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A treatment combination of Imjudo (tremelimumab) and Imfinzi (durvalumab) demonstrated improved survival outcomes, including disease control and treatment responses in patients with unresectable (surgically unremovable) hepatocellular carcinoma (liver cancer), according to a presentation at the 

The presentation highlighted updated five-year data from the phase 3 HIMALAYA study. These results set new standards in unresectable liver cancer, with one in 5 patients alive at five years, Dr. Lorenza Rimassa said in the presentation. 

A combination treatment of Imjudo (tremelimumab) and Imfinzi (durvalumab) has shown improved survival outcomes in patients with unresectable liver cancer.

The phase 3 HIMALAYA study revealed that one in five patients treated with Imjudo plus Imfinzi were alive at five years, surpassing the 9.4% survival rate for those treated with Nexavar.

Patients in the Imjudo plus Imfinzi group experienced a median overall survival of 16.43 months compared to 13.77 months in the Nexavar group.

The Imjudo plus Imfinzi combination also demonstrated better disease control, with higher rates of complete and partial responses and lower rates of disease progression.

Rimassa is an associate professor of medical oncology at Humanitas University and head of the Hepatopancreatobiliary Oncology Department at Istituto di Ricovero e Cura a Carattere Scientifico Maugeri Humanitas Research Hospital in Milan, Italy.

“This five-year updated analysis of the HIMALAYA study presents the longest follow-up to date in phase 3 studies for [unresectable liver cancer],” Rimassa said. “[Imjudo plus Imfinzi] sustained an overall survival (OS; time patients live, regardless of disease status) benefit versus [Nexavar (Nexavar)] and demonstrated unprecedented long-term survival benefit at five years, with a five-year survival rate of 19.6% for [Imjudo plus Imfinzi] versus 9.4% for [Nexavar].”

Survival Benefits of Imjudo Plus Imfinzi Versus Nexavar in Unresectable Liver Cancer

A total of 1,171 patients were randomly assigned to three treatment groups. The Imjudo-Imfinzi combination group included 393 patients. There were 389 patients in the Imfinzi monotherapy group and patients 389 patients in the Nexavar group. In the study, 393 patients were treated with the Imjudo-Imfinzi combination and 389 patients received Nexavar.

Patients from the Imjudo-Imfinzi combination group compared with Nexavar sustained an OS benefit. Specifically, the median OS was 16.43 months in the combination group and 13.77 in the Nexavar group. The median follow-up duration was 62.49 versus 59.86 months, respectively.

For patients experiencing disease control, the OS was enhanced, showing rates of 28.7% in the Imjudo-Imfinzi combination group and 12.7% in the Nexavar group at five years and increasing over time. There were 12 patients (3.1%) in the Imjudo-Imfinzi combination group who achieved complete response (disappearance of cancer) versus no patients in the Nexavar group, and 67 patients (17.0%) experienced partial response (tumor shrinkage) versus 20 patients (5.1%), respectively. Stable disease was achieved by 157 (39.9%) in the Imjudo-Imfinzi combination group and 216 patients (55.5%) in the Nexavar group, and 141 patients (35.9%) versus 118 (30.3%), respectively, experienced disease progression.

“More patients treated with [Imjudo-Imfinzi combination] versus Nexavar were still alive, still on study treatment, and fewer received a subsequent therapy at five years,” Rimassa noted.

Patients receiving the Imjudo-Imfinzi combination also experienced deeper tumor responses, including over 50% shrinkage in 34 patients, which was associated with longer overall survival, compared with 12 patients receiving Nexavar. In addition, 80 patients in the Imjudo-Imfinzi combination group versus 114 patients in the Nexavar group experienced minor responses of less than 30% tumor shrinkage; however, this also led to a long-term survival benefit for those receiving Imjudo-Imfinzi combination. In the Imjudo-Imfinzi combination group, there were 168 patients who had no shrinkage or growth versus 169 patients in the Nexavar group.

Rimassa stated that there were no new serious treatment-related side effects after the primary analysis with a data cut-off on Aug. 27, 2023. At the five-year data cut-off of March 1, 2024, 17.5% of patients in the Imjudo-Imfinzi combination group had experienced serious treatment-related side effects, which was the same percentage reported at the primary analysis. Similarly, for the Nexavar group, at the five-year analysis at the data cut-off, there were 9.9% of patients who experienced serious treatment-related side effects versus 9.4% at the primary data cut-off.

