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Sanjay Popat, BSc, MBBS, FRCP, PhD, discusses OS data with amivantamab plus chemotherapy in EGFR-mutated, advanced NSCLC after progression on osimertinib.

Dr Popat on OS Outcomes With Amivantamab Plus Chemotherapy in EGFR-Mutated, Advanced NSCLC

Darolutamide plus ADT shows PFS benefit without docetaxel in metastatic hormone-sensitive prostate cancer.

Darolutamide Plus ADT Improves rPFS in mHSPC

Frontline abemaciclib plus ET demonstrated a superior ORR vs chemotherapy in HR+/HER2– advanced breast cancer with aggressive disease characteristics.

Abemaciclib/ET Combo Improves Responses vs Chemo in Aggressive HR+/HER2– Breast Cancer

Lutetium Lu 177 dotatate shows consistent efficacy over high-dose octreotide in advanced GEP-NETs, according to data from the NETTER-2 trial. 

Multivariate Analysis Provides Additional Insight on Efficacy of 177Lu-Dotatate in GEP-NETs

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Kristi Rosa joined MJH Life Sciences in 2016 and has since held several positions within the company. She helped launch the rapidly growing infectious disease news resource 

. Prior to working at the company, she served as lead copywriter and marketing coordinator at The Strand Theater. Email: krosa@onclive.com


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Tremelimumab plus durvalumab sustained an overall survival improvement in  unresectable hepatocellular carcinoma.

Durvalumab/Tremelimumab Sustains OS Benefit in Unresectable HCC

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Hernan Vargas, MD, FACS, a breast surgeon at Virginia Cancer Specialists, discusses the utility of sentinel lymph node biopsy in breast cancer.

Dr. Vargas on the Utility of Sentinel Node Biopsy in Breast Cancer

Brigatinib in NF2-Related Schwannomatosis with Progressive Tumors

Scott Plotkin, MD, reviews data from a phase II study on brigatinib, a multi tyrosine kinase inhibitor, across various tumor types in patients with NF2-related schwannomatosis.

Long-term Follow-up of Selinexor Maintenance for Patients With TP53wt Advanced or Recurrent Endometrial Cancer: A Prespecified Subgroup Analysis From the Phase 3 ENGOT-EN5/GOG-3055/SIENDO Study

David Miller, MD, reviews a plenary presentation (originally presented at the ASCO 2024 Annual Meeting by Vikky Makker, MD) on the long-term follow-up of the ENGOT-EN5/GOG-3055/SIENDO trial, focusing on selinexor maintenance for patients with TP53 wild-type advanced or recurrent endometrial cancer.

Clinical

Dr Rafiq on Novel Strategies for CAR T-Cell Engineering in Solid Tumors

Sarwish Rafiq, PhD, assistant professor, Department of Hematology and Medical Oncology, Emory University School of Medicine; program leader, CAR T Basic/Translational Research, Winship Center for Cancer Immunology, Winship Cancer Institute of Emory University, discusses how novel methods for engineering metabolically fit, memory rich CAR T-cells may address barriers to CAR T-cell efficacy in solid tumors.

At the Frontiers in Cancer Immunotherapy 2024 Symposium, Rafiq presented and shared 2 novel approaches to CAR T-cell engineering. The first multi-cytokine particle approach is a CAR T-cell extrinsic method, which involves engineering microparticles to enhance the manufacturing process of CAR T cells, Rafiq states. Since CAR T cells are extracted from patients, modified ex vivo, and then reinfused, this approach focuses on improving the quality of the cells during the manufacturing stage, she details. The engineered microparticles help in enriching the cells for memory phenotypes, which are associated with more durable responses in patients, Rafiq explains.

The second approach is a T-cell intrinsic method where CAR T cells are engineered to secrete their own antagonistic peptide against a novel immune checkpoint, Rafiq says. This modification alters the metabolism and activation profile of the CAR T cells, resulting in a more potent product, she describes.

Before these approaches can be used to manufacture CAR T cells for patients, additional GMP grade studies are needed, Rafiq continues. These studies will indicate whether the extrinsic approach can be implemented in a manufacturing facility to produce CAR T cells. For the intrinsic approach involving vasoactive intestinal peptide receptor antagonists, current research is focused on syngeneic mouse models, which involve the use of mouse CAR T cells in mice that have an intact immune system and tumors, Rafiq says. This research aims to determine if an endogenous immune response can be engaged and to assess any potential on-target off-tumor toxicities from antagonizing the receptor, she explains.

