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Jeff Bezos and Lauren Sanchez know how to leave a mark with everything they do.

The couple made headlines with a lavish $50 million wedding in Venice, Italy attended by a long list of celebrities and media personalities including Leonardo Dicaprio, Orlando Bloom, Sydney Sweeney, Kim Kardashian, Oprah Winfrey, Tom Brady and many more.

Now the newly-wed couple is off to spend their honeymoon at a location that has immense value for the TV fans.

As reported by Independent, the pair is at San Domenico Palace, a Four Seasons hotel in Taormina, Sicily.

The venue is internationally recognized for its role as the ‘setting’ for HBO series The White Lotus season two.

The 61-year-old and the 55-year-old reached the Nicelli airport from Venice to take a helicopter ride back to the Amazon founder’s $500 million superyacht Koru.

The yacht is currently anchored in Taormina while the two are enjoying some quality time together.

For the unversed, while the wedding has drawn backlash from some people including Charlize Theron and Rosie O’Donnell, the bride had prepared hard for the wedding.

The licensed pilot had brought some lifestyle changes including dietary to lose a few pounds before walking down the aisle.

Additionally, she also got a piercing on the nail of her ring finger to take her glam look up a notch.

The nail artist Iram Shelton pierced a diamond-encrusted ‘B’ charm into the long nail.

Findings from a subgroup analysis of the phase 3 CheckMate 9DW trial (NCT04039607) demonstrated that the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) provided overall survival (OS) and overall response rate (ORR) benefits compared with lenvatinib (Lenvima) or sorafenib (Nexavar) in Chinese patients with unresectable or advanced hepatocellular carcinoma (HCC).1

Data presented at the 2025 ESMO Gastrointestinal Cancers Congress showed that at a median follow-up of 31.3 months (range, 15.4-46.5), Chinese patients treated with nivolumab plus ipilimumab (n = 98) achieved a median overall survival (OS) of 23.5 months (95% CI, 18.0-37.8) compared with 20.1 months (95% CI, 15.3-24.0) in those given lenvatinib or sorafenib (n = 110; HR, 0.82; 95% CI, 0.57-1.18). The 24-month OS rates were 48% and 39%, respectively.

In the Chinese subgroup, nivolumab plus ipilimumab elicited an ORR of 37% (95% CI, 27%-47%) compared with 14% (95% CI, 8%-22%) for lenvatinib or sorafenib (difference, 23.1%; 95% CI, 11.4%-34.3%). The rates of complete and partial response were 7% and 30%, respectively, in the experimental arm. These respective rates were 2% and 12% in the lenvatinib or sorafenib arm.

“The results further support nivolumab plus ipilimumab as a potential new first-line standard-of-care therapy for patients with unresectable HCC in China, a region with the highest HCC incidence and overall mortality rate from HCC globally,” lead study author Shukui Qin, MD, of Nanjing Tianyinshan Hospital of China Pharmaceutical University, and colleagues wrote in a poster presentation of the data.

In April 2025, the FDA approved nivolumab in combination with ipilimumab for the first-line treatment of adult patients with unresectable or metastatic HCC, based on data from CheckMate 9DW.²

CheckMate 9DW and Subgroup Analysis Overview

The randomized, open-label study enrolled patients with unresectable HCC who were naive to systemic therapy in the unresectable/advanced setting.1 Patients needed to have at least 1 measurable lesion per RECIST 1.1 criteria, a Child-Pugh score of 5 or 6, and ECOG performance status of 0 or 1, and no main portal vein invasion.

Patients were randomly assigned 1:1 to receive nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg once every 3 weeks for up to 4 cycles, followed by nivolumab alone at 480 mg once every 4 weeks (n = 335); or single-agent treatment with investigator’s choice of lenvatinib at 8 mg or 12 mg per day, or sorafenib at 400 mg twice per day. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal. Treatment in the experimental arm only lasted for a maximum of 2 years.

Stratification factors included etiology (hepatitis B [HBV] vs hepatitis C vs uninfected); macrovascular invasion (MVI) or extrahepatic spread (EHS; yes vs no); and alpha-fetoprotein level (<400 ng/mL vs ≥400 ng/mL).

OS served as the trial’s primary end point. Blinded independent central review (BICR)–assessed ORR and duration of response (DOR), along with time to symptom progression, were secondary end points. BICR-assessed progression-free survival (PFS) and safety were exploratory end points.

The subgroup analysis included 208 Chinese patients from mainland China (n = 29), Hong Kong (n = 67), Taiwan (n = 48), and an additional group from mainland China (n = 64).

Within the Chinese subgroup, the median age was 63.5 years (range, 37-84) in the nivolumab/ipilimumab arm vs 62 years (range, 26-81) in the control arm. The majority of patients were male (experimental arm, 80%; control arm, 81%), had an HVB etiology (79%; 70%), had a Child-Pugh score of 5 (76%; 79%), and had Barcelona Clinic Liver Cancer stage C disease (78%; 74%). An ECOG performance status of 1 was reported in 35% of patients and 13% of patients in the respective arms.

