The combination of pembrolizumab (Keytruda) plus concurrent chemoradiation therapy (cCRT) showed antitumor activity in patients with unresectable, locally advanced, stage III non–small cell lung cancer (NSCLC), regardless of PD-L1 status or tumor histology, according to follow up data presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer (WCLC) Singapore.

The phase 2 KEYNOTE-799 study (NCT03631784) enrolled a total of 216 patients with previously untreated, unresectable, pathologically confirmed stage IIIA–C NSCLC, with measurable disease per RECIST 1.1. Cohort A consisted of patients with both squamous and nonsquamous NSCLC, while cohort B included patients with nonsquamous NSCLC only.

All patients enrolled in the study received up to 17 cycles of pembrolizumab, administered at a dose of 200 mg, 3 times per week. Patients in cohort A also received physician’s choice of either paclitaxel or carboplatin 3 times per week on cycle 1, and either paclitaxel or carboplatin once weekly with thoracic radiotherapy on cycles 2 and 3.

Patients in cohort B followed the same dosing schedule for pembrolizumab, with the addition of pemetrexed or cisplatin on cycles 1-3 and thoracic radiotherapy during cycle 3.

The dual primary end points of the study were overall response rate (ORR), per RECIST v1.1, and the percentage of patients who developed grade 3 or higher pneumonitis.

A primary analysis of KEYNOTE-799, conducted after 15 weeks or more of follow up was presented during the 2020 ASCO Virtual Scientific Program and simultaneously published in the 

In this analysis, conducted after an additional 6 months of follow up, the ORR for cohort A (n = 112) was 69.6% (95% CI, 60.2-78.0), with 4 patients (3.6%) showing a complete response (CR). The median duration of response (DOR) for this patient population was not reached, however 82.2% of patients (n = 31) showed a DOR of 12 months or greater.

Response rates in cohort B (n = 61) were similar, with an ORR of 70.5% (95% CI, 57.4-81.5), including 3 patients (4.9%) who achieved a CR. Median DOR was not yet reached, though 72.1% (n = 5) of patients showed a DOR of 12 months or greater.

The median time to response was 2.1 months (range, 1.1-7.6) for cohort A and 2.2 months for cohort B (range, 1.8-10.3)

“Interestingly, in a substantial number of patients who had to discontinue treatment earlier, an ongoing control of the disease or an ongoing response was observed in some patients for a couple of months,” said Martin Reck, MD, PhD, of the Lung Clinic Grosshansdorf in Grosshansdorf, Germany, during an oral presentation of the data.

The 12-month progression-free survival (PFS) rate was 67.7% for cohort A, with a 12-month overall survival (OS) rate of 81.2%. Twelve-month PFS and 12-month OS for cohort B was 65.2% and 88.0%, respectively. Median PFS and median OS was not reached for either cohort.

Overall, 93.8% of patients in cohort A and 95.0% of patients in cohort B reported at least 1 treatment-related adverse event (TRAE). In total, 119 patients reported TRAEs of grades 3-5, with 54 patients discontinuing treatment due to AEs. Five patients experienced TRAEs that led to death.

Moreover, 17 patients experienced grade 3 or higher pneumonitis, though Reck noted that the majority of pneumonitis events were able to be resolved.

“The incidence of treatment-related events was within the established toxicity profiles of chemoradiotherapy and pembolizumab monotherapy,” said Reck.

Reck, M. Lee KH, Frost N, Kowalski DM, et al. Pembrolizumab plus platinum chemotherapy and radiotherapy in unresectable, locally advanced, stage III NSCLC: KEYNOTE-799. Presented at the the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer (WCLC) Singapore; January 28-31, 2021; Virtual. Abstract OA02.03.

Jabbour SK, Lee KH, Frost N, et al. Phase II study of pembrolizumab (pembro) plus platinum doublet chemotherapy and radiotherapy as first-line therapy for unresectable, locally advanced stage III NSCLC: KEYNOTE-799. 

. 2020;38(15 suppl):9008. doi: 10.1200/JCO.2020.38.15_suppl.9008

Articles

January 29, 2021 - The combination of pembrolizumab plus concurrent chemoradiation therapy showed antitumor activity in patients with unresectable, locally advanced, stage III non–small cell lung cancer, regardless of PD-L1 status or tumor histology.