Additionally, studies addressing toxicity with the secreting CAR T cells are necessary to ensure their safety for patients, Rafiq notes. These steps are crucial for advancing these innovative CAR T-cell approaches from experimental stages to clinical application, she concludes.

Sarwish Rafiq, PhD, discusses how engineering metabolically fit, memory rich CAR T-cells may address barriers to CAR T-cell efficacy in solid tumors.

Perioperative chemotherapy with docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT protocol) led to a significant overall survival (OS) benefit vs neoadjuvant chemoradiation (CROSS protocol) in patients with resectable esophageal cancer

 according to findings from the phase 3 ESOPEC trial (NCT02509286) presented during the 

At a median follow-up of 55 months, patients in the intention-to-treat population who received the FLOT protocol (n = 221) achieved a median OS of 66 months (95% CI, 36-not evaluable [NE]) compared with 37 months (95% CI, 28-43) among those who were treated with the CROSS protocol (n = 217; HR, 0.70; 95% CI, 0.53-0.92; 

 = .012). The 3-year OS rates were 57.4% vs 50.7%, respectively, and the 5-year OS rates were 50.6% vs 38.7%, respectively.

Additionally, the median progression-free survival (PFS) was 38 months (95% CI, 21-NE) in the FLOT arm compared with 16 months (95% CI, 12-22) in the CROSS arm (HR, 0.66; 95% CI, 0.51-0.85; 

 = .001). The 3-year PFS rates were 51.6% vs 35.0%, respectively, and the 5-year PFS rates were 44.4% vs 30.9%, respectively.

“Many patients in the US and Europe are still treated with the CROSS radiochemotherapy protocol. Our study shows that patients with resectable esophageal cancer should have FLOT chemotherapy before and after the operation in order to optimize the chance of curing their tumors in the long term,” Jens Hoeppner, FAChirg, FACS, MD, the director of the Department of Surgery at University Medical Center, University of Bielefeld, in Detmold, Germany, stated in a press release.

ESOPEC was a prospective multicenter study that enrolled patients with esophageal adenocarcinoma across 25 sites in Germany between February 2016 and April 2020. Eligible patients needed to be at least 18 years old, have received no prior abdominal or thoracic radiotherapy, have an ECOG performance status of 2 or less, and have adequate organ function. Patients were also required to have pretreatment stage cT1N+, M0 or cT2-4a, N0/+, M0 disease. The presence of squamous or other non-adenocarcinoma histology, gastric cancer, clinical stage cT1cN0 and cT4b disease, or metastatic disease excluded patients from enrollment.

Patients were randomly assigned 1:1 to receive either the FLOT or CROSS protocol. Those in the FLOT arm received repeated doses of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel every 2 weeks over 4 neoadjuvant cycles prior to surgery and 4 adjuvant cycles after surgery. In the CROSS arm, patients received neoadjuvant radiation therapy and concurrent chemotherapy with carboplatin and paclitaxel for 5 cycles in 5 weeks prior to surgery. Following neoadjuvant treatment, patients in both arms waited 4 to 6 weeks before proceeding to surgery. 

The primary end point was OS. Secondary end points included PFS, recurrence-free survival, postoperative pathological stage, postoperative complications, and postsurgical quality of life.

At baseline, the mean age of patients in the FLOT and CROSS arms was 63.1 years (standard deviation [SD], 8.6) vs 62.6 years (SD, 9.8), respectively. Most patients in both arms were male (89.1% vs 89.4%), had clinical T-stage cT3-4 disease (79.1% vs 81.9%), and had clinical N-stage cN+ disease (77.8% vs 81.6%). Overall, 191 patients in the FLOT arm underwent surgery compared with 180 patients in the CROSS arm.

Additional findings from ESOPEC showed that the pathological complete remission rates among patients who underwent surgery in the FLOT arm was 16.8% compared with 10.0% in the CROSS arm. In both arms, complete regression (18.3% vs 13.3%) or near complete regression (25.1% vs 39.4%) was observed. Most patients across both arms underwent an R0 resection (94.2% vs 95.0%).

Patients in the predefined protocol population in the FLOT (n = 207) and CROSS (n = 196) arms achieved a median OS of 66 months (95% CI, 38-NE) vs 39 months (95% CI, 29-45), respectively (HR, 0.72; 95% CI, 0.54-0.96; 

 = .023). The 3-year OS rates were 58.1% vs 52.6%, respectively, and the 5-year OS rates were 51.8% vs 40.5%, respectively.

