Previously, when Germans wanted to point out how crazy something is, they would naturally use German and say “Das ist verrückt.” Young Germans, however, now prefer to say, “Das crazy.”
Whether you’re surprised, speechless, want to make an ironic…
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Almost as harmful as alcohol: Top US cardiologist warns against a hidden danger that could turn kids into diabetic adults with fatty liver
US-based cardiologist Dr. Pradip Jamnadas, founder and medical director of Cardiovascular Interventions in Central Florida, has issued a striking warning about the hidden dangers of sugar. In a recent YouTube video, he cautioned that sugary…Continue Reading
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Rizwan ‘likely to be replaced’ as PCB mulls ODI captaincy change
Pakistan ODI captain Mohammad Rizwan speaks during a press conference regarding the ICC Champions Trophy, in Karachi, February 18, 2025. — Online - Mike Hesson ‘initiates’ talks on captaincy change.
- 2027 ODI World…
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Best Credit Cards for Travel Insurance
Booking travel is expensive these days, from the cost of trains or planes to paying for your luggage, lodgings and more. It’s important to have a backup plan in case things take a turn for the worst.
Booking your journey with a credit card that has travel insurance can ensure you’re covered in a number of different events. While many of these cards offer similar and overlapping benefits, some are better than others.
Below, we cover the best credit cards for travel protections and how they can provide you with peace of mind.
Best Credit Cards for Travel Protection
Best for trip cancellation and interruption insurance
The Chase Sapphire Preferred® Card packs a punch for a $95 annual fee card, offering annual travel credits, comprehensive travel protections and more.
- You can transfer rewards to all of Chase’s travel partners including World of Hyatt, Southwest Rapid Rewards and many more
- Long list of travel and shopping protections
- $50 annual Chase Travel hotel credit
- Has an annual fee
- Requires a high credit score
Highlights
Highlights shown here are provided by the issuer and have not been reviewed by CNBC Select’s editorial staff.
- Earn 75,000 bonus points after you spend $5,000 on purchases in the first 3 months from account opening.
- Enjoy benefits such as 5x on travel purchased through Chase TravelSM, 3x on dining, select streaming services and online groceries, 2x on all other travel purchases, 1x on all other purchases
- Earn up to $50 in statement credits each account anniversary year for hotel stays through Chase TravelSM
- 10% anniversary points boost – each account anniversary you’ll earn bonus points equal to 10% of your total purchases made the previous year.
- Count on Trip Cancellation/Interruption Insurance, Auto Rental Collision Damage Waiver, Lost Luggage Insurance and more.
- Complimentary DashPass which unlocks $0 delivery fees & lower service fees for a min. of one year when you activate by 12/31/27. Plus, a $10 promo each month on non-restaurant orders.
- Member FDIC
Balance transfer fee
Either $5 or 5% of the amount of each transfer, whichever is greater
Additional travel insurance perks: The Sapphire Preferred also comes with primary auto rental coverage, baggage delay insurance, lost luggage reimbursement, roadside assistance, travel accident insurance, travel and emergency assistance and trip delay insurance.
Best for trip delay coverage
The Chase Sapphire Reserve® is a standout premium credit card with plenty of luxury perks and statement credits to justify its annual fee.
- Access over 1,300 airport lounges worldwide with a complimentary Priority PassTM Select membership, plus every Chase Sapphire Lounge® by The Club with two guests.
- Up to $300 in annual travel credit each account anniversary year
- You can transfer rewards to all of Chase’s travel partners including World of Hyatt, Southwest Rapid Rewards and many more
- Top-tier travel and shopping protections
- High annual fee
- Requires a high credit score
Highlights
Highlights shown here are provided by the issuer and have not been reviewed by CNBC Select’s editorial staff.
- Earn 125,000 bonus points after you spend $6,000 on purchases in the first 3 months from account opening.
- Get more than $2,700 in annual value with Sapphire Reserve.
- Earn 8x points on all purchases through Chase TravelSM, including The EditSM and 4x points on flights and hotels booked direct. Plus, earn 3x points on dining worldwide & 1x points on all other purchases
- $300 annual travel credit as reimbursement for travel purchases charged to your card each account anniversary year.