Pembrolizumab Plus Chemoradiation Therapy Yields Promising Results for Patients with Unresectable, Locally Advanced NSCLC

Pembrolizumab (Keytruda) plus lanreotide (Somulatine Depot) elicited a stable disease (SD) rate of 39% in patients with advanced, progressive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to findings from the phase 1b/2 PLANET study that were presented at the 2021 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposium.

No new safety signals were identified in the study.

“Pembrolizumab has antitumor activity in a subset of GEP-NETs patients,” wrote the investigators. “We hypothesized that the lanreotide, by its antitumor effects and reduction of serotonin, a modulator of immunity, would synergize with pembrolizumab in low/intermediate grade GEP-NETs.”

In the phase 1b/2 PLANET study (NCT03043664), 22 GEP-NETs patients with a median of 2 prior systemic therapies (range 1-9) were treated with 90 mg of lanreotide and 200 mg of pembrolizumab every 3 weeks until disease progression or intolerable toxicity. A median of 6 doses of pembrolizumab (range 2-15) and 7 doses of lanreotide (range 2-15) were administered.

Median age at the time of enrollment was 60.9 years (range 51.1-82.0), 12 patients were male, 10 were female. To be eligible for the study, participants were required to meet the following criteria:

Non-resectable, recurrent, or metastatic well- or moderately-differentiated GEP-NETs with disease progression in the last 12 months

At least one measurable lesion based on RECIST 1.1

ECOG performance status of 0 or 1 and adequate organ function

Tumor mitotic rate of ≤20/10 hpf and/or Ki67 index ≤20%

Fourteen patients (63.6%) had tumors located within the gastrointestinal tract, of whom 8 patients (36.4%) had their primary tumor site located in the pancreas. Median time since diagnosis for all patients was 5.3 years, with 6 patients having received prior locoregional therapy and 3 patients receiving prior external beam therapy. Of the 12 tumors that were analyzed, 4 had detectable PD-L1 expression and 11 had tumor infiltrating lymphocytes.

The primary end point of the study was overall response rate (ORR), measured according to RECIST 1.1 criteria. Fifty-two percent of patients had progressive disease (PD). ORR, as measured by irRECIST to better assess the effect of immunotherapeutic agents, was 43% SD, 48% PD, with 9% of patients not evaluable.

Secondary end points were progression-free survival (PFS) and overall survival (OS). The median PFS was 5.4 months (95% CI, 1.7-8.3) and median OS at a median follow-up of 15 months was not reached.

Regarding safety, 6 of the 22 patients (27.3%) experienced treatment-related serious adverse events (AEs) including abdominal pain, pneumonitis, colitis, and hyperglycemia, which were all related to treatment with pembrolizumab. The most common treatment-related AE was hypothyroidism (23%), with other notable treatment-related AEs including colitis (9%), hyperglycemia (14%), and pneumonitis (5%). Three patients (13.6%) discontinued treatment due to AEs.

Investigators noted that peripheral blood immune analyses were pending and would be reported subsequently.

“Further studies to identify other approaches to increase the immunogenicity of well/moderately differentiated GEP-NETs are required,” concluded the investigators.

Morse M, Halperin DM, Uronis HE, et al. Phase Ib/II study of pembrolizumab with lanreotide depot for advanced, progressive gastroenteropancreatic neuroendocrine tumors (PLANET). Presented at: 2021 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. Abstract 369.

January 15, 2021 - Pembrolizumab plus lanreotide elicited a stable disease rate of 39% in patients with advanced, progressive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to findings from the phase 1b/2 PLANET study. 

Pembrolizumab/Lanreotide Combo Confers Antitumor Activity in GEP-NETs

The research, presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, showed that for patients with high cytogenetic risk, treatment with SVd led to an increase in overall response rate (ORR) and progression-free survival (PFS) despite a dosing schedule that utilized 40% less bortezomib and 25% less dexamethasone during the first 24 weeks of treatment.

