Russ Conroy

Data from the KEYNOTE-B61 trial show tumor shrinkage in different types of kidney cancer, including papillary and chromophobe subtypes: © stock.adobe.com.

Updated results from the phase 2 KEYNOTE-B61 trial showed that combining Keytruda (pembrolizumab) with Lenvima (lenvatinib) continued to help shrink tumors and improve survival when used as a first treatment for people with advanced non-clear cell kidney cancer, according to data presented at the 

Among all evaluable patients who received Keytruda plus Lenvima (152 patients), the overall response rate was 50.6%, the disease control rate was 82.3% and the clinical benefit rate was 71.5%. Data showed complete responses in 10.1% of patients and partial responses in 40.5%.

The study treatment yielded an overall response rate of 53.8% in patients with papillary disease (93 patients), 31% in those with chromophobe histology (29 patients) and 66.7% in those with translocations (6 patients). Additionally, 50% and 77.8% of patients with unclassified (20 patients) and other histology (9 patients) experienced a response.

Any reduction in tumor burden occurred in 88.6% of all patients. Tumor burden reductions were observed in 91.4% of those with papillary disease, 75.9% of those with chromophobe histology, 95% of those with unclassified disease, 100% of those with translocations and 88.9% of those with other histologies. The median duration of response was 23.5 months.

The median progression-free survival was 17.9 months across the overall population, which included a progression-free survival rate of 39% at 24 months and 26% at 36 months. Additionally, the median progression-free survival was 17.7 months in the papillary subgroup and 11.3 months in the chromophobe subgroup. In each respective group, the 24-month progression-free survival rate was 35% and 44%, and the 36-month rate was 22% and 27%.

Across the overall population, the study treatment produced a median overall survival of 41.5 months, with overall survival rates of 67% at 24 months and 54% at 36 months. The median overall survival was 37.5 months in the papillary subgroup and was not reached in the chromophobe subgroup. The overall survival rates in each group were 65% versus 69% at 24 months, and 50% versus 62% at 36 months.

“After a minimum of 3 years of follow-up, Keytruda plus Lenvima continued to show durable antitumor activity and promising survival outcomes in the first-line setting for patients with advanced non-clear cell renal cell carcinoma,” lead study author Dr. Laurence Albiges, stated in the presentation. “As of now, this is one of our standards of care to treat patients including papillary, chromophobe or different histologies than non-clear cell renal cell carcinoma. We're excited that this has changed the paradigm for our patients.”

Albiges is head of the Department of Oncology at Institut Gustave Roussy.

In the single-arm KEYNOTE-B61 trial, 158 patients were assigned to receive Keytruda at 400 mg intravenously every 6 weeks for a maximum of 18 cycles plus Lenvima at 20 mg orally once daily.

The trial’s primary end point was overall response rate per blinded independent central review using RECIST 1.1 criteria. Secondary end points included duration of response, progression-free survival, overall survival and safety.

Patients 18 years and older with histologically confirmed stage 4 non-clear cell renal cell carcinoma, measurable disease per RECIST 1.1 guidelines, a Karnofsky performance status of 70% or higher and no prior therapy for advanced disease were eligible for enrollment on the trial. Having adequately controlled blood pressure with or without antihypertensive medications as well as adequate organ function were additional requirements for study entry.

The median patient age was 60 years. The most common histology was papillary (58.9%) followed by chromophobe (18.4%), unclassified (12.7%), other (5.7%), translocated (3.8%) and medullary (0.6%). Additionally, 12% of patients had sarcomatoid features and 63.3% had an intermediate or poor International Metastatic Renal Cell Carcinoma Database Consortium risk.

Investigators administered any subsequent therapy to 38.6% of the study population. The most common types of subsequent treatment included any VEGF or VEGFR inhibitor (35.4%), any mTOR inhibitor (8.9%) and any PD-(L)1 inhibitor (6.3%).

Any-grade side effects affected 99.4% of patients and 77.2% experienced grade 3 to 5 toxicities. Additionally, 31% of side effects resulted in treatment discontinuation, 48.1% had serious side effects and 6.3% had side effects leading to death. Any-grade and grade 3 or higher treatment-emergent side effects affected 96.2% and 60.1% of patients, respectively, and any-grade and grade 3 or higher immune-mediated side effects occurred in 58.9% and 10.1%.