Results from an exploratory subgroup analysis demonstrated that the OS benefit in favor of FLOT vs CROSS was observed in all subgroups examined. The most pronounced benefit was reported in patients aged less than 60 years (HR, 0.57; 95% CI, 0.34-0.95) and those with clinical T-stage T3-4 disease (HR, 0.68; 95% CI, 0.50-0.92).

Most patients in both the FLOT and CROSS arms started neoadjuvant treatment; these patients comprised the predefined protocol population. A majority of patients in both arms completed neoadjuvant treatment (87.3% vs 67.7%) and received neoadjuvant treatment plus surgery (86.0% vs 82.9%). In the FLOT arm, 63.3% of patients received adjuvant treatment and 52.5% completed adjuvant treatment.

In the 90 days post-surgery, 3.2% of patients in the FLOT arm died compared with 5.6% in the CROSS arm. The 30-day postoperative mortality rates were 1.0% vs 1.7%, respectively At the data cutoff, 97 and 121 patients died in these respective arms.

“Perioperative chemotherapy with FLOT plus surgery improves OS compared with neoadjuvant chemoradiation with CROSS plus surgery in patients with locally advanced, resectable esophageal adenocarcinoma. ESOPEC found that perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with the CROSS protocol for improving survival in resectable esophageal adenocarcinoma,” Hoeppner concluded in an oral presentation. 

Hoeppner J, Brunner T, Lordick F, et al. Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial).

. 2024;42(suppl 17):LBA1. doi:10.1200/JCO.2024.42.17_suppl.LBA1

Chemotherapy before and after surgery may be new standard treatment for some patients with esophageal cancer. News Release. ASCO. June 2, 2024. Accessed June 2, 2024. https://society.asco.org/about-asco/press-center/news-releases/chemotherapy-and-after-surgery-may-be-new-standard-treatment

Perioperative chemotherapy compared to neoadjuvant chemoradiation in patients with adenocarcinoma of the esophagus (ESOPEC). ClinicalTrials.gov. Updated May 8, 2024. Accessed June 1, 2024. https://clinicaltrials.gov/study/NCT02509286

 study was published on June 2, 2024, from the press briefing, and was updated on June 4, 2024, with additional information/data from the oral session.

Perioperative chemotherapy using the FLOT protocol demonstrated a significant overall survival benefit over neoadjuvant chemoradiation (CROSS protocol) in patients with resectable esophageal cancer, as evidenced by the phase 3 ESOPEC trial. With a median follow-up of 55 months, the FLOT protocol achieved a median overall survival of 66 months compared to 37 months with the CROSS protocol. The study suggests that FLOT chemotherapy before and after surgery should be considered to optimize long-term tumor cure rates in these patients.

Perioperative chemotherapy with FLOT improved OS vs neoadjuvant chemoradiation with CROSS in resectable esophageal cancer.

Conference

Perioperative Chemotherapy Prolongs OS vs Neoadjuvant Chemoradiation in Esophageal Cancer

Neoadjuvant treatment with pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab, led to a statistically significant improvement in overall survival (OS) compared with neoadjuvant chemotherapy plus placebo, followed by adjuvant placebo, in patients with early-stage triple-negative breast cancer, according to data from the phase 3 KEYNOTE-522 trial (NCT03036488).

 showed that the perioperative pembrolizumab regimen reduced the risk of death by 34% compared with the placebo regimen (HR, 0.66; 95% CI, 0.50-0.87; 

 = .00150). At a median follow-up of 75.1 months, patients treated in the pembrolizumab arm (n = 784) achieved a 5-year OS of rate of 86.6% (95% CI, 84.0%-88.8%) vs 81.7% (95% CI, 77.5%-85.2%) for those in the placebo arm (n = 390). The OS event rates were 14.7% and 21.8% for the pembrolizumab and placebo arms, respectively.

“[KEYNOTE-522] was a positive trial for its 2 primary end points—short-term pathological complete response [(pCR) rate] and event-free survival [EFS]—and most importantly, [data] demonstrated that [the pembrolizumab regimen] reduced the risk of death by 34%,” lead study author Peter Schmid, MD, PhD, of Barts Cancer Institute at Queen Mary University in London, United Kingdom, said in a press briefing at the ESMO Congress.