“SVd is superior to Vd in patients with multiple myeloma, including high-risk disease, as supported by the progression-free survival in the different subgroups of patients with high-risk cytogenetics,” said Shambavi Richard, MD, of the Icahn School of Medicine at Mount Sinai. “Once weekly SVd is a highly active regimen, and may be an important treatment option for patients with high-risk multiple myeloma,” Richard added.

Of the 402 patients enrolled in the BOSTON study, 192 (48%) had high-risk (SVd, n = 97; Vd, n = 95) and 210 (52%) had standard-risk (SVd, n = 98; Vd, n = 112) cytogenetics. The SVd regimen demonstrated improved PFS relative to Vd in the high-risk (12.9 vs 8.1 months; HR, 0.67; 95% CI, 0.45-0.98; 

 = .0192) and standard-risk (16.6 vs 9.7 months; HR, 0.63; 95% CI, 0.42-0.95; 

 = .0131) groups. Moreover, ORR was significantly improved in the high-risk group (77.3% vs. 55.8%, respectively; 

For this post-hoc analyses, patients were deemed to be of high cytogenetic risk if they were found have at least of the following abnormalities in at least 10% of screened plasma cells:

The SVd regimen improved PFS in all high-risk subgroups except t(14;16), which was the smallest subgroup. Patients with a 17p deletion saw the greatest benefit, with a PFS of 12.22 months for those receiving the SVd regimen, vs 5.91 months for those treated with Vd. Patients with a 17p deletion also saw the greatest benefit in terms of ORR (76.2% vs 37.5%; 

The safety profiles of SVd and Vd in the high-risk and standard-risk groups were consistent with the overall study population. Of note, the rate of grade 2 or lower peripheral neuropathy was lower with SVd compared with Vd in both the high-risk (25.7% vs 35.7%, respectively; 

 = .100) and standard-risk groups (18.4% vs. 33.6%, respectively; 

“Despite recent advances in myeloma, high-risk anomalies such as deletion 17p, translocation 4;14 and translocation 4;16 are still associated with shorter progression-free survival and overall survival relative to those with standard-risk cytogenetic features,” noted Richard, adding “There’s an unmet need for novel therapies to improve outcomes of high-risk cytogenetics in myeloma patients. Selinexor’s novel mechanism [of] reactivating tumor suppressor proteins and reducing levels of oncoproteins may be particularly suited for high-risk disease.”

Richard, S. Once Weekly Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Twice Weekly Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory Multiple Myeloma: High Risk Cytogenetic Planned Subgroup Analyses from the Phase 3 BOSTON Study. Presented at: 62nd American Society for Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 1385.

December 5, 2020 - A subgroup analysis from the phase 3 BOSTON study demonstrated that once weekly selinexor, bortezomib, and dexamethasone was superior to bortezomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior therapies.

Weekly Selinexor Regimen Shows Significant Benefit in Pretreated Multiple Myeloma

Long-term follow-up of patients with locally advanced or metastatic urothelial carcinoma treated with enfortumab vedotin (Padcev) monotherapy showed encouraging results, with half of patients still alive at 12 months and approximately one-third alive at 18 months, according to data presented at the 2020 ESMO Virtual Congress.

Data from cohort 1 of EV-201 (NCT03219333), a single-arm phase 2 pivotal trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer previously treated with platinum-based chemotherapy and immune checkpoint inhibitors, demonstrated overall survival (OS) rates of 50.4% at 12 months and 34.2% at 18 months, respectively.

The study enrolled 125 patients, with a median age of 69 years and a median of 3 prior systemic treatments. The median follow-up for all patients was 22.3 months (0.5-27.3+), and median OS was 12.4 months (95% CI; 9.46-15.57). Patients received 1.25 mg/kg of enfortumab vedotin intravenously on days 1, 8, and 15 of a 28-day cycle. The median duration of treatment was 4.6 months, with a maximum duration of treatment of 27.3 months (ongoing as of data cutoff).

Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, which is highly expressed in urothelial carcinoma.

 The FDA previously granted accelerated approval to enfortumab vedotin based on data that demonstrated an overall response rate of 44%, which was the primary endpoint of EV-201.3 That data indicated that 12% of patients experienced complete response, and the median progression-free survival for patients receiving enfortumab vedotin was 5.8 months (95% CI, 4.9-7.5), with a median duration of response of 7.6 months (range, 0.95-11.30).