- Access over 1,300 airport lounges worldwide with a complimentary Priority PassTM Select membership, plus every Chase Sapphire Lounge® by The Club with two guests. Plus, up to $120 towards Global Entry, NEXUS, or TSA PreCheck® every 4 years
- Get up to $150 in statement credits every six months for a maximum of $300 annually for dining at restaurants that are part of Sapphire Reserve Exclusive Tables.
- Count on Trip Cancellation/Interruption Insurance, Auto Rental Coverage, Lost Luggage Insurance, no foreign transaction fees, and more.
- Get complimentary Apple TV+, the exclusive streaming home of Apple Originals. Plus Apple Music — all the music you love, across all your devices. Subscriptions run through 6/22/27 — a value of $250 annually
- Member FDIC
Balance transfer fee
Either $5 or 5% of the amount of each balance transfer, whichever is greater
Additional travel insurance perks: The Sapphire Reserve also comes with primary auto rental coverage, baggage delay insurance, emergency evacuation and transportation benefits, emergency medical and dental benefits, lost luggage reimbursement, roadside assistance, travel accident insurance, travel and emergency assistance services, and trip cancellation and interruption insurance.
Best for auto rental coverage
The Capital One Venture X Rewards Credit Card is a premium credit card with a myriad of benefits and a lower annual fee than other high-end cards with similar features.
- Annual $300 credit for bookings through Capital One Travel
- 10,000 bonus miles after every card anniversary
- Unlimited complimentary access to 1,300+ airport lounges, including Capital One Lounge locations
- Long list of valuable travel and shopping protections, including return protection, rental car coverage and trip delay reimbursement (Benefit(s) only available to accounts approved for the Visa Infinite card. Terms apply.)
- Limited bonus spending categories compared to other premium credit cards
- High annual fee
- High credit score requirement (excellent credit)
Highlights
Highlights shown here are provided by the issuer and have not been reviewed by CNBC Select’s editorial staff.
- Earn 75,000 bonus miles when you spend $4,000 on purchases in the first 3 months from account opening, equal to $750 in travel
- Receive a $300 annual credit for bookings through Capital One Travel, where you’ll get Capital One’s best prices on thousands of trip options
- Get 10,000 bonus miles (equal to $100 towards travel) every year, starting on your first anniversary
- Earn unlimited 10X miles on hotels and rental cars booked through Capital One Travel and 5X miles on flights and vacation rentals booked through Capital One Travel
- Earn unlimited 2X miles on all other purchases
- Enjoy access to 1,300+ lounges worldwide, including Capital One Lounge locations and Priority Pass™ lounges, after enrollment
- Use your Venture X miles to easily cover travel expenses, including flights, hotels, rental cars and more. You can even transfer your miles to your choice of 15+ travel loyalty programs
- Enjoy a $100 experience credit and other premium benefits with every hotel and vacation rental booked from the Premier Collection
- Receive up to a $120 credit for Global Entry or TSA PreCheck®
Balance transfer fee
$0 at the Transfer APR, 4% of the amount of each transferred balance that posts to your account at a promotional APR that Capital One may offer to you
Foreign transaction fees
Additional travel insurance perks: Alongside the Venture X card’s auto rental insurance, it offers lost luggage reimbursement, trip delay reimbursement, trip cancellation and interruption insurance, travel and emergency assistance and travel accident insurance.
Best for lost or damaged baggage
The Citi Strata Elite℠ Card aims to brings premium restaurant rewards and travel benefits to users, including an annual hotel benefit of $300.
- High rewards rate on travel
- 6X on restaurants
- Can transfer points to American Airlines at a 1:1 rate
- Up to $200 annual splurge credit
- High annual fee
- Limited rewards categories
Highlights
Highlights shown here are provided by the issuer and have not been reviewed by CNBC Select’s editorial staff.
- For a limited time, earn 100,000 bonus Points after spending $6,000 in the first 3 months of account opening.