Previously reported data from the first interim analysis of KEYNOTE-522 at a median follow-up of 15.5 months showed that patients in the pembrolizumab arm achieved a pathological complete response (pCR) rate of 64.8% (95% CI, 59.9%-69.5%) compared with 51.2% (95% CI, 44.1%-58.3%) those in the placebo arm (estimated difference, 13.6%; 95% CI, 5.4%-21.8%; 

Additionally, prior data from the fourth interim analysis demonstrated that the pembrolizumab regimen led to a significant improvement in event-free survival (EFS) vs the placebo regimen (HR, 0.63; 95% CI, 0.48-0.82; 

 < .001). The 36-month EFS rate was 84.5% (95% CI, 81.7%-86.9%) in the pembrolizumab group vs 76.8% (95% CI, 72.2%-80.7%) in the placebo group.

 in combination with chemotherapy as neoadjuvant treatment, then continued as a single agent as adjuvant treatment after surgery, for the treatment of patients with high-risk, early-stage TNBC based on prior data from KEYNOTE-522.

The randomized, double-blind trial enrolled patients at least 18 years of age with centrally confirmed TNBC in all foci. Patients needed to have newly diagnosed, previously untreated, nonmetastatic disease, defined as tumor stage T1c, nodal stage N1-2, or tumor stage T2-4, nodal stage N0-2. An ECOG performance status of 0 or 1 and adequate organ function. Notably, those with bilateral or multifocal primary tumors and inflammatory breast cancers were allowed to participate.

Patients were randomly assigned 2:1 to the pembrolizumab vs placebo arms. In the neoadjuvant setting, patients received pembrolizumab at 200 mg or placebo once every 3 weeks for 4 cycles plus paclitaxel at 80 mg/m2 once weekly plus carboplatin at area under the curve of 5 mg/mL per minute once every 3 weeks or 1.5 mg/mL per minute once weekly in the first 12 weeks. The second neoadjuvant treatment cycle consisted of pembrolizumab or placebo for 4 additional cycles plus doxorubicin at 60 mg/m2 or epirubicin at 90 mg/m2 plus cyclophosphamide at 600 mg/m2 once every 3 weeks for 12 weeks.

Those who completed or discontinued the first neoadjuvant cycle were allowed to start the second neoadjuvant cycle or undergo surgery. In the adjuvant setting, patients received pembrolizumab or placebo once every 3 weeks for up to 9 cycles. Radiation was also permitted in the adjuvant setting.

The trial’s dual primary end points were pCR rate and EFS in the intention-to-treat population. Secondary end points included pCR and EFS in patients with PD-L1–positive tumors, and OS among all patients and those with PD-L1–positive tumors.

Additional Efficacy Data Presented at ESMO

Updated efficacy analysis showed that the pembrolizumab regimen maintained a significant improvement in EFS vs the placebo regimen in the overall population (HR, 0.65; 95% CI, 0.51-0.83). The 5-year EFS rates were 81.2% for the pembrolizumab arm vs 72.2% for the placebo arm. EFS events were reported in 20.3% of patients in the experimental arm vs 29.2% of patients in the control arm.

Patients who achieved a pCR on the study also experienced an OS benefit, irrespective of treatment arm. For responders, the 5-year OS rate was 95.1% for the pembrolizumab arm (n = 495) vs 94.4% for the placebo arm (n = 217; HR, 0.69; 95% CI, 0.38-1.26). In non-responders, the 5-year OS rate was 71.8% for the pembrolizumab arm (n = 289) vs 65.7% for the placebo arm (n = 173; HR, 0.76; 95% CI, 0.56-1.05).

Schmid P, Cortes J, Dent R, et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: overall survival results from the phase III KEYNOTE-522 study. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA4.

Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. 

. 2020;382(9):810-821. doi:10.1056/NEJMoa1910549

Schmid P, Cortes J, Dent R, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. 

. 2022;386(6):556-567. doi:10.1056/NEJMoa2112651

FDA approves pembrolizumab for high-risk early-stage triple-negative breast cancer. FDA. July 26, 2021. Accessed September 15, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-high-risk-early-stage-triple-negative-breast-cancer

Neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab, improved overall survival in triple-negative breast cancer.

Neoadjuvant Pembrolizumab/Chemo, Adjuvant Pembrolizumab Boosts OS in Early TNBC

The addition of nivolumab (Opdivo) to tivozanib (Fotivda) did not improve clinical outcomes for patients with metastatic renal cell carcinoma (RCC) who experienced disease progression on or after therapy with a PD-(L)1 inhibitor, according to findings from the phase 3 TiNivo-2 study (NCT04987203).