The most common treatment-related adverse events (AEs) included alopecia (49.6%), fatigue (49.6%), and decreased appetite (44%). The most common treatment-related AEs that were grade 3 or higher included neutropenia (8.0%), anemia (7.2%), and fatigue (6.4%). Twelve percent of patients discontinued treatment due to AEs, with peripheral sensory neuropathy (6%) being the most common. The investigators did report 1 treatment-related death from interstitial lung disease, confounded by high-dose corticosteroid use and suspected 

A confirmatory phase 3 trial, EV-301 (NCT03474107), has completed enrollment. That study will compare OS for patients with locally advanced or metastatic urothelial carcinoma treated with enfortumab vedotin with patients treated with chemotherapy.

1. O’Donnell MD, Galsky JE, Petrylak DP, et al. EV-201: Long-term results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial caner previously treated with platinum and PD-1/PD-L1 inhibitors. Poster presented at: ESMO Virtual Congress 2020; September 19-21, 2020. Abstract 746P.

2. Rosenberg J, Sridhar SS, Zhang J, et al. EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma. 

. 2020;38(10):1041-1049. doi:10.1200/JCO.19.02044

3. Kahl K. FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. 

. January 15, 2020. Accessed September 17, 2020. 

https://www.cancernetwork.com/view/fda-approves-first-agent-treat-locally-advanced-metastatic-urothelial-cancer

Long-term follow-up of patients with locally advanced or metastatic urothelial carcinoma treated with enfortumab vedotin monotherapy showed encouraging results, with half of patients still alive at 12 months and approximately one-third alive at 18 months.

Long-Term Follow-Up Shows Encouraging OS With Enfortumab Vedotin in Urothelial Carcinoma

Results from the phase III SPARTAN trial showed that apalutamide (Erleada) plus androgen deprivation therapy (ADT) significantly improved overall survival (OS) when compared with ADT plus placebo in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), according to findings presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program.

Apalutamide previously received FDA approval for the treatment of nmCRPC in February of 2018 following an interim analysis that showed significant improvement in metastasis-free survival (MFS).

“This final analysis of SPARTAN demonstrated that apalutamide significantly improved survival in men with nonmetastatic castration-resistant prostate cancer,” said lead author and presenter Eric J. Small, MD, of the University of California San Francisco Helen Diller Family Comprehensive Cancer Center. “And it did so despite a high rate of subsequent active therapy in the placebo group.”

At a follow up of 52.0 months, 428 of a required 427 OS events had occurred. Median OS for the apalutamide plus ADT group was 73.9 months vs 59.9 months for the ADT plus placebo (HR, 0.784; 

 = .0161). Apalutamide also significantly increased time to cytotoxic chemotherapy (HR, 0.629; 

 = .0002) when compared with the placebo arm.

The SPARTAN trial enrolled 1207 patients who were then randomized 2:1 to either apalutamide versus placebo, with a primary end point of MFS defined as the time from randomization to the first detection of distant metastasis on imaging or death. Primary analysis showed that treatment with apalutamide significantly improved metastasis-free survival (40.5 months vs 16.2 months, respectively) and time to symptomatic progression (HR, 0.45; 95% CI, 0.32-0.63; 

Following the release of those data, and at the recommendation of an independent data monitoring committee, the study was unblinded and all 76 eligible placebo patients crossed over to receive apalutamide.

The safety profile of apalutamide remained consistent with prior interim analyses even with substantially longer time of follow up, with 55.9% (n = 449) of patients reporting grade 3 or 4 treatment-related adverse events (AEs). Serious AEs were reported by 290 patients (36.1%), with 120 patients (14.9%) reporting AEs that lead to treatment discontinuation.

The most frequently reported AEs of any grade were fatigue (32.6%), hypertension (28.0%), and diarrhea (23.3%). Among grade 3 or 4 AEs, hypertension was most common (16.3%). Additional grade 3 or 4 AEs included skin rash (5.2%), fractures (4.9%), falls (2.7%) and ischemic heart disease (2.6%). The rates of these events did not change substantially after the first and second interim analyses.