There were also 24.8% of patients in the Imjudo-Imfinzi combination group that had serious non-treatment-related side effects at the five-year data cut-off versus 23% at the primary data cut-off, and in the Nexavar group, there were 20.3% of patients experiencing serious non- treatment-related side effects versus 20.3%, respectively.

“Overall survival benefit with [the Imjudo-Imfinzi combination] was enhanced in patients who achieved disease control. Any degree of tumor shrinkage was linked to long-term survival, with those experiencing deep responses showing the greatest benefit. These findings indicate that conventional response measures such as complete response or partial response … may not fully capture the benefits of [the Imjudo-Imfinzi combination],” Rimassa concluded.

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Articles

In patients with unresectable liver cancer, treatment with Imjudo plus Imfinzi showed better survival outcomes compared with Nexavar.

Imjudo Plus Imfinzi Improve Survival Versus Nexavar in Liver Cancer

Initial treatment with Lenvima (lenvatinib) continued to demonstrate higher success rates in patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC; no longer responding to treatment with radioiodine), according to real-world clinical data gathered from Europe and Canada presented at 

“We have included patients from different practice types, including community [17.6%] and academic [75.8%] settings, as well as different countries and regions, representing a highly heterogeneous population,” Dr. Laura Deborah Locati, said in a presentation of the data. Locati is associate professor in the Department of Medical Oncology at the University of Pavia and director of the Translational Oncology Unit at Istituto di Ricovero e Cura a Carattere Scientifico Maugeri in Milan, Italy.

Initial treatment with Lenvima continues to outperform other treatments for thyroid cancer, specifically radioiodine-refractory differentiated thyroid cancer.

The study relied on real-world clinical data from Europe and Canada, providing a more representative picture of Lenvima's effectiveness in a diverse patient population.

Patients treated with Lenvima experienced high progression-free survival rates at 12, 24 and 36 months, indicating that the disease was less likely to progress.

A significant number of patients achieved complete or partial responses to Lenvima treatment, demonstrating its effectiveness in controlling the disease.

In this study, real-world progression-free survival (PFS; the length of time during and after treatment when a patient with cancer lives with the disease without worsening) was measured from the beginning of Lenvima treatment until either the disease progressed or death occurred. If a patient experienced progression, PFS was not shown at the start of their next treatment or at the date of their last recorded activity. This applied to real-world overall survival (OS; the time from the start of treatment when a patient with cancer is still alive) rates as well.

The estimated PFS rates were 78.7% at 12 months, 61.5% at 24 months and 53.4% at 36 months. At 12 months the estimated OS rates were 92.2%, 83.1% at 24 months and 77.1% at 36 months. The median follow-up period was 17.9 months. At the end of the follow-up period, 79.8% patients were alive, 18.4% were deceased and 1.8% were reported as unknown.

Researchers established that 21.1% of patients experienced a complete response (the disappearance of all signs of cancer from treatment) and 53.7% had a partial response (a decrease in tumor size or extent of the disease in the body from treatment), resulting in an overall response rate (the percentage of patients with either a partial or complete response to treatment) of 74.8%. The estimated PFS rates at 24 months for those experiencing complete response was 95.5% and 57.3% had partial response. At 24 months the estimated OS rate was not reached for those who experienced complete response and 84.4% for those with partial response. Of note, when OS is not reached in a study, it means that at least half of patients were still alive at the time the data were analyzed. In addition, 21.4% of patients had stable disease (neither grows nor shrinks), 3.3% experienced disease progression and 0.6% were not recorded.

The median duration of treatment was 16.8 months and the median follow-up period was 17.9 months. Lenvima was administered once daily at a starting dose of 24 mg for 60.2% of patients, 20 mg for 24%, 18 mg for 12.2% and 14 mg for 3.6%.

“The main goal of this data collection was to assess the clinical effectiveness [of Lenvima] in real-world data from the patient population of radioiodine-refractory cases from different European countries, the UK and Canada,” Locati said.

In the phase 3, randomized, double-blind, multicenter SELECT trial, median PFS was longer in the Lenvima group at 18.3 months versus 3.6 months in the placebo group.