- Earn 12 Points per $1 spent on Hotels, Car Rentals, and Attractions booked on cititravel.com and 6 Points per $1 spent on Air Travel booked on cititravel.com
- Earn 6 Points per $1 spent at Restaurants including Restaurant Delivery Services on CitiNights℠ purchases, every Friday and Saturday from 6 PM to 6 AM ET. Earn 3 Points per $1 spent any other time
- Earn 1.5 Points per $1 spent on All Other Purchases
- Up to $300 Annual Hotel Benefit: Each calendar year, enjoy up to $300 off a hotel stay of two nights or more when booked through cititravel.com.
- No Foreign Transaction Fees
Balance transfer fee
Balance transfer fee applies with this offer 5% of each balance transfer; $5 minimum.
Additional travel insurance perks: Other travel insurance benefits of the Citi Strata Elite include secondary auto rental coverage (primary outside your country of residence), trip delay protection and trip cancellation and interruption protection.
Best for lower credit scores
Choice Rewards World Mastercard®
On First Tech Federal Credit Union’s site
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Rewards
Earn 2X points on groceries, gas, electronics, medical, household goods and telecommunications, 1X points on all other purchases
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Welcome bonus
Earn 20,000 points when you spend $3,000 in the first 60 days from account opening
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Annual fee
-
Intro APR
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Regular APR
-
Balance transfer fee
-
Foreign transaction fee
-
Credit needed
Pros
- Low APR
- No annual fee
- Popular 2X rewards categories
Cons
- Below average amount of time to earn the card’s welcome bonus
- No option to transfer points to travel programs
Standout travel insurance benefit: The Choice Rewards World Mastercard isn’t a premium travel card, but it’s easier to get, has no annual fee and is still loaded with travel insurance perks. So if you can’t qualify for the top-tier travel credit cards or don’t want to shell out hundreds of dollars every year for a credit card with travel insurance, this is a great option.
Additional travel insurance perks: The Choice Rewards Mastercard offers baggage delay coverage, trip cancellation coverage, secondary MasterRental car coverage, travel accident insurance and lost or damaged luggage insurance.
Best credit cards for travel protection
Credit card Annual fee CNBC Select’s pick for Additional travel insurance benefits Offers a welcome bonus Chase Sapphire Preferred® Card $95 Best for trip cancellation and interruption insurance Auto rental coverage, baggage delay insurance, lost luggage reimbursement, roadside dispatch, travel accident insurance, travel and emergency assistance services, trip delay reimbursement and trip cancellation and interruption insurance Yes Chase Sapphire Reserve® Credit Card $795 Best for trip delay reimbursement Auto rental coverage, baggage delay insurance, emergency evacuation and transportation, lost baggage reimbursement, roadside assistance, trip delay reimbursement, travel accident insurance, travel and emergency assistance services, emergency medical and dental benefits and trip cancellation and interruption insurance Yes Capital One Venture X Rewards Credit Card $395 Best for auto rental coverage Auto rental coverage, lost baggage insurance, travel accident insurance, trip delay coverage, travel and emergency assistance services and trip cancellation and interruption insurance Yes Citi Strata Elite℠ Card $595 Best for lost/damaged baggage Auto rental coverage, lost/damaged baggage insurance, trip delay coverage and trip cancellation insurance Yes First Tech Credit Union Choice Rewards World Mastercard® $0 Low credit MasterRental auto coverage, lost/damaged baggage insurance, baggage delay insurance, travel accident coverage and trip cancellation insurance Yes How to use credit card travel insurance
The first step toward using your credit card travel insurance is making sure that you’re covered under its policy. Some cards offer all types of travel insurance, while others just cover one specific area, so it’s best to check your benefits before making a claim.
For most claims, you’ll be required to provide documents to verify your claim, that could include:
- Proof of trip delay, interruption or cancellation
- Receipts for any expenses relating to the claim (hotel stays, food bills, etc.)
- Medical bills and hospital records
- Police reports
- A loss report from the airline or other transportation provider
- A list of what was in your luggage and its value
Many credit cards also require you to file your claims within a certain window, which will typically range from 20 to 60 days. You can often file online via your credit card’s benefit provider website or you can call to get the process started.
