Real-world efficacy and safety of durvalumab-tremelimumab as second-line systemic therapy after atezolizumab-bevacizumab in unresectable hepatocellular carcinoma

Abstract

The efficacy and safety of immune-checkpoint inhibitors (ICI) for the treatment of unresectable hepatocellular carcinoma are known. We explored ICI rechallenges with direct switching from 1 ICI regimen to another. This retrospective study included 16 patients who received atezolizumab-bevacizumab (Atezo+Bev) and durvalumab-tremelimumab (Dur+Tre) as the first-line and second-line combination therapy, respectively, at Hiroshima University Hospital. The radiological response and adverse event were evaluated in all patients. Of the 16 patients, 12 were male, and the median age at Atezo+Bev induction was 71 years. The reasons for medication changes were disease progression in 11 patients and adverse events in 5 patients. With Atezo+Bev and Dur+Tre initiation, the Barcelona-Clinic Liver-Cancer stage (A/B/C) progressed in 9/6/3 and 3/4/9 patients and the Child-Pugh classification (A/B/C) progressed in 12/4/0 and 9/6/3 patients, respectively. The disease control rate and overall response rate of Atezo+Bev were 87.5% and 58.3%, respectively, and of Dur+Tre were 62.5% and 0%, respectively. The most common immune-related adverse event in both the Atezo+Bev and Dur+Tre groups was colitis; 3 of the 5 patients with colitis on Atezo+Bev treatment had colitis with Dur+Tre, and 2 had exacerbations. Regarding liver function, ALBI score significantly decreased during Atezo+Bev, but not Dur+Tre, treatment. In patients with colitis following Atezo+Bev, subsequent Dur+Tre treatment may induce colitis recurrence or exacerbation. For immune-related adverse events other than colitis, Dur+Tre could provide relatively safe disease control while maintaining liver function.

Figure 1.

Swimmer plot describing the treatment course, date of onset of adverse events, radiological response, and response date of 16 cases. Colored solid bars: red, Atezo+Bev administration period; yellow, Atezo administration period; blue, Dur+Tre administration period; white, untreated period. Blue circle: CR. Blue triangle: PR. Red squares: SD, Red rhombi: PD. Black square: Death. Arrow: Ongoing treatment. Hyphen-Minus; TACE or TAI. Asterisk: Adverse events of CTCAE Grade 3. Atezo+Bev = atezolizumab–bevacizumab combination therapy, CR = complete response, CTCAE = Common Terminology Criteria for Adverse Events, DCR = disease control rate, Dur+Tre = durvalumab–tremelimumab combination therapy, ORR = overall response rate, PD = progressive disease, PR = partial response, SBRT = stereotactic body radio therapy, SD = stable disease, TACE = transarterial chemoembolization, TAI = transarterial infusion chemotherapy.

Figure 2.

BOR at Atezo+Bev and Dur+Tre in 16 cases of the cohort. (A) BOR at Atezo+Bev and Dur+Tre, (B) BOR at Dur+Tre according to BOR at Atezo+Bev, (C) BOR at Dur+Tre according to DCR at Atezo+Bev, and (D) BOR at DUR+TRE by reason of discontinuation of Atezo+Bev. The significance threshold was set at a P ≤ .05. Atezo+Bev = atezolizumab–bevacizumab, CR = complete response, DCR = disease control rate, Dur+Tre = durvalumab–tremelimumab, NE = not evaluable, PD = progression of disease, PR = partial response, SD = stable disease.

Figure 3.

Waterfall plots of the percentage in target tumor from baseline by treatment. The y-axis represents the treatment-induced change in the target lesion from baseline. Treatments have been differentiated using different threads and irAEs are displayed on a color scale. Negative/positive values represent maximum tumor reduction or minimum tumor increase, respectively. Colored solid bars: red indicates Atezo+Bev and blue indicates Dur+Tre. Colored scale represents the CTCAE grade of irAEs. Atezo+Bev = atezolizumab–bevacizumab combination therapy, CR = complete response, CTCAE = Common Terminology Criteria for Adverse Events, DCR = disease control rate, Dur+Tre = durvalumab–tremelimumab combination therapy, IrAE = immune-related adverse event, PD = progression of disease, PR = partial response, SD = stable disease.

Figure 4.

TRAE and irAE at Atezo+Bev and Dur+Tre in 16 cases of the study cohort. List of TRAEs and irAEs that occurred during the observation period. The CTCAE grade for each case is displayed on a color scale. AB = atezolizumab–bevacizumab combination therapy, CTCAE = Common Terminology Criteria for Adverse Events, DT = durvalumