Rita Colorito

Pathologic complete responses (pCRs) were seen in 29% of patients with resectable hepatocellular carcinoma (HCC) treated with a perioperative immunotherapy regimen in the first interim analysis of a phase II trial, reported Yehia I. Abugabal, MD, in his presentation at the 2019 ILCA Annual Conference. The randomized, open-label study evaluated nivolumab (Opdivo) alone versus nivolumab plus ipilimumab (Yervoy) in patients with resectable HCC.

&ldquo;While surgical resection is associated with a very high recurrence rate, we currently do not have any effective neoadjuvant or adjuvant therapy despite the fact that hepatocellular carcinoma is a very immunogenic tumor. In fact, low intratumoral CD8 T cells and ratio Teff:Treg cells [effector T cells:regulatory T cells] has been shown repeatedly to be related to a high incidence of recurrence and low survival after hepatocellular carcinoma resection,&rdquo; said Abugabal, of The University of Texas MD Anderson Cancer Center in Houston. &ldquo;Recently, PD-1 antagonists have shown significant activity in hepatocellular carcinoma and have been granted conditional approval.&rdquo;

The study design was a randomized 1:1 trial of patients with resectable HCC, determined by surgeons as good candidates for either conservative hepatic resection or liver resection with curative intent. Thirty patients were expected to be enrolled and randomized between arms A and B. The primary endpoints were safety and tolerability, and the secondary endpoints included overall response rate and time until recurrence. Additional exploratory objectives focused on immunological/biomarker changes in the tumor tissue and peripheral blood.

Arm A received neoadjuvant nivolumab alone at 240 mg intravenously (IV) every 2 weeks for three doses. Surgery took place at the 6-week mark, followed by adjuvant nivolumab starting at week 10 at 240 mg IV every 2 weeks until recurrence or up to 2 years. Surveillance, including imaging, blood samples, insulin-like growth factor-1 score, and magnetic resonance elastography, occurred every 12 weeks.

Arm B followed the same surgical timeline, but with a neoadjuvant combination therapy of nivolumab 240 mg IV plus ipilimumab 1 mg/kg IV every 2 weeks for 3 doses. Adjuvant chemotherapy included nivolumab alone at 240 mg IV every 2 weeks plus ipilimumab 1 mg/kg IV every 6 weeks for up to 2 years or until recurrence, with surveillance completed every 12 weeks.

Four patients achieved a pCR, with a 50/50 split between the 2 study arms. One patient in each arm who achieved pCR had hepatitis C virus (HCV), one patient in the nivolumab-alone arm had hepatitis B virus (HBV), and one patient in the combination arm did not have hepatitis.

Two patients in arm A experienced grade 3 or higher treatment-related adverse events (TRAEs) post-operatively, including possible lipase and amylase increases. In arm B, 2 patients experienced grade 3 or higher events prior to surgery, of possible increases in ALT/AST, and one patient had a grade 3 TRAE post-operatively of definite colitis.

Treatment was deemed safe and surgical resection was not delayed. Only 1 patient did not undergo planned resection due to reasons that were unrelated to the study treatment.

Blood sampling and tumor sampling also took place prior to treatment as well as prior to surgery. &ldquo;Imaging showed that prior to surgery the tumor looked very vascular, typical of HCC. At the time of surgery, there was no enhancement in the tumor,&rdquo; said Abugabal.

&ldquo;Further analysis identified very specific highly cytotoxic tumors in CD8 T cells,&rdquo; he said. &ldquo;These are a reflection of the activity of cytotoxic T cells.&rdquo;

Pathological complete response was associated with a significant increase in 2 specific clusters of CD8 T cell and in the Teff/Treg ratio after therapy.

Two more patients have since been enrolled in the study, Abugabal noted.

&ldquo;After validation, the study may contribute to a paradigm shift in the perioperative treatment of resectable HCC,&rdquo; he concluded.

Kaseb AO, Duda DG, Tran Cao HS, et al. Randomized, open-label, perioperative phase II study evaluating nivolumab alone versus nivolumab plus ipilimumab in patients with resectable HCC. Presented at: 2019 ILCA Annual Conference; September 20-22, 2019; Chicago, IL. Abstract O-02.

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Pathologic complete responses were seen in 29% of patients with resectable hepatocellular carcinoma treated with a perioperative immunotherapy regimen in the first interim analysis of a phase II trial, reported Yehia I. Abugabal, MD, in his presentation at the 2019 ILCA Annual Conference.