“TiNivo-2 was the first phase 3 trial to evaluate the efficacy and safety of a PD-1 inhibitor following progression on or after treatment with a PD-[L]1 therapy,” Toni Choueiri, MD, of Dana-Farber Cancer Institute in Boston Massachusetts, said in a presentation of the data at the 

. “TiNivo-2 is a negative study, but I strongly believe it’s important. It is practice changing, and it should make us think twice now…These results support tivozanib monotherapy at 1.34 kg as a second-line therapy option in patients following progression on previous immune checkpoint inhibitor [ICI] therapy.”

At a median follow-up of 11.8 months in the tivozanib plus nivolumab arm (n = 171) and 12.5 months in the tivozanib monotherapy arm (n = 172), the median progression-free survival (PFS) was not improved with the doublet vs monotherapy (stratified HR, 1.10; 95% CI, 0.84-1.43; 

 = .49). Findings from the primary analysis of centrally reviewed PFS, which was the study’s primary end point, revealed that the median PFS was 5.7 months (95% CI, 4.0-7.4) for the combination vs 7.4 months (95% CI, 5.6-9.2) for tivozanib alone in the intention-to-treat population.

When examining centrally reviewed PFS by subgroups, no group appeared to benefit from the doublet vs monotherapy, according to Choueiri. The lowest HR was 0.92 (95% CI, 0.61-1.37) in patients 65 years of age or older, and the highest HR was 1.37 (95% CI, 0.69-2.73) in patients with International Metastatic RCC Database Consortium (IMDC) favorable-risk disease.

“This trial confirms and expands key conclusions from the [phase 3] CONTACT-03 study [NCT04338269]. [TiNivo-2] is the second phase 3 trial in RCC and solid tumors that suggests that ICI rechallenge should be generally discouraged regardless of treatment sequence. We [also] believe that the reduced dose of tivozanib in the combination arm may have impacted the efficacy, and that reflects in the lower median PFS [observed],” Choueiri said.

Diving Into TiNivo-2’s Design and Difference in Dosing Between Arms

Patients with locally advanced or metastatic clear cell RCC were enrolled following disease progression on 1 or 2 lines of therapy, 1 of which was an ICI they progressed on during or following at least 6 weeks of therapy. Patients needed to have an ECOG performance status of 0 or 1, measurable disease per RECIST 1.1 criteria, and a time from immediate prior line of therapy received to random assignment of 6 months or less.

“What remains unknown, in large part, is the optimal sequence [of therapies in RCC] in patients whose disease has progressed after treatment with an ICI. If we rechallenge with the same or a different ICI, does this improve clinical outcomes? Could outcomes be impacted if we use a non-ICI drug before ICI rechallenge and an ICI break? What about using a PD-1 vs PD-L1 inhibitor, does that matter?” Choueiri asked. He noted that following encouraging efficacy seen in the phase 1/2 TiNivo study (NCT03136627) with tivozanib plus nivolumab, TiNivo-2 was initiated.

Random assignment for TiNivo-2 was done in a 1:1 fashion, and stratification factors included IMDC risk category and prior therapy received (ICI as most recent therapy vs not). Patients in the tivozanib monotherapy arm received the agent orally at 1.34 mg on days 1 to 21 of each 28-day cycle. Those in the doublet arm received a reduced dose of 0.89 mg on the same schedule plus 480 mg of intravenous nivolumab given on day 1 of each cycle.

Choueiri noted that the reduced dose was agreed upon with regulatory authorities due to the potential risk of increased rates of grade 3/4 hypertension in the combination arm.

PFS by independent radiology review served as the trial’s primary end point, and secondary end points were overall survival (OS), PFS by investigator assessment, objective response rate (ORR), duration of response (DOR), and safety/tolerability.

Baseline patient characteristics were also well balanced between the two arms. The median age of patients in the tivozanib plus nivolumab arm was 64 years (range, 37-87) compared with 63 years (range, 33-82) in the tivozanib monotherapy arm. Most patients were male (73% for the combination vs 78% for tivozanib monotherapy), White (65% vs 62%), had an ECOG performance score of 1 (55% vs 51%), received 1 prior line of therapy (65% vs 61%), and received an ICI as their most recent therapy (71% vs 71%). Additionally, patients had favorable- (18% vs 18%), intermediate- (67% vs 66%), and poor- (16% vs 16%) risk disease by IMDC, and approximately one-third of patients did not receive a prior VEGFR-TKI (31% vs 31%).

