this disease state. Previously, neoadjuvant immune checkpoint inhibitors had shown positive results in dMMR colorectal cancer. However, the optimal duration of treatment and response evaluation had not yet been determined. Investigators believed that the use of a PD-1 inhibitor for single-cycle therapy would reduce toxicity and costs.

Single-cycle neoadjuvant pembrolizumab in patients with stage I-III MMR-deficient colon cancer: final analysis of the RESET-C study

Neoadjuvant pembrolizumab demonstrated efficacy and safety in dMMR colon cancer patients, as evidenced by the phase 2 RESET-C trial. A pathological complete response was achieved in 44% of patients, with a major pathological response in 57%. The study reported no recurrences and minimal severe side effects, with 8% experiencing grade 3 adverse events. Surgical complications occurred in 37% of patients, including two post-operative deaths. The trial aims to develop a reliable response assessment tool for future organ preservation strategies, addressing treatment duration and response evaluation challenges.

Neoadjuvant Keytruda for patients with deficient DNA mismatch repair colon cancer resulted in a pathological complete response rate of 44%. 

Ariana Pelosci

Opdivo Plus Cabometyx Safe, Effective in Advanced Renal Cell Carcinoma

Cabometyx Combo Maintains Progression-Free Survival Benefit in Advanced RCC

Palliative Care May Improve Quality of Life in Esophageal Cancer

Neoadjuvant Keytruda Shows Significant Benefit in dMMR Colon Cancer

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