Perioperative Nivolumab/Ipilimumab Combo Showing Early Promising Results in HCC

Clinically meaningful and durable objective responses were observed in the phase Ib (GO30140) subgroup efficacy analysis of atezolizumab (Tecentriq) plus bevacizumab (Avastin) in patients with previously untreated, unresectable hepatocellular carcinoma (HCC). In his presentation at the 13th Annual Conference of the International Liver Cancer Association in Chicago, investigator Kyung-Hun Lee, MD, said the combination of 2 anti-VEGF monoclonal antibodies may provide patients with unresectable HCC with a new treatment option that was well tolerated with manageable toxicities.

Approximately 80% of patients with HCC present with unresectable cancer requiring other therapies. VEGFR tyrosine kinase inhibitors are the first-line systemic standard of care for patients with unresectable or metastatic HCC. These are associated with modest survival benefits but considerable toxicities. A phase III non-inferiority trial put unconfirmed overall response rates per RECIST 1.1 at 19% for lenvatinib (Lenvima) and 7% for sorafenib (Nexavar).

In randomized studies, single-agent PD-L1/PD-1 immune checkpoint inhibitors have shown clinical activity against HCC, but not superiority over standards of care, noted Lee, of the department of Hemato Oncology, Medical Oncology Center, Seoul National University Hospital, South Korea.

&ldquo;Many HCC tumors are hypervascularised and overexpress VEGF and PD-L1, and we know that the anti-VEGF monoclonal antibody bevacizumab has shown modest single-agent activity in HCC,&rdquo; said Lee. &ldquo;In addition to anti-angiogenic activity, bevacizumab also showed immunomodulatory effects. We also know that PD-L1 with VEGF has shown clinical benefit in other tumor types.&rdquo;

The study design of the phase Ib trial focused on various tumor types, including gastric, pancreatic and esophageal cancers, with measurable disease per independent review facility (IRF)assessed RECIST 1.1 criteria, and EGOG performance status of 0 or 1, and adequate hematologic and organ function. Patients with prior systemic therapy were excluded.

Arm A, the HCC study arm, enrolled 104 patients with unresectable HCC with a Child-Pugh score up to B7. Patients were given atezolizumab 1200 mg IV every 3 weeks plus bevacizumab 15 mg/kg IV every 3 weeks.

The primary endpoints in arm A were treatment safety and IRF-assessed object response rate (ORR) per RECIST 1.1. Key secondary endpoints also include duration of response (DOR) and progression-free survival (PFS) per IRF RECIST, ORR, DOR and PFS per IRF HCC modified RECIST criteria (HCC mRECIST). Lee said data on some key secondary endpoints will be available at upcoming conferences.

The majority of patients enrolled were male (81%) with a median age of 62, with 57% from Asia, excluding Japan. Forty-nine percent of patients had hepatitis B (HBV) and 30% had hepatitis C (HCV). Extrahepatic spread (EHS) or macrovascular invasion (MVI) was present in 88% of patients.

In the study arm, 36%of patients had confirmed ORR, with 12% of patients achieving complete response. &ldquo;We had duration response with this study, ranging from 1.6 months to 31 months. More than half of the patients (54%) enjoyed a duration of response of more than nine months,&rdquo; said Lee, adding that DOR was consistent across analyses: HCC mRECIST (61% of patients) and investigator (INV)-assessed RECIST (62%). In addition, 76% of responses per IRF-assessed RECIST 1.1 are ongoing and the median duration of response was not reached, noted Lee.

The combination of atezolizumab and bevacizumab resulted in a median PFS also consistent across the 3 analyses: Both RECIST and HCC mRECIST showed 66% of patients with a median PFS of 7.3 months. INV RECIST showed 72% of patients with a median PFS of 7.4 months. Median overall survival, measured by HCC mRECIST, was 17.1 months, with a 6-month overall survival rate of 82% and a 12-month OS of 63%. &nbsp;&nbsp;

&ldquo;The benefits of atezolizumab and bevacizumab was generally consistent among patient subgroups, with clinical activity observed irrespective of PD-L1 status,&rdquo; said Lee.