The most common treatment-emergent side effects included hypertension (57.6%), diarrhea (50%), hypothyroidism (41.1%), proteinuria (34.2%), fatigue (31%), palmar-plantar erythrodysesthesia syndrome (30.4%), dysphonia (29.1%) and diminished appetite (27.2%). Other treatment-emergent side effects included nausea (25.3%), decreased weight (22.8%), asthenia (22.2%), arthralgia (19.6%), stomatitis (19.6%), mucosal inflammation (15.2%) and pruritus (15.2%).

“Pembrolizumab plus lenvatinib for previously untreated advanced non–clear cell renal cell carcinoma: 3-year follow-up of the phase 2 KEYNOTE-B61 study,” by Dr. Laurence Albiges. Presented at the 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA. Abstract 1.

Pembrolizumab plus lenvatinib for first-line advanced/​metastatic non-clear cell renal cell carcinoma (1L nccRCC) (MK-3475-B61) (KEYNOTE-B61). ClinicalTrials.gov. Updated February 17, 2025. Accessed July 21, 2025.

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Articles

The phase 2 KEYNOTE-B61 trial demonstrated that combining Keytruda (pembrolizumab) with Lenvima (lenvatinib) as a first-line treatment for advanced non-clear cell kidney cancer significantly improved tumor shrinkage and survival rates. The trial reported an overall response rate of 50.6% and a disease control rate of 82.3%. The median progression-free survival was 17.9 months, and the median overall survival was 41.5 months. Despite promising results, the treatment was associated with high rates of side effects, including serious and treatment-discontinuing toxicities.

Data from the KEYNOTE-B61 trial show tumor shrinkage in different types of kidney cancer, including papillary and chromophobe subtypes. 

Clinical Trial Confirms Keytruda and Lenvima Benefit in Kidney Cancer 

Welireg improved quality-adjusted survival time versus Afinitor in advanced renal cell carcinoma, extending progression-free survival and reducing side effects.

Welireg (belzutifan) improved quality-adjusted survival time significantly over Afinitor (everolimus) in patients with advanced renal cell carcinoma, according to a quality-adjusted time without symptoms or toxicity analysis from the phase 3 LITESPARK-005 trial presented at the 

. This finding highlights Welireg’s potential to extend survival while reducing side effects for patients with advanced kidney cancer.

Based on the main analysis, in which toxicity accounted for grade 3 (severe)/4 (life-threatening) side effects, the mean Q-TWiST was 17.47 months among patients who received Welireg (374 patients) versus 14.81 months among those who received Afinitor (372 patients). The relative gain in Q-TWiST with Welireg, defined as the absolute Q-TWiST difference divided by mean overall survival (OS) for the Afinitor arm, was 11.32% in the main analysis.

The sensitivity analysis, which included grade 1 (mild) to 4 serious side effects, showed a mean Q-TWiST of 17.50 months in the Welireg arm versus 15.03 months in the Afinitor arm. Data highlighted a relative Q-TWiST gain of 10.50% in the sensitivity analysis.

“In conclusion, Welireg outperformed Afinitor from a response and a progression-free-survival [PFS] perspective. The toxicity profile was distinct, the quality of life was better, and so was the TWiST and the Q-TWiST analysis,” lead study investigator, Dr. Thomas Powles stated in the presentation. “This [Q-TWiST analysis] does help patients and doctors make decisions. I quite like this type of exploratory analysis, and I'm happy to be involved in future projects with it.”

Powles is a professor of genitourinary oncology, lead for Solid Tumor Research, and director of Barts Cancer Institute at St. Bartholomew’s Hospital, Queen Mary University of London.

As part of this analysis, investigators divided patient survival time following randomization into three mutually exclusive states: investigator-assessed time with grade 3/4 toxicity before disease progression (TOX), time without symptoms and progression of grade 3/4 toxicity (TWiST), and time from progression until death (REL). Investigators calculated Q-TWiST as the sum-product of restricted mean time spent in the individual states and state-specific utility weights. Additionally, standard utility weights used in literature — one for TWiST as well as 0.5 for TOX and REL — were considered, and threshold utility analysis was performed to determine the impact of the differing health state utility.