Is credit card travel insurance enough?
For many occasions, yes, the travel insurance provided by your credit card will likely be enough. But there might be times in when the coverage doesn’t apply or it doesn’t meet all your needs.
While credit card travel insurance can come in handy in many ways, it’s important to plan ahead and know your card’s limitations, so you can have a backup where needed.
FAQs
Do credit cards include travel insurance?
Yes, depending on the card you have, it could provide you with travel insurance. Travel insurance is a common benefit for premium cards that have annual fees. However, there are credit cards that offer these perks with no annual fee.
How do I know if I have travel insurance through my credit card?
The best way to know if your credit card provides travel insurance is to check the card’s benefits guide. Make sure you fully understand your card’s benefits and when they will and won’t apply to your travel bookings.
What does credit card travel insurance actually cover?
The exact coverage varies, but a few common insurance benefits are trip cancellation and interruption, lost or damaged baggage, trip delay, and theft or damage to rental cars.
Why trust CNBC Select?
At CNBC Select, our mission is to provide our readers with high-quality service journalism and comprehensive consumer advice so they can make informed decisions with their money. Every credit card list is based on rigorous reporting by our team of expert writers and editors with extensive knowledge of credit card products. While CNBC Select earns a commission from affiliate partners on many offers and links, we create all our content without input from our commercial team or any outside third parties, and we pride ourselves on our journalistic standards and ethics. See our methodology for more information on how we choose the best credit cards for travel protection.
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Our methodology
To determine which cards offer the best travel protection, CNBC Select analyzed over 250 major credit cards issued through FDIC-insured banks and NCUA-insured credit unions that are widely available in the U.S.
We compared each card on a range of travel protection features, such as what types of trips are covered and what conditions have to be met for you to take advantage of the benefit. We also considered overall cost, factoring in annual fees, welcome bonuses, introductory and standard APRs, balance transfer fees and foreign transaction fees. We also considered the application process when available (e.g., is there a credit pull or required credit score).
We also considered CNBC Select audience data when available, such as general demographics and engagement with our content and tools.
Catch up on CNBC Select’s in-depth coverage of credit cards, banking and money, and follow us on TikTok, Facebook, Instagram and Twitter to stay up to date.
Editorial Note: Opinions, analyses, reviews or recommendations expressed in this article are those of the Select editorial staff’s alone, and have not been reviewed, approved or otherwise endorsed by any third party.
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Belzutifan Plus Pembrolizumab and Lenvatinib Demonstrates Potential in Advanced Clear Cell RCC
Treatment with belzutifan (Welireg) plus pembrolizumab (Keytruda) and lenvatinib (Lenvima) improved efficacy outcomes compared with multiple other pembrolizumab-based triplet regimens in patients with advanced clear cell renal cell carcinoma (ccRCC), according to findings from substudy 3A of the phase 1/2 KEYMAKER-U03 trial (NCT04626479) presented at the
2025 ESMO Congress .Providing the background for the study, Cristina Suarez Rodriguez, MD, PhD, of Vall d’Hebron University Hospital, Barcelona, Spain, said, “First-line triplet regimens adding novel mechanisms of action to standard doublet therapy may be a promising approach for advanced clear cell renal cell carcinoma…The potent and selective HIF-2α inhibitor belzutifan is a treatment for advanced RCC following prior anti-PD-(L1) and VEGFR-TKI therapy, and may be a highly suitable candidate for novel triplet therapy in the first-line setting.”
For substudy 3A (NCT04626479) of the umbrella phase 1/2 KEYMAKER-U03 trial, investigators sought to evaluate novel pembrolizumab-based regimens as first-line treatment for advanced ccRCC.
“The study employed an adaptive design in which experimental arms were added and/or inactivated on a rolling basis with a continuous enrolling reference arm. Experimental arms each had a safety lead-in phase of 10 patients,” Suarez Rodriguez explained.