Median treatment duration was 8.3 months on atezolizumab and 8.2 months on bevacizumab. Eighty-eight percent of patients experienced any grade treatment-related adverse events (TRAEs), with 39% having grade 3/4 treatment-related AEs and 3% grade 5. The most common AEs were proteinuria (37%), decreased appetite (35%) and fatigue (28%). The most common Grade 3/4 AE was hypertension, noted Lee, with 14% of patients experiencing it. In addition, 24% of patients had serious treatment-related AEs, including pyrexia (5%), cholangitis (3%), and upper gastrointestinal hemorrhage (3%).

The most common adverse event of special interest (AESIs) related to atezolizumab was rash (23%) and to bevacizumab was proteinuria (37%). Grade 3-4 bleeding AESIs associated with bevacizumab included 2% of patients with upper gastrointestinal bleeding and 2% of patients with esophageal varices hemorrhage.

&ldquo;Fifteen patients (14%) required systemic corticosteroids within 30 days of experiencing an adverse event on atezolizumab,&rdquo; said Lee. Increased AST and ALT levels (3% of patients each) were the most common hepatic events requiring systemic steroids within 30 days of an AE. No new safety signals were identified beyond the established single-agent safety profiles, said Lee.

&ldquo;In conclusion, this combination of atezolizumab and bevacizumab may become a promising treatment option for patients with unresectable HCC,&rdquo; said Lee. This combination is being evaluated further in the IMbrave150 phase III study (NCT03434379).

Lee KH, Ryoo BY, Hsu C-H, et al. Phase IB study results: safety and efficacy of atezolizumab + bevacizumab versus atezolizumab in patients with previously untreated, unresectable, or advanced hepatocellular carcinoma. Presented at: 13th Annual Conferences of the International Liver Cancer Association; September 20-22, 2019; Chicago, IL. Abstract 0-32.

Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial.

. 2018;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

Clinically meaningful and durable objective responses were observed in the phase Ib subgroup efficacy analysis of atezolizumab plus bevacizumab in patients with previously untreated, unresectable hepatocellular carcinoma.

Atezolizumab Plus Bevacizumab Offers a Promising Option for Unresectable HCC

The final analysis of KEYNOTE-240 (NCT02702401), a phase III study of pembrolizumab (Keytruda) in advanced hepatocellular cancer (HCC), demonstrated favorable benefit in overall survival (OS) and progression-free survival (PFS), according to Richard S. Finn, MD, during his presentation at the 13th Annual Conference of the International Liver Cancer Association in Chicago.

Sometimes not reaching prespecified statistical significance isn&rsquo;t the end of the line for second-line therapies for advanced HCC. Clinical significance should be considered when it comes to the results of the KEYNOTE-240 study for this patient population, Finn argued.

OS was higher in the pembrolizumab arm, at 13.9 months versus 10.6 months on placebo (HR, 0.781; 95% CI, 0.611-0.998;

= 0.0238). In both the primary and final analysis, PFS in the pembrolizumab arm was only slightly longer than placebo, 3 months versus 2.8 months. Both had favorable HRs of less than 1. The primary analysis had a HR of 0.775 and a

-value of 0.0186 (95% CI, 0.609-0.987). The final analysis had a HR of 0.718 and a

value of 0.0022 (95% CI, 0.570-0.904), again barely missing the efficacy endpoint of 0.0020, noted Finn.

The positive data generated over the last 2 years has seen new agents in liver cancer. Lenvatinib (Lenvima) has been added as a frontline therapy, as well as several agents in the second lines, including regorafenib (Stivarga), cabozantinib (Cabometyx), and the monoclonal antibody ramucirumab (Cyramza).

&ldquo;However, still this is an incurable disease and we know that HCC does develop into an inflammatory milieu and therefore it&rsquo;s been of interest to use drugs that target the immune system,&rdquo; said Finn, assistant professor of medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles. Early phase II studies have demonstrated encouraging antitumor activity and manageable safety, including the CheckMate-040 (NCT01658878) study of nivolumab and the KEYNOTE-224 (NCT02702414) study of pembrolizumab. Both of these therapies have now reached accelerated approval as a result of these data sets in the United States.

&ldquo;KEYNOTE-240 was the definitive study to show that pembrolizumab would improve survival versus best supportive care (BCS) in the second-line population. Arguably this is the last placebo-controlled phase III study in the second-line that we&rsquo;ll see,&rdquo; said Finn.

As with other second-line studies, the design of the trial focused on patients who had a progression or intolerance on first-line therapy sorafenib. Patients with main portal vein invasion were excluded. A study population of 413 patients was randomized 2:1, with patients in the pembrolizumab arm getting 200 mg every 3 weeks plus BCS and the other group getting saline-placebo every three weeks plus BCS.