In the nivolumab/ipilimumab arm at baseline, 30% of patients had MVI, 52% had EHS, and 66% had both. These respective rates were 31%, 55%, and 72% in the control arm. Forty-two percent of patients in the experimental arm had an AFP level of at least 400 ng/mL compared with 39% of patients in the lenvatinib/sorafenib arm. The rates of prior local therapy were 43% and 58%, respectively.

Additional Subgroup Efficacy Data

The median DOR was not reached (95%% CI, 23.4-not evaluable [NE]) in the nivolumab/ipilimumab arm vs 8.4 months (95% CI, 6.4-NE) in the lenvatinib or sorafenib arm. The median time to response was 2.1 months (95% CI, 1.8-9.1) and 5.5 months (95% CI, 1.9-13.9), respectively.

Among evaluable patients, the median tumor reduction from baseline was –47.1% (interquartile range [IQR], –70.5% to –4.8%) in the nivolumab/ipilimumab arm (n = 77) vs –13.8% (IQR, –28.2 to 1.2) in the control arm. Any reduction was reported in 75% of patients in the experimental arm vs 72% of patients in the control group. In the nivolumab/ipilimumab arm, tumor reductions of more than 50% and more than 75% occurred in 45% and 21% of patients, respectively. These respective rates were 5% and 1% in the control arm.

Further analyses showed that the ORR benefit with nivolumab/ipilimumab was consistent across subgroups within the Chinese population.

Any subsequent therapy was administered to 47% of Chinese patients in the nivolumab/ipilimumab arm vs 55% of patients in the lenvatinib or sorafenib group. These included radiotherapy (experimental arm, 6%; control arm, 5%), surgery (4%; 3%), locoregional therapy (14%; 12%), and systemic therapy (41%; 52%). Types of subsequent systemic therapy included anti–PD-(L)1 therapy (5%; 15%), anti–PD-(L)1 plus anti–CTLA-4 therapy (0%; 3%), anti–PD-(L)1 plus anti-VEGF therapy (12%; 19%); platinum-based chemotherapy (1%; 0%), and anti-VEGF therapy (30%; 15%).

The median time to second progression (PFS2) was 22.0 months (95% CI, 15.7-34.0) in the experimental arm vs 15.5 months (95% CI, 13.1-18.6) in the control arm (HR, 0.76; 95% CI, 0.54-1.09).

QOL and Safety Findings

Numerical improvements in health-related quality of life were reported with nivolumab/ipilimumab over the course of the study, with the exception of week 25. In the experimental arm, mean changes from baseline in Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) surpassed the minimal important difference (MID) of 8 points between weeks 53 and 89; however, in the control arm, FACT-Hep score worsened at several time points, and the MID was exceeded at week 61.

Regarding safety, any-grade treatment-related adverse effects (TRAEs) occurred in 90% of patients in the nivolumab/ipilimumab arm vs 95% of patients treated with lenvatinib or sorafenib. The rates of grade 3/4 TRAEs were 43% and 38%, respectively. Serious TRAEs of any grade occurred at respective rates of 31% and 17%; the rates of grade 3/4 serious TRAEs were 27% and 15%, respectively. TRAEs led to treatment discontinuation in 20% of patients in the nivolumab/ipilimumab arm vs 13% of patients in the lenvatinib or sorafenib arm. TRAEs led to death in 3 patients (3%) and 1 patient (<1%), respectively.

In the nivolumab/ipilimumab group, hepatic TRAEs included hepatobiliary disorders (any-grade, 15%; grade 3/4, 12%), increased aspartate aminotransferase (AST) levels (23%; 1%) increased alanine aminotransferase (ALT) levels (18%; 3%), and increased bilirubin levels (11%; 0%). In this group, cardiac TRAEs and hemorrhagic TRAEs were reported at rates of 6% and 3%, respectively; no grade 3/4 cardiac or hemorrhagic TRAEs were noted.

In the control arm, hepatic TRAEs comprised hepatobiliary disorders (any-grade, 6%; grade 3/4, 3%), increased AST levels (16%; 0%) increased ALT levels (10%; <1%), and increased bilirubin levels (17%; 2%). The rates of any-grade cardiac TRAEs and hemorrhagic TRAEs were 51% and 12%, respectively; the respective rates of grade 3/4 cardiac and hemorrhagic TRAEs were 10% and <1%.

Immune-mediated AEs (irAEs) reported in the experimental arm included pneumonitis (5%), hepatitis (14%), rash (23%), hypothyroidism/thyroiditis (22%), hypothyroidism (13%), thyroiditis (10%), and hyperthyroidism (19%). irAEs that led to treatment discontinuation included pneumonitis (n = 1) and hepatitis (n = 2).

References

1. Qin S, Bai Y, Han G, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line (1L) treatment in Chinese patients with unresectable/advanced hepatocellular carcinoma (HCC): CheckMate 9DW expanded analyses. Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract 157P.
2. FDA approves nivolumab with ipilimumab for unresectable or metastatic hepatocellular carcinoma. FDA. April 11, 2025. Accessed July 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-hepatocellular-carcinoma