Patients with histologically confirmed locally advanced or metastatic ccRCC as measurable by RECIST v1.1, no prior systemic therapy for advanced RCC, and a KPS score of at least 70% were eligible for the study. Following the safety lead-in phase, the study entered the randomized phase. In this phase, patients were randomly assigned to 2:1 to 1 of 5 arms. Arm 1 included coformulated favezelimab/pembrolizumab 800mg/200 mg intravenously every 3 weeks, and lenvatinib 20 mg orally once daily. Arm 2 included coformulated vibostolimab/pembrolizumab 200/200 mg IV every 3 weeks plus belzutifan 120 mg orally once daily. Arm 3 included coformulated quavonlimab/pembrolizumab 25 mg/400 mg IV every 6 weeks plus lenvatinib 20 mg orally once daily. Arm 4 included belzutifan 120 mg orally once daily plus pembrolizumab 400 mg IV every 6 weeks, plus lenvatinib 20 mg orally once daily. A concurrent reference arm included pembrolizumab 400 IV every 6 weeks plus lenvatinib 20 mg orally once daily.
Primary end points were overall responsive rate (ORR) as measured by RECIST v1.1 by blinded independent central review (BICR), as well as safety. Secondary end points included duration of response (DOR) and progression-free survival by RECIST v1.1 by BICR, as well as overall survival (OS).
Suarez Rodriguez reported ORR for the arms as follows:
• Arm 1: At a median follow-up of 39.2 months (range, 28.8-44.6 months), ORR was 62.7% (95% CI: 48.1-75.9).
• Arm 2: At a median follow-up of 16.4 months (range, 11.8-23.4 months), ORR was 42.5% (95% CI: 31.5-54.1).
• Arm 3: At a median follow-up of 22.1 months (range, 13.5-40.6 months), ORR was 71.3% (95% CI: 60.0-80.8).
• Arm 4: At a median follow-up of 23.4 months (range, 14.1-41.0 months), ORR was 77.5% (95% CI: 66.8-86.1).
• Reference arm: At a median follow-up of 21.2 months (range, 11.9-44.4 months), ORR was 80.6% (95% CI: 68.6-89.6).
Complete response was observed in 5 (9.8%), 4 (5.0%), 5 (6.3%), 10 (12.5%), and 4 (6.5%) patients across the respective arms.
In arm 1, DOR and PFS were found to be numerically similar to the reference arm, Suarez Rodriguez reported. The treatment regimen of arm 2 was found to be not superior to the reference arm. For arm 3, median DOR was 25.0 months (range, 2.4-37.1+ months) in arm 3 and 25.6 months (range, 1.4+-27.6 months) in the reference arm.
Arm 4 “showed a median duration of response of 33 months vs 26 months in the reference arm,” Suarez Rodriguez said. Median PFS was 31.8 months (95% CI: 26.3-NR) in arm 4 vs 20.8 months (95% CI: 12.4-29.0) in the reference arm (HR, 0.45, 95% CI: 0.25-0.83). OS was not reached in either arm.
Suarez Rodriguez also discussed safety across the regimens. Arm 1 had the highest incidence of grade 3 or higher adverse events (AEs) (86.9%), followed by arm 3 (73.3%), the reference arm (71.0%), arm 4 (70.0%), and arm 2 (68.9%). Arm 1 had the highest rate of treatment-related AEs (37.7%), followed by arm 3 (34.4%), arm 2 (31.1%), the reference arm (30.6%), and arm 4 (24.4%). Serious treatment-related AEs were highest in arm 1 (36.1%) followed by arm 3 (34.4%), the reference arm (30.6%), arm 2 (27.8%), and arm 4 (22.2%).
“As expected, the most common adverse event observed in the combination arms containing lenvatinib was hypertension. The most common adverse event in the combinations containing belzutifan was anemia,” Suarez Rodriguez said.
“In conclusion, observed efficacy of pembrolizumab plus lenvatinib were confirmatory of prior observations for this combination. Belzutifan/pembrolizumab plus lenvatinib and the anti-CTLA-4 combination had similar overall response rate compared to pembrolizumab/lenvatinib as first-line therapy in patients with previously untreated advanced clear cell renal cell carcinoma. Responses were potentially less favorable in the anti-LAG-3 and anti-TIGIT arms. Belzutifan plus pembrolizumab plus lenvatinib, but not the other investigative arms, may have been associated with a higher proportion of complete response, prolonged duration of response, and prolonged progression-free survival compared to pembrolizumab plus lenvatinib,” Suarez Rodriguez said in her concluding remarks.
Suarez Rodriguez also noted that belzutifan plus pembrolizumab plus lenvatinib and quavonlimab/pembrolizumab plus pembrolizumab are being evaluated in the phase 3 LITESPARK-012 study (NCT047367706).
DISCLOSURES: Suarez Rodriguez noted research funding and medical writing support from Merck Sharp & Dohme (MSD) LLC; research funding from Bristol Myers Squibb, Ipsen, Pfizer, and Roche; advisory board membership with Astellas, AstraZeneca, Bristol Myers Squibb, and MSD; travel accommodations from Bayer, speakers’ bureau membership with AstraZeneca, Astellas, Bristol Myers Squibb, Ipsen, and MSD; an invited speaker for Bristol Myers Squibb and MSD; and expert testimony for Bristol Myers Squibb and MSD.
Reference
1. Suarez Rodriguez C, Rojas CI, Shin SJ, et al. First-line pembrolizumab-based regimens for advanced clear cell renal cell carcinoma: KEYMAKER-U03 substudy 03A. Presented at: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract LBA96. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/LBA96.html.pdf
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Single Gene Swap Transfers Courtship Behavior Between Two Species For The First Time
Researchers have engineered a courtship ritual from one species of fruit fly into another using genetic modification.
A Japanese research team tweaked a single gene in the fly Drosophila melanogaster, causing it to display a courtship ritual…
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Lilah Fear/Lewis Gibson take spicy route to rhythm dance lead; Guillaume Cizeron finds “magic” on comeback
Cizeron not flawless but finds “magic” in comeback
France’s Guillaume Cizeron is no stranger to feeling victorious on Grand Prix de France ice, having won this Grand Prix stage a record six times with his former partner Gabriella…
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Lenvatinib/Everolimus Beats Cabozantinib in Phase 2 RCC Study
The combination of lenvatinib (Lenvima) and everolimus (Afinitor) reduced the risk of progression or death by 49% compared with cabozantinib (Cabometyx) for patients with metastatic clear cell renal cell carcinoma (ccRCC) following progression on a PD-1 inhibitor, according to findings from a phase 2 study presented at the
European Society for Medical Oncology Congress 2025 and simultaneously published in the Annals of Oncology.1,2In the multicenter phase 2 study, the median progression-free survival (PFS), which was the primary end point of the study, was 15.7 months with the combination of lenvatinib plus everolimus compared with 10.2 months with cabozantinib (HR, 0.51; 95% CI, 0.29-0.89; P = .02). There were more adverse events (AEs) observed with the combination, but these differences were not deemed statistically significant. Grade 3/4 AEs were experienced by 67.5% of those treated with lenvatinib plus everolimus compared with 50% of those receiving cabozantinib (odds ratio [OR], 2.08; 95% CI, 0.86-5.02).
“Lenvatinib plus everolimus significantly prolonged progression-free survival over cabozantinib,” Andrew W. Hahn, MD, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, said during a presentation of the results. “As the first head-to-head randomized comparison of contemporary second-line or later treatments after immune checkpoint inhibition, these results are relevant to treatment sequencing and inform oncology practice.”
The study enrolled 86 patients, with 40 receiving the combination and 46 receiving cabozantinib. For the combination arm, lenvatinib was administered at 18 mg per day and everolimus was given at 5 mg per day. Cabozantinib was administered at 60 mg per day. The most common prior treatment was the combination of nivolumab (Opdivo) and ipilimumab (Yervoy), which was received by 70.9% of patients enrolled in the study. This was followed by the combination of pembrolizumab (Keytruda) and axitinib (Inlyta) for 16.3%, adjuvant pembrolizumab for 4.7%, and any other checkpoint inhibitor for 8.1%.