The study had dual primary endpoints: OS and PFS assessed using conventional RECIST v1.1 criteria. &ldquo;It&rsquo;s very important we understand the statistical analysis for this study,&rdquo; noted Finn. &ldquo;There were dual endpoints and therefore the alpha (&alpha;) was split.&rdquo; Starting with a Type 1 error of (&alpha;)=0.025 that was then allocated between progression-free survival, where PFS &alpha;=0.002 and overall survival, where OS &alpha;=0.023.

&ldquo;Over the course of the study there were a number of interim analyses which required the OS &alpha; to be redistributed,&rdquo; said Finn. Therefore, to be considered positive at the end of the study, efficacy boundaries were set at

The pembrolizumab arm had 278 randomized patients, and the placebo arm had 135. At the time of Finn&rsquo;s analysis, 5 patients completed and 28 patients were still being treated on the pembrolizumab arm, versus 1 patient completing treatment and 4 ongoing on the placebo arm. For both arms, the majority of patients, 245 in pembrolizumab and 130 in placebo, discontinued treatment, most due to progressive disease, 173 and 100 patients, respectively.

Overall, 40% of patients came from the EU and North America and 40% came from Asia and Japan, well-balanced in both arms. Twenty percent of patients had Barcelona Clinic Liver Cancer B stage, 80% had C. In addition, 40% had viral hepatitis as an etiology, and of those, a majority had hepatitis B (25.9% in pembrolizumab and 21.5% in the placebo arm).

Prior sorafenib use was similar across both arms, with discontinuation due to intolerance at approximately 13% and discontinuation due to progressive disease at approximately 87%. Duration of sorafenib was approximately 5 months and time from stopping sorafenib to starting KEYNOTE-240 was a little over a month, similar for both arms. Macrovascular invasion was 12.9 in the pembrolizumab arm. &ldquo;That&rsquo;s lower than we&rsquo;ve seen in other phase III studies in the second-line,&rdquo; noted Finn.

The objective response rate (ORR) at final analysis was encouraging, said Finn. A total of 18.3% patients in the pembrolizumab arm had a partial or complete response (2.2%) with the median duration lasting 13.8 months, compared to placebo with only 4.4% of patients showing only a partial response with no duration of response reached.

&ldquo;Pembrolizumab, essentially, has shifted the number of patients who are non-responders to responders and also decreased the number of patients who had progressive disease,&rdquo; said Finn.

The adverse events related to pembrolizumab were not surprising, said Finn though the number of Grade 3/4 events were increased. The number of immune-mediated adverse events (IMAEs) were also higher in the pembrolizumab patients, at 18.3% versus 8.2% versus placebo. However, the number that led to discontinuation of treatment for IMAEs was only 3.6%, meaning that IMAEs are something that can be managed, said Finn.

The most common adverse events regardless of etiology were an increase in AST (22.6%), bilirubin (18.6%), fatigue (18.6%), and pruritus (18.3%). There was also a frequency of these adverse events that occurs with placebo. The most common pembrolizumab treatment-related adverse events were mostly low grade events of pruritus (13.3%), fatigue(10%), diarrhea (8.2%) and rash (8.2%). A greater percentage of AST increase were Grade 3/4 (5.4%).

Immune-mediated events were increased with pembrolizumab but there were no new immune-mediated events compared to other tumor types, said Finn. &ldquo;These were generally dominated by hypo- and hyperthyroidism.&rdquo;

&ldquo;Using 3 different analyses of post-treatment impact on OS, we&rsquo;re seeing hazard ratios in the 0.6 range. This is closer to what was anticipated in the study design when taking into account subsequent treatments,&rdquo; said Finn.

In summing up the phase III study, Finn noted: Pembrolizumab reduced the risk of death by 22%, with a hazard ratio of 0.78. It also improved PFS over placebo in patients with advanced HCC. However, these P-values did not reach statistical significance as outlined by the study. The response rate was higher with pembrolizumab, confirming the findings of phase II study. The safety profile wasn&rsquo;t different for this class of drug across other tumor types.

&ldquo;The benefit here, we would say, as captured by the OS and PFS response rate is favorable, and, I would argue supports the FDA approval for pembrolizumab in the second-line settings based on accelerated approval mechanisms,&rdquo; said Finn. In the meantime, he&rsquo;s awaiting the results of an ongoing phase III study from China, the KEYNOTE-3994 in the Asian Pacific region.