When examining PFS by line of therapy, higher PFS rates were observed in the second-line setting, although tivozanib monotherapy bested tivozanib plus nivolumab. The median PFS among patients who received tivozanib plus nivolumab (n = 111) in the second-line setting was 7.3 months (95% CI, 5.4-9.3) vs 9.2 months (95% CI, 7.4-10.0) among patients treated with the monotherapy in this setting (n = 105; HR, 1.15; 95% CI, 0.82-1.62; 

Those who received treatment in TiNivo-2 as third-line therapy experienced a median PFS of 4.8 months (95% CI, 3.2-7.5) in the doublet arm (n = 60) vs 5.5 months (95% CI, 2.9-7.4) in the monotherapy arm (n = 67; HR, 0.97; 95% CI, 0.65-1.45; 

“I believe [these data] debunk the theory that break and rechallenge is better,” Choueiri added.

Furthermore, data revealed that the median OS was 17.7 months (95% CI, 15.1–not reached [NR]) in the tivozanib plus nivolumab arm compared with 22.1 months (95% CI, 15.2-NR) in the tivozanib monotherapy arm (HR, 1.00; 95% CI, 0.68-1.46; 

 = .9868). However, Choueiri noted that OS data were not mature; at data cutoff, 32% of events had occurred.

Additionally, the ORR was 19.3% (95% CI, 13.7%-26.0%) in the doublet arm vs 19.8% (95% CI, 14.1%-26.5%) in the singlet arm. One patient in each arm achieved a complete response. Patients also experienced stable disease (43.3% vs 47.1%), progressive disease (28.7% vs 25.0%), or were not evaluable (8.8% vs 8.1%). The median DOR was 15.77 months (95% CI, 5.65-NR) with the doublet compared with 9.66 months (95% CI, 3.71-NR) with monotherapy.

Safety Findings Are Comparable Between Arms

Adverse effects (AEs) leading to death occurred in 7 patients in the doublet arm and 5 patients in the tivozanib monotherapy arm. Patients experienced grade 2 or greater AEs (61% for the doublet vs 60% for the singlet), serious AEs (32% vs 37%), and treatment-emergent AEs leading to discontinuation (16% vs 19%), dose interruption (49% vs 54%), and dose reduction of tivozanib (11% vs 22%). The median duration of treatment was 6.3 months (range, 0.0-20.7) and 7.4 months (range, 0.1-17.9), respectively.

The most common any-grade AEs observed were hypertension (37% vs 40%), fatigue (29% vs 40%), diarrhea (30% vs 36%), and nausea (16% vs 28%), in the doublet and monotherapy arms, respectively.

Disclosures: Dr Choueiri cited receiving institutional and/or personal, paid and/or unpaid support for research, advisory boards, consultancy, and/or Honoria in the past 5 years, ongoing or not, from: Alkermes; Arcus Biosciences; AstraZeneca; Aravive; Aveo; Bayer; Bristol-Myers Squibb; Calithera; Circle Pharma; Deciphera Therapeutrics; Eisai; EMD Serono; Exelixis; GSK; Gilead; HiberCell; IQVIA; Infinity; Ipsen; Janssen Oncology; Kanaph Therapeutics; Lilly; Merck; NiKang Therapeutics; Neomorph; Neucon/Precede Biosciences; Novartis; OncoHost; Pfizer; Roche; Sanofi-Aventis; Scholar Rock; Surface Oncology; Takeda; Tempest Therapeutics; UpToDate; and CME events. He also cited having institutional patents filed on molecular alterations and immunotherapy response/toxicity and ctDNA. Choueiri also has equity in Tempest; Pionyr, Osel; Precede Biosciences; Curesponse; InnDura Therapeutics; and Premium. He is on committees for the NCCN; GU Steering Committee; ASCO; ESMO; ACCRU; and KidneyCAN.

Choueiri TK, Motzer RJ, Beckermann K, et al. Tivozanib–nivolumab vs tivozanib monotherapy in patients with renal cell carcinoma (RCC) following 1 or 2 prior therapies including an immune checkpoint inhibitor (ICI): Results of the phase III TiNivo-2 study. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA73.

The addition of nivolumab to tivozanib did not improve outcomes in metastatic RCC and 1.34 mg of tivozanib monotherapy may be considered as a second-line therapy. 

Hernan Vargas, MD, FACS

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