The response rate was 64.8% in the Lenvima group (including four complete and 165 partial responses) versus 1.5% in the placebo group. The median OS was not reached in either group.

Common treatment-related adverse effects in the Lenvima group included high blood pressure (67.8%), diarrhea (59.4%) and fatigue (59%). Lenvima led to discontinuation in 14.2% of patients versus 2.3% in the placebo group and six out of 20 deaths in the Lenvima group during the treatment period were drug related.

The retrospective patient chart review included 337 patients with RAI-R DTC who started first-line (initial treatment) Lenvima monotherapy on March 26, 2015, in Europe, or August 9, 2016, in Canada, until January 31, 2022. Lenvima was approved in Europe in 2015 and in Canada in 2016.

Regarding patient disease characteristics, 60.2% of patients had stage 3 or 4 disease with the following thyroid cancer types: follicular (51%), papillary (45.7%) and Hurthle cell (3.3%). In total, 98.8% of patients reported with metastases (the spreading of cancer) in various locations: 50.4% in the lymph nodes, 48.1% in the lung, 47.5% in the bone and 21.2% in the liver.

The majority (67.1%) of patients had an ECOG performance status score of 0 (meaning completing daily tasks entirely independently) or 1 (patients were able to complete most daily tasks independently) and 21.1% with 2 (patients were limited in activities) or greater. This was a key difference from the SELECT trial which did not include those with a performance status of 2 or greater, Locati noted. Other differences from the SELECT trial included specific criteria for RAI-refractory status, disease progression evidence and prior treatment with tyrosine kinase inhibitors, the researchers noted.

The study included patients from Canada (16.9%), France (16.3%), Germany (16.6%), Italy (17.8%), Spain (17.5%) and the United Kingdom (14.8%). Data was provided by 91 clinicians who are either medical or clinical oncologists (71.4%) or endocrine oncologists (22%).

“We recognize some limitations of this study: the lack of complete safety data, short follow-up period and real-world variation in clinical outcomes,” Locati concluded.

First-time treatment with Lenvima continues to outperform other treatments for thyroid cancer. 

Study Confirms Lenvima’s Benefits in Thyroid Cancer

Neoadjuvant (presurgical) Padcev (enfortumab vedotin) had promising treatment outcomes in patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC), according to updated findings from the EV-103 trial presented at the 2024 

American Society of Clinical Oncology Annual Meeting

“Importantly, from a safety standpoint, all patients in this trial who received neoadjuvant treatment proceeded to undergo cystectomy and there were no [Padcev]-related [side effects] that caused delay in surgery for any patients,” study author Dr. Peter H. O’Donnell said in a presentation of the data.

In a study of presurgical Padcev in 22 patients, the event-free survival rate was 62% at two years.

Eight patients (36.4%) achieved a pathological complete response, meaning that their disease was undetectable.

A total of 86.4% of patients successfully completed all three cycles of Padcev and the median duration of treatment was 2.1 months.

All patients were able to undergo surgery without delays due to Padcev-related side effects.

O’Donnell is an associate professor of medicine at the University of Chicago Medicine and specializes in genitourinary malignancies including prostate, kidney, testicular and bladder cancers.

In cohort H of the EV-103 phase 1b/2 study, Padcev was administered as a monotherapy treatment to 22 patients with MIBC who were cisplatin ineligible, meaning that they were not able to receive cisplatin chemotherapy treatments. The achieved event-free survival (EFS; time patients live without cancer signs and symptoms) rate was 62% at two years. In the overall population, however, the median EFS was not reached (NR), meaning that not enough patients experienced a cancer-related event for the researchers to calculate an average.

Of the evaluated patients, eight patients (36.4%) achieved a pathological complete response (pCR; disappearance of cancer) following neoadjuvant Padcev, and six patients remain disease-free at the data cut-off of Nov. 20, 2023, according to investigators. Also at the data cut-off, 15 patients continued long-term follow-up.

The median EFS for patients with a pCR was NR compared with patients without a pCR, which was 18.8 months.

Among patients, 86.4% successfully completed all three cycles of Padcev and the median duration of treatment was 2.1 months. The pCR rate was 36.4% and the pathological downstaging (pDS; decrease in the disease’s staging) rate reached 50%.