Finn also shared previously unpublished data on biomarkers. While the KEYNOTE-40 trial didn't require tissue sample, PDL-staining was performed on 76 patients in the pembrolizumab arm. Combined positive (CPS) and tumor proportion (TPS) were not significantly associated with clinical response to pembrolizumab, contradicting previously observed data in KEYNOTE-224 that found a clinical response association. Finn urged extreme caution in interpreting the results, as the number of patients studied was small.

Finn DS, Ryoo BY, Merle P, et al. Results of a phase 3 study of pembrolizumab versus best supportive care for second-line therapy in advanced hepatocellular carcinoma: KEYNOTE-240. Presented at: 13th Annual Conferences of the International Liver Cancer Association; September 20-22, 2019; Chicago, IL. Abstract O-01.

The final analysis of KEYNOTE-240, a phase III study of pembrolizumab in advanced hepatocellular cancer, demonstrated favorable benefit in overall survival and progression-free survival, according to Richard S. Finn, MD, during his presentation at the 13th Annual Conference of the International Liver Cancer Association in Chicago.

Second-Line Pembrolizumab Confers Improved OS, PFS in Patients With Advanced HCC

Patients with advanced hepatocellular carcinoma (HCC) treated with cabozantinib (Cabometyx) had higher alpha-fetoprotein (AFP) response rates versus those treated with placebo, according to findings of a subanalysis of the phase III CELESTIAL trial. In presenting these findings at the 13th Annual Conference of the International Liver Cancer Association in Chicago, Robin Katie Kelley, MD, argued that the positive outcomes are worth noting and warrant future research into AFP response and at least one area for immediate applicability.

&ldquo;AFP response, defined as a decrease in AFP levels on or after therapy, has been associated with improved survival in patients with HCC treated with local-regional therapies such as chemotherapy, ablation, or surgery,&rdquo; said Kelley, associate professor of clinical medicine in the Department of Medicine (Hematology/Oncology) at University of California San Francisco Helen Diller Family Comprehensive Cancer Center. She added that limited data sets from patients treated with systemic therapies, including retrospective cohorts of patients on either first-line sorafenib (Nexavar) or second-line regorafenib (Stivarga) for advanced HCC, also showed similar findings.

Across disease stages for HCC, elevated levels of serum AFP have indicated poor prognosis. Investigators are hopeful AFP response can eventually serve as a biomarker for treatment efficacy.

Results of the CELESTIAL trial previously showed that cabozantinib significantly improved overall survival (OS) and progression-free survival (PFS) over placebo in patients with previously treated advanced HCC, independent of baseline AFP.  Patients were eligible if they had progressed following at least 1 and up to 2 prior systemic therapies. They were then randomized 2:1 to cabozantinib 60 mg a day versus matched placebo. Tumors were assessed radiographically using RECIST v1.1 every 8 weeks with a primary endpoint of OS and secondary endpoint of PFS.

In the overall study population, patients treated with cabozantinib had a median OS of 10.2 months versus 8.0 months with placebo (HR, 0.76; 95% CI, 0.63-0.92;

= 0.005). Likewise, the median PFS also improved with cabozantinib (5.2 vs 1.9 months; HR, 0.44; 95% CI, 0.36-0.52;

Assessing efficacy by baseline AFP levels, cabozantinib improved OS and PFS compared with placebo across a range of baseline AFP levels. Higher AFP levels were consistently associated with a greater magnitude of benefit with cabozantinib versus placebo.

Another consistent finding was that patients with higher AFP levels treated with cabozantinib had shorter OS and PFS than patients in the low-AFP group (

&ldquo;What these data tell us is that baseline AFP level does not predict for any different response on cabozantinib. Rather, that cabozantinib improves PFS and OS independent of the AFP. Stated another way, this suggests that baseline AFP is not a predictive marker for cabozantinib response,&rdquo; said Kelley.

In the subanalysis, serum AFP level was assessed at baseline and every 8 weeks during treatment. It&rsquo;s important to note that both patients and providers were blinded to central AFP results, said Kelley.

Changes in AFP levels were assessed in patients with evaluable baseline AFP &ge;20 ng/mL, with potential for low-level fluctuations for patients with chronic liver disease or viral hepatitis. This cutpoint was arbitrary, said Kelley, and based solely on previously used cutpoints in the literature. One aim of future studies, she said, should be to focus on defining and validating cutpoints for AFP response.