The study authors summarized the treatment effects as differences in restricted mean time spent in each state; the difference in Q-TWiST; and the relative gain in Q-TWiST, or the absolute Q-TWiST difference divided by mean OS in the Afinitor arm. Use of nonparametric bootstrapping method was involved for generating 95% confidence intervals for the treatment differences related to the health states and Q-TWiST.

In the multicenter, open-label phase 3 LITESPARK-005 trial, patients were randomly assigned 1:1 to receive Welireg at 120 milligrams (mg) or Afinitor at 10 mg orally once daily until progressive disease or unacceptable toxicity.

The trial’s dual primary end points were PFS and OS. Secondary end points included the objective response rate, duration of response and safety.

In the main analysis, the mean TOX time was 1.45 months in the Welireg arm versus 1.22 months in the Afinitor arm. Despite a numerically longer time in TOX among those in the Welireg arm, data showed significantly longer time in TWiST with Welireg at a mean of 10.73 months versus 6.07 months with Afinitor, which was driven by prolonged periods without progression.

Prior safety data showed that the most common any-grade side effects in the Welireg and Afinitor arms, respectively, included anemia (83.1% versus 57.2%), fatigue (32.3% versus 25.8%), nausea (18.5% versus 12.2%), edema peripheral (17.2% versus 18.1%), and constipation (16.9% versus 8.3%).

“Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of Welireg versus Afinitor in previously treated advanced renal cell carcinoma” by Dr. Powles, et al., Presented at the 2025 Kidney Cancer Research Summit.

“Welireg versus Afinitor for advanced renal cell carcinoma” by Dr. Choueiri, et al., New England Journal of Medicine.

Welireg (belzutifan) demonstrated a significant improvement in quality-adjusted survival time over Afinitor (everolimus) for advanced renal cell carcinoma patients, as shown in the phase 3 LITESPARK-005 trial. The analysis revealed a mean Q-TWiST of 17.47 months for Welireg compared to 14.81 months for Afinitor, with a relative gain of 11.32%. Sensitivity analysis confirmed these findings, showing a 10.50% relative gain. Welireg's distinct toxicity profile and better quality of life outcomes suggest its potential as a superior treatment option for this patient population.

Welireg Improves Quality-Adjusted Survival Time in Advanced RCC

Adding Zyprexa to ondansetron cut nausea and vomiting safely in abdominal/pelvic radiation with low-emetogenic capecitabine.

Among patients receiving abdominal/pelvic radiotherapy or concurrent chemoradiation with low-emetogenic oral capecitabine, the addition of Zyprexa (olanzapine) to standard antiemetics may safely and effectively prevent radiation-induced nausea and vomiting (RINV), according to data from a phase 3 placebo-controlled trial presented at 

Safety data from the trial revealed that among patients assigned to receive 5 mg of Zyprexa (148 patients) versus placebo (153 patients), nausea occurred in 14.2% and 83.6%, respectively. Additionally, the incidence of grade 2 (moderate) or greater nausea was 67.3% versus 7.4% with placebo versus olanzapine.

Additionally, vomiting was also reduced with olanzapine; 25.5% of the placebo group and 4.1% of the experimental group experienced any-grade vomiting. Furthermore, the incidence of grade 2 or higher vomiting was 7.8% versus 1.3% in each respective arm. Further data showed that the addition of Zyprexa also reduced the total number of vomiting episodes among patients receiving radiotherapy, with 16.3% of the standard group experiencing 1 to 15 episodes versus 2% of the experimental group; 9.2% versus 2% of each arm experienced more than 15 episodes.

The incidence of grade 2 or higher nausea was also significantly lower for patients across a variety of cancer types. In patients with endometrial cancer, 85.7% of the placebo group and 2.8% of the experimental group experienced grade 2 or higher nausea. The respective rates for endometrial, stomach/pancreatic, and prostate cancers were 92.9% versus 0%, 100% versus 40%, and 19.1% versus 8.7%.

Radiation-induced nausea and vomiting (RINV): nausea and vomiting caused by radiation therapy, particularly in abdominal or pelvic areas.