Patients included in the trial had either stage cT2 (tumor that grew into the muscular layer of the bladder wall; 68.2%), cT3 (cancer that has grown through the bladder wall into surrounding tissue; 27.3%) or cT4 (cancer that has grown extensively through the bladder wall into other organs; 4.5%) disease, 68.2% had urothelial carcinoma and 31.8% had a mixed histology. Of the patients evaluated (22 patients), the median age was 74.5 years. All patients were White (100%), 20 were male (90.9%) and 21 (95.5%) were current or former smokers.

Patients had an ECOG performance score of 2 or less, indicating that they could perform all or most of their daily tasks independently, and were eligible for surgical removal of the entire bladder and pelvic lymph node dissection.

Subsequent cancer-related therapy was administered to 36.4% of patients and included adjuvant therapy of Keytruda (pembrolizumab; two patients), carboplatin-based therapy (one patient), and Balversa (erdafitinib; one patient). One patient received systemic therapy for progressive disease, and three patients received other therapy.

The primary end point (main result measured at the end of a study) was pCR rate, and the secondary end points were pDS safety and EFS as determined by investigator assessment. This encompassed radiographic progression before radical cystectomy (RC), failure to undergo RC, gross residual disease at time of RC, recurrence or death.

“The safety profile for enfortumab vedotin was generally manageable and consistent with known prior [side effects] for this drug,” O’Donnell explained.

The prevalent treatment-emergent side effects associated with Padcev were fatigue (45.5%), changes in taste (36.4%) and hair loss (31.8%). There were 18.2% of patients who experienced moderate (grade 3) or greater Padcev-related side effects and the most common were dehydration, drug-induced skin disorder and high blood sugar (hyperglycemia) levels occurring in one patient each. Any-grade surgery-related side effects affected 68.2% of patients, with procedural pain (18.2%), anemia (13.6%) and constipation (13.6%) being the most common.

Most side effects were grade 1 or 2 (mild or serious) and those experiencing skin-related side effects and hyperglycemia side effects were resolved at 100%. Those experiencing peripheral neuropathy (pain or numbness in the hands and feet) were resolved at 44%.

There were three patients who died because of side effects not related to Padcev treatment, according to investigators. These deaths were acute kidney injury, cardiac arrest and pulmonary embolism, and each occurred less than 30 days after the last dose of Padcev.

Currently, there are no established neoadjuvant treatment options proven to enhance survival for patients diagnosed with MIBC who are ineligible for cisplatin and are undergoing radical cystectomy with pelvic lymph node dissection.

Padcev is an antibody-drug conjugate, which is a type of drug that binds to a target on immune cells and another on cancer cells, bringing the two together. The agent targets Nectin-4, a protein highly expressed in urothelial cancer. Both alone and in combination with Keytruda, Padcev improves overall survival (time patients live before death of any cause) compared with chemotherapy in patients with previously treated and untreated locally advanced or metastatic urothelial cancer.

“These follow-up data continue to show the efficacy of [Padcev] as a monotherapy treatment in the neoadjuvant setting for patients who are cisplatin-ineligible and have MIBC. These results also support the ongoing phase 2 and 3 trials that are evaluating [Padcev] alone and in combination with [Keytruda] for patients with MIBC,” O’Donnell concluded.

For patients with cisplatin-ineligible bladder cancer, presurgical Padcev decreased the cancer stage without leading to delays in surgery. 

Padcev Improves Outcomes for Cisplatin-Ineligible Bladder Cancer 

More than half of patients responded to treatment with Jakafi (ruxolitinib) plus Rezurock (belumosudil) to treat graft-versus-host disease (GVHD), according to data from a small study presented at the 2024 Tandem Meetings on Transplantation & Cellular Therapy.

“Response was observed with the combination despite progression on both agents as monotherapy, which may suggest synergistic effects in targeting different inflammatory pathways. The combination is tolerable, delays the need for alternative therapies, and facilitates the tapering of corticosteroids,” investigators wrote in the poster.

Among 20 patients observed in the study, the 55% overall response rate (ORR; percentage of patients who had a complete or partial response to treatment), included one (5%) complete response (CR; resolution of GVHD) and seven (35%) partial responses (PR) in patients at any time during the analysis.

Combination therapy with Jakafi and Rezurock showed promise in treating graft-versus-host disease, according to a small study.