Baseline characteristics were well balanced between the groups with most patients (69.8%) in each group having received 1 prior line of therapy and 30.2% having received 2 prior lines of therapy. Nearly half of patients had received prior VEGF-targeted therapy (45% for the combination arm and 41.3% for the single agent group). The IMDC risk was primarily intermediate in both groups (80% for combination and 73.9% for single agent). The IMDC risk was poor for 7.5% of those in the combination arm and for 8.7% of those in the control arm.
The objective response rate was 52.6% with lenvatinib plus everolimus compared with 38.6% with cabozantinib. Although numerically higher, this rate did not pass the bar for statistical significance (OR, 1.87; 95% CI, 0.75-4.6; P = .17). In addition to responses, stable disease was observed in 39.5% of those receiving the combination and for 54.5% of those in the single-agent arm.
The study was not designed to assess differences in overall survival (OS) and findings for this end point were still immature, Hahn noted. After a median of 20 months of follow-up, there had been 11 events in the combination arm and 13 in the control group. The 1-year OS probability was 87.0% with lenvatinib plus everolimus compared with 84.6% with cabozantinib (HR, 1.05; 95% CI, 0.47-2.38; P = .86).
Serious AEs were experienced by 27.5% of those treated with lenvatinib plus everolimus compared with 19.6% of those in the cabozantinib arm (OR, 1.56; 95% CI, 0.57-4.24). Dose interruptions were necessary for 70% of those in the combination arm compared with 78.3% of those in the cabozantinib group (OR, 0.65; 0.24-1.73). Dose reductions were necessary for 57% and 60.9% of those in the combination and control arm, respectively (OR, 0.80; 95% CI, 0.33-1.93). Treatment discontinuation was more common in the combination group at 20% compared with the single agent at 10.9% (OR, 2.05; 95% CI, 0.61-6.91).
“Of the 8 patients who discontinued treatment with lenvatinib plus everolimus, 5 of those were due to proteinuria,” said Hahn.
The most commonly observed AEs in the study aligned with those historically associated with each agent, Hahn noted. For the combination and single agent arms, respectively, the most common all-grade AEs were diarrhea (70% vs 73.9%), fatigue (72.5% vs 60.9%), proteinuria (65% vs 37%), hypertension (57.5% vs 39.1%), nausea (40% vs 39.1%), palmar-plantar erythrodysesthesia (20% vs 52.2%), vomiting (32.5% vs 34.8%), and oral mucositis (15% vs 43.5%).
“This is a positive phase 2 trial and demonstrates improved PFS and response compared with cabozantinib, but with higher toxicity,” said invited discussant Lisa M. Pickering, consultant medical oncologist at The Royal Marsden, MD, PhD, FRCP. “So, is it positive enough? I think that depends on you and your patient, but I would say that we can and should consider using lenvatinib/everolimus, particularly in patients for whom the priority is response and to who the toxicity rate is acceptable.”
The combination of lenvatinib and everolimus was approved by the FDA in 2016 for the treatment of patients with advanced RCC after a prior anti-angiogenic agent.3 The phase 2 study was completed to assess the combination in a more contemporary treatment setting, Hahn noted.
References
- Hahn AW, Chahoud J, Skelton W, et al. LenCabo: A randomized phase II multicenter trial of lenvatinib plus everolimus (len/eve) versus (vs) cabozantinib (cabo) in patients (pts) with metastatic clear cell RCC (ccRCC) that progressed on PD-1 immune checkpoint inhibition (ICI). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA94.
- Hahn AW, Chahoud J, Skelton WP, et al. A multicenter randomized phase II trial of lenvatinib plus everolimus versus cabozantinib in patients with metastatic clear cell RCC that progressed on PD-1 immune checkpoint inhibition (LenCabo). Ann Oncol. 2025. Doi:10.1016/j.annonc.2025.10.009.
- Lenvatinib in combination with Everolimus. FDA. May 16, 2016. Accessed October 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/lenvatinib-combination-everolimus
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AWS Introduces EC2 Instance Attestation
AWS has introduced EC2 instance attestation, a new security feature that enables customers to verify that their virtual machines are running approved software configurations in a cryptographically secure manner. The capability is powered…
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