Antiemetics: medications used to prevent or treat nausea and vomiting.

Quality of life (QOL): a measure of a patient's overall well-being and ability to perform daily activities.

“The addition of 5 mg Zyprexa to standard ondansetron therapy is found to be safe and effective for preventing nausea and vomiting in patients receiving abdominal/pelvic radiation therapy, and those undergoing concurrent chemoradiation with low-emetogenic oral capecitabine,” Meenu Vijayan, MPharm, assistant professor at the Amrita School of Pharmacy, said in the presentation. “Our study was a single-center study. Future studies involving multiple centers and a large number of patients are recommended to corroborate our findings.”

Patients 18 years or older who were receiving abdominal/pelvic radiotherapy and were previously radiotherapy naïve were randomly assigned to receive 4 milligrams of twice daily ondansetron (Zofran) and either 5 mg of oral daily Zyprexa or matching placebo. The study assessed efficacy and safety using the Common Terminology Criteria for Adverse Events (CTCAE) scale, including a nausea and vomiting diary, as well as anxiety and depression using the Hamilton Rating Scale, and quality of life (QOL) using the EORTC QLQ C30 questionnaire.

Patients in the standard and experimental groups, respectively, had a mean age of 63.82 versus 62.32, 58.2% versus 62.8% were males, and 67.3% versus 70.3% had comorbidities. Furthermore, 18.3% versus 19.6% had a history of smoking, 24.8% versus 23% had a history of alcohol, and 50.3% versus 54.7% had a family history of cancer in respective groups. In total, 56.9% versus 53.4% of each group received concurrent capecitabine and 30.7% versus 31.1% received hormone therapy.

The most common cancer types in the standard and experimental groups included rectal cancer (50.3% versus 48.6%), prostate cancer (30.7% versus 31.1%), and endometrial cancer (9.2% versus 9.5%). The most common type of radiotherapy was image-guided radiation therapy (88.9% versus 83.1%) and the most common radiotherapy site was the pelvic area (91.5% versus 93.2%). Patients in each group received a mean dose of 222.58 Gy/day versus 222.01 Gy/day, with a mean duration of 23.67 days versus 23.76 days.

Additional findings from the trial revealed that treatment with Zyprexa reduced mean anxiety scores versus placebo. A similar trend was observed for mean depression scores. Additionally, mean changes in QOL score in the functional scale from baseline to radiotherapy universally favored the experimental, particularly for emotional functioning. This trend was observed in the symptom scale as well, with significant improvements noted in nausea/vomiting, insomnia, and loss of appetite.

“Phase 3 randomized placebo-controlled trial on repurposing Zyprexa for prevention of radiotherapy-induced nausea and vomiting (RINV)” by Dr. M. Vijayan, et al., 

The addition of Zyprexa (olanzapine) to standard antiemetic therapy significantly reduces radiation-induced nausea and vomiting (RINV) in patients undergoing abdominal/pelvic radiotherapy or concurrent chemoradiation with capecitabine. A phase 3 trial demonstrated that Zyprexa decreased the incidence and severity of nausea and vomiting compared to placebo. The study also showed improvements in anxiety, depression, and quality of life metrics. While the trial was single-center, further multi-center studies are recommended to validate these findings and potentially establish Zyprexa as a standard adjunctive treatment for RINV.

Zyprexa Added to Standard Antiemetics Reduces Nausea, Vomiting in Radiation

The COCOON dermatologic management regimen reduced QOL  impact of Rybrevant/Lazcluze vs SOC in EGFR-mutated NSCLC: © stock.adobe.com.

The COCOON dermatologic management regimen significantly reduced the quality-of-life impact associated with Rybrevant (amivantamab-vmjw) plus Lazcluze (lazertinib) treatment versus the standard-of-care dermatologic management approach in patients with EGFR-mutated non-small cell lung cancer (NSCLC), according to phase 2 findings from the COCOON trial, which were shared at the 

A lower average Skindex-16 total score was reported in patients who received COCOON DM versus those with standard-of-care dermatologic management at day 15 of cycle three. Additionally, use of COCOON DM correlated with improvements in the functioning, emotional and symptoms subscales.