Patients who did not respond to either Jakafi or Rezurock alone showed improved outcomes with the combination therapy, including complete or partial responses.

The majority of patients experienced a reduction in the need for other immunosuppressive agents after starting the combination therapy.

Side effects were generally manageable, although some patients developed pneumonia and upper respiratory infections.

Further large-scale studies are needed to fully assess the effectiveness, safety and long-term benefits of this combination therapy for GVHD.

However, one patient was excluded due to insufficient treatment time. There were three patients (15%) who experienced PR and then progression, six patients who had no response (30%), two patients who progressed (10%) and one patient who experienced a mixed response (5%).

The median time to response was 91 days, the duration of response was 48 days, and the median time to progression after a response was 28 days. Among the three patients who did not respond to Jakafi or Rezurock monotherapy, the combination therapy led to one patient showing a CR and two patients showing a PR.

There were five patients (25%) who discontinued treatment after a median of 125 days and all other immunosuppressive agents (drugs that impede the immune system to stop GVHD) were either decreased or discontinued in all patients that had a response to the combination.

According to response by organ system, there were seven organ types addressed: upper gastrointestinal (10% of patients had CR), liver (15% of patients had CR), lung (5% had CR, 15% each had either PR or progression), musculoskeletal (5% each had either PR or progression), ocular (5% each had either CR, PR, or progression), oral (10% each had either CR or progression and 15% had PR) and skin (5% each had either CR or PR).

Patients included in the analysis had previously undergone allogeneic hematopoietic cell transplantation, developed GVHD, and received the Jakafi and Rezurock combination between Feb. 1, 2022, and Aug. 30, 2023. Eligible patients could have any disease or transplant type and the effects of the combination therapy were monitored for up to 12 months from initiation.

The majority of patients were female (60%) with either myeloablative (65%) or reduced intensity (35%) conditioning regimens. Patients received either tacrolimus (Prograf) and methotrexate (MTX) (90%) or tacrolimus, MTX, and anti-thymocyte globulin (10%). The graft source received was either peripheral blood (95%) or bone marrow (5%) and the donor type was either matched but unrelated (75%) or related to the patient (25%).

The overall chronic GVHD (cGVHD) grade at diagnosis was either mild (45%), moderate (40%), or severe (15%), and the cGVHD at the onset of the combination was also mild (10%), moderate (25%), or severe (65%). For the best response cGVHD grade 10% of patients had mild best response, 30% had moderate, 55% had severe and 5% had CR.

Regarding side effects, there were no patients who had or developed cytomegalovirus (a common type of virus known as CMV), Epstein-Barr virus, graft failure or relapse disease, and there was no worsening of cytopenia.

However, four patients (20%) developed pneumonia and two developed (10%) an upper respiratory infection. Rezurock was decreased in one patient because of side effects not mentioned in the poster but then tolerated at the decreased dose, and one patient died while receiving the combination therapy.

Historically, Jakafi and Rezurock monotherapy has an ORR of 76%and 65%, respectively, according to prior studies published in 

. Other commonly used treatments have a lower response rate of 26%, as shown in the REACH3 study. Both Jakafi and Rezurock are well-tolerated medications with different primary targets: Jakafi targets the JAK/Stat pathway, whereas Rezurock targets ROCK2.

“Possible synergistic effects of combination therapy, targeting GVHD from multiple inflammatory pathways may yield higher response rates [and] possible underlying changes in the pathophysiology and manifestations of chronic GVHD over time, [which] could support re-introducing previously failed therapies for use in combination with other agents,” investigators hypothesized.

Moving forward, “large-scale studies [are] warranted to evaluate the efficacy, safety, and durability of response to combination therapy, though there may be overlapping downstream effects of STAT3 and STAT5,” they noted.

Jakafi plus Rezurock showed promise in treating graft-versus-host disease in patients who underwent undergone allogeneic hematopoietic cell transplantation. 

Morgan Bayer

Imjudo Plus Imfinzi Improve Survival Versus Nexavar in Liver Cancer

Study Confirms Lenvima’s Benefits in Thyroid Cancer

Padcev Improves Outcomes for Cisplatin-Ineligible Bladder Cancer

Drug Duo Is Efficacious in Treating Posttransplant GVHD

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