Treatment discontinuation due to AEs was more common in apalutamide vs placebo, and 1 AE leading to death (resulting from myocardial infarction) was considered potentially related to apalutamide treatment.

Small EJ, Saad F, Chowdhury S, et al. Final survival results from SPARTAN, a phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC). Presented at: 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 5516.           

Smith Mr, Saad F, Chowdhury S, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. 

 2018; 378:1408-1418 DOI: 10.1056/NEJMoa1715546.

Results from the phase III SPARTAN trial showed that apalutamide plus androgen deprivation therapy significantly improved overall survival when compared with ADT plus placebo in patients with nonmetastatic castration-resistant prostate cancer. 

Apalutamide Plus ADT Leads to Significantly Improved Outcomes in Nonmetastatic CRPC

Treatment with pembrolizumab (Keytruda) induced a 4.9-month progression-free survival (PFS) benefit over brentuximab vedotin (BV) in patients with relapsed/refractory classical Hodgkin lymphoma, according to findings presented at the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.

"Pembrolizumab should be considered the preferred treatment option and the new standard of care in relapsed/refractory classical Hodgkin's lymphoma in patients that have relapsed post autologous stem cell transplant or are ineligible for autologous stem cell transplant," said lead author John Kuruvilla, MD, of the Princess Margaret Cancer Centre in Toronto, Canada.

Treatment with pembrolizumab showed an increase in PFS of 4.9 months (13.2 months vs 8.3 months; HR, 0.65; 95% CI, 0.48-0.88; 

 = 0.00271), and the benefit extended to several key subgroups, including those ineligible for autologous stem cell therapy (auto-SCT; HR, 0.61; 95% CI, 0.42-1.23), those with primary refractory disease (HR, 0.52; 95% CI, 0.33-0.83), and those who were BV-naïve (HR, 0.67; 95% CI, 0.49-0.92).

A total of 304 patients were enrolled in the randomized, open-label, phase III KEYNOTE-204 study, with 151 patients assigned to the pembrolizumab arm and 153 assigned to receive BV. All patients were aged ≥18 years and were either post auto-SCT or ineligible for auto-SCT. Both BV-naïve and BV-exposed patients were eligible for the study.

The primary end point of the study was PFS per blinded independent central review (BICR) per International Working Group criteria including clinical and imaging data after auto-SCT or allogeneic SCT along with overall survival.

The objective response rate was 65.6% for pembrolizumab vs 54.2% for the BV arm, with 24.5% of patients achieving a complete response and 41.1% of patients seeing a partial response to treatment with pembrolizumab. Duration of response also favored the pembrolizumab arm, with an increase of 6.9 months when compared with BV (20.7 months vs 13.8 months). Data cutoff for these results were January 16, 2020.

Safety reports were consistent with the known profiles of each agent. Serious treatment-related adverse events (TRAEs) were slightly higher for patients receiving pembrolizumab, with 16.2% (n = 24) reporting a serious TRAE.

The most commonly reported TRAEs were hypothyroidism (15.5%), pyrexia (12.8%), pruritis (10.8%), and fatigue (8.8%). Nineteen patients (12.8%) discontinued treatment due to TRAEs, compared with 25 (16.4%) in the BV arm. There was one death due to a TRAE with pembrolizumab, resulting from a grade 5 case of pneumonia.

Immune-mediated adverse events (IRAEs) were higher in the pembrolizumab arm, with the most common being hypothyroidism (18.9%) and pneumonitis (10.8%, of which 5.4% were grade 3/4 IRAEs). of the 16 patients who reported pneumonitis, 15 required treatment with corticosteroids, which led to resolution in 12 patients.

Kuruvilla J, Ramchandren R, Santoro A, et al. KEYNOTE-204: Randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL). Presented at: 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 8005

Treatment with pembrolizumab induced a 4.9-month progression-free survival benefit over brentuximab vedotin in patients with relapsed/refractory classical Hodgkin lymphoma.