No moderate or severe symptoms on the Patient Global Impression of Severity (PGI-S) scale occurred among patients who received COCOON DM at day 15 of cycle three. The rates of patients reporting no symptoms in the COCOON DM and standard-of-care dermatologic management arms, respectively, were 21% versus 7% for rash, 23% versus 7% for skin conditions and 27% versus 16% for nail infections.

“At this analysis, which evaluated the first 12 weeks of treatment, [patients] in the COCOON DM arm experienced lower severity of dermatologic symptoms and a reduced impact on quality of life than [patients] in the standard-of-care dermatologic management arm,” lead study author Jill Feldman, founder of EGFR Registers, a patient advocacy group in Deerfield, Illinois, wrote with coauthors. “Substantial and consistent separation favoring COCCON DM was observed in all postbaseline Skindex-16 subscales. Most [patients] in the COCOON DM arm reported mild or no dermatologic symptoms. This benefit was consistently observed across the first [approximately] 10 weeks of treatment.”

Investigators of the phase 2 COCOON trial prospectively assessed a novel DM regimen for preventing moderate to severe EGFR-associated side effects that may occur following treatment with amivantamab plus lazertinib. In this analysis, investigators highlighted patient-reported outcomes from the first 12 weeks of therapy.

A total of 201 patients were randomly assigned to receive amivantamab/lazertinib plus COCOON DM (99 patients) or standard-of-care dermatologic management (102 patients). The COCOON regimen consisted of oral doxycycline or minocycline for 12 weeks followed by topical clindamycin lotion each day on the scalp, starting at week 13 for nine months; chlorhexidine on the nails each day for 12 months; and ceramide-based moisturizer applied to the body and face at least each day for 12 months. In the standard-of-care dermatologic management arm, patients received general skin prophylaxis based on local practice and relative treatment, including corticosteroids and systemic antibiotics.

The study’s primary end point was the incidence of grade 2 or higher dermatologic side effects within the first 12 weeks following the beginning of amivantamab/lazertinib therapy. The select secondary end points were PROs per Skindex-16 and PGI-S after 12 weeks of follow-up.

The Skindex-16 questionnaire was validated to determine how skin conditions impact quality of life based on the subscales of functioning, emotional, and symptoms. The PGI-S was a patient-reported 4-point rating scale — none, mild, moderate, or severe symptoms — used to evaluate the severity of rashes, skin conditions, and nail infections over time.

Those with locally advanced or metastatic, treatment-naïve NSCLC harboring documented EGFR exon 19 deletions or 

 mutations were eligible for enrollment on the study. An ECOG performance status of 0 or 1 was an additional requirement for study entry.

 for patients with locally advanced or metastatic EGFR

mutated NSCLC based on findings from the phase 3 MARIPOSA trial.

“Dermatologic prophylaxis and impact on patient-reported outcomes in first-line EGFR-mutant advanced NSCLC treated with amivantamab plus lazertinib: Results from the phase 2 COCOON trial” by Dr. J. Feldman, et al., 2025 ASCO Annual Meeting.

The COCOON trial demonstrated that the COCOON dermatologic management regimen significantly improved quality of life for patients with EGFR-mutated NSCLC treated with amivantamab and lazertinib, compared to standard dermatologic care. Patients receiving COCOON DM reported lower Skindex-16 scores, indicating better functioning, emotional well-being, and fewer symptoms. No moderate or severe symptoms were observed on the PGI-S scale in the COCOON DM group. The trial involved 201 patients and highlighted the regimen's effectiveness in reducing dermatologic side effects, with substantial benefits observed within the first 12 weeks of treatment.

The COCOON dermatologic management regimen reduced the quality-of-life impact of Rybrevant/Lazcluze vs SOC treatment in patients with EGFR-mutated NSCLC. 

Russ Conroy

Clinical Trial Confirms Keytruda and Lenvima Benefit in Kidney Cancer

Welireg Improves Quality-Adjusted Survival Time in Advanced RCC

Zyprexa Added to Standard Antiemetics Reduces Nausea, Vomiting in Radiation

COCOON Regimen Eases Dermatologic Side Effects After Treatment in EGFR+ NSCLC

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