OS and PFS were then analyzed versus AFP response and progression using 2 different cut offs. AFP response was defined as a &ge;20% or &ge;50% decrease from baseline while AFP progression was defined as a &ge;20% or &ge; 50% increase from baseline.

In the overall population, approximately 70% of patients had elevated baseline AFP or evaluable baseline AFP &ge;20 ng/mL. This is consistent with the known distribution of AFP in the advanced HCC population, said Kelley.

About 50% were evaluable for AFP response at week 8. The remaining 50 percent were not evaluable, with 30% excluded because they had AFP levels <20 ng/mL at baseline, and an additional 20% excluded due to baseline AFP above the upper limit of quantification (300,000 for this assay), death, or dropout prior to or missed blood sample at week 8. This may have contributed to study limitations, said Kelley.

A greater proportion of patients had AFP decreases in the cabozantinib arm (n = 236). Patients on the placebo arm (n = 111) had a greater proportion of AFP increases. Fifty percent of patients on cabozantinib had a &ge;20% decrease in AFP, with 28% having a &ge;50% decrease.

A substantially smaller percentage of patients on placebo (13%) had an AFP response &ge;20% decrease, with a 5% subset having a &ge; 50% decrease. Over twice as many patients on placebo had AFP progression compared with cabozantinib (68% vs 31%, respectively). Using the &ge;50% cut point, corresponding rates of AFP progressions were 51% and 20%. The small response on placebo caused the investigators to focus exclusively on the cabozantinib group for further analysis.

The baseline characteristics of the cabozantinib-treated patients were similar for both the AFP-response and nonresponse groups, with males accounting for 79% in both groups and median ages of 62 and 63 years, respectively. Approximately 83% had extrahepatic spread and/or macrovascular invasion, noted Kelley.

The median OS was substantially longer in the AFP-response group at 16.1 months compared with 9.1 months in those without an AFP response (HR, 0.61; 95% CI, 0.45-0.84). Median PFS was also longer for patients with AFP response compared with those without response (7.3 vs 4 months; HR, 0.55; 95% CI, 0.41-0.74).

On a multivariable analysis including other established prognostic factorssuch as ECOG performance status, baseline AFP, macrovascular invasion, extrahepatic spread, among others&mdash;AFP response was independently and significantly associated with improvement in OS (HR, 0.60;

Patients with AFP response had longer treatment duration at 5.7 months versus 3.7 months for those without response. The discontinuation rate was 13 percent in both arms which was lower than the overall study population, noted Kelley. AFP response status also contributed to all cause adverse events similar to the overall study population. One notable exception was the rate of diarrhea, which was slightly higher at 17% in the AFP-response group compared with 10% in the all patients. &ldquo;This suggests a longer time on treatment, but the numbers were too small to discern significance,&rdquo; says Kelley.

&ldquo;Further optimal thresholds for AFP evaluability, the optimal cut point and definitions for response and progression, and the optimal time points for measuring response remain to be validated,&rdquo; said Kelley. She concluded that AFP response &ldquo;warrants further evaluation as an early surrogate for response or progression to complement existing radiographic tools while on cabozantinib as well as other systemic therapies for advanced HCC now that there are multiple treatment options available for progression for this population.&rdquo;

Kelley RK, Bocobo AG, Goyal L, et al. Alpha-fetoprotein (AFP) response and efficacy outcomes in the phase 3 CELESTRIAL trial of cabozantinib versus placebo in advanced hepatocellular carcinoma (HCC). Presented at: 13th Annual Conferences of the International Liver Cancer Association; September 20-22, 2019; Chicago, IL. bit.ly/2m1pOR2.

Abou-Alfa GK, Meyer T, Cheng A-L. et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma.

. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. 2018;379(1):54-63. doi: 10.1056/NEJMoa1717002.

Kelley RK, Al-Khoueiry AB, Meyer T, et al. Outcomes by baseline alpha-fetoprotein (AFP) levels in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (HCC).

. 2018;29(suppl 8;abstr 702P). doi: 10.1093/anon/mdy282.085.

Patients with advanced hepatocellular carcinoma treated with cabozantinib had higher alpha-fetoprotein response rates versus those treated with placebo, according to findings of a subanalysis of the phase III CELESTIAL trial.

Author | Rita Colorito

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