Pembrolizumab Shows Superior PFS in Relapsed/Refractory Classical Hodgkin Lymphoma

Tivozanib (Fotivda) demonstrated a significant improvement in progression-free survival (PFS) compared with sorafenib (Nexavar), with similar overall survival (OS), in patients with highly relapsed.refractory metastatic renal cell carcinoma (RCC), according to results of the phase 3 TIVO-3 trial presented at the 2020 ASCO Virtual Scientific Program.

Results showed that the final hazard ratio (HR) for OS was 0.97 (95% CI, 0.75-1.24; 

 = .78). Moreover, an updated analysis of the data found that, with a median follow-up of 38 months for tivozanib and 40 months for sorafenib, the median OS was 16.4 months for tivozanib (95% CI, 13.4-22.2) and 19.2 months for sorafenib (95% CI, 15.0-24.2). A subset analysis showed the greatest benefit was derived by the cohort of patients who previously received a checkpoint inhibitor and VEGF inhibitor, with an HR of 0.55, or 2 VEGF TKIs, with an HR of 0.57.

Prior findings showed an increased median PFS for tivozanib when compared with sorafenib at 5.6 months versus 3.9 months, respectively (HR, 0.73; 95% CI, 0.56-0.94; 

“We believe the TIVO-3 data demonstrate a favorable risk/benefit profile for tivozanib in the growing population of patients who have relapsed or become refractory to multiple lines of therapy, including checkpoint inhibitors,” Sumanta Pal, MD, associate clinical professor, Department of Medical Oncology and Therapeutics Research, and co-director, Kidney Cancer Program, at City of Hope Comprehensive Cancer Center, said in a press release.

“The lack of clinical data to guide treatment decisions in a robust, evidence-based manner in this setting is a serious and growing unmet medical need, particularly as this population continues to grow thanks to improved treatment in earlier lines,” he added. “TIVO-3 provides the first positive superiority study to help guide this important treatment decision and, furthermore, offers this highly refractory patient population a favorable tolerability profile as indicated by fewer dose reductions, interruptions and discontinuations over a less selective VEGFR TKI in sorafenib.”

The TIVO-3 study was a controlled, multicenter, open-label, phase III trial which randomized 350 patients with highly refractory metastatic RCC who had failed ≥2 prior regimens, including VEGF-TKI treatment, 1:1 to receive either oral tivozanib or sorafenib. Crossover between arms was not permitted.

Eighteen percent (n = 31) of patients in the tivozanib arm achieved partial response, compared with 8% (n = 14) of those in the sorafenib arm. The objective response rate was 34% for tivozanib versus 24% for sorafenib.

Treatment with tivozanib was found to be generally well-tolerated, and the safety profile was favorable when compared with sorafenib. Treatment-related adverse events (TRAEs) were reported in 84% (n = 146) of patients receiving tivozanib and 94% (n = 160) of those receiving sorafenib. Serious TRAEs occurred in 11% (n = 19) of patients treated with tivozanib versus 10% (n = 17) of patients who received sorafenib.

The most common grade 3 or 4 AE reported in patients receiving tivozanib and sorafenib was hypertension (21% vs 14%, respectively). The most commonly reported any grade AEs associated with tivozanib were hypertension (38%), diarrhea (33%), fatigue (29%), and decreased appetite (27%).

The investigators reported significantly reduced dose reductions and interruptions due to AEs for tivozanib versus sorafenib (48% vs 63%; 

 = .0164), despite nearly double the average time of cycles initiated for the tivozanib arm (11.9 months vs 6.7 months, respectively). Treatment related AEs leading to permanent discontinuation were 8% for tivozanib compared with 15% for sorafenib.

Pal SK, Escudier B, Atkins MB, et al. TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). Presented at: 2020 ASCO Virtual Program; May 27, 2020. Abstract 5062           

AVEO Oncology Announces TIVO-3 Final Overall Survival Results Featured at ASCO 2020 Virtual Scientific Program and Submitted to U.S. FDA as Part of NDA Filing

 [press release]. Boston, Massachusetts. Published May 29, 2020. https://www.businesswire.com/news/home/20200529005120/en/. Accessed May 29, 2020.

Tivozanib demonstrated a significant improvement in progression-free survival when compared with sorafenib, with similar overall survival, in patients with highly relapsed or refractory metastatic renal cell carcinoma.

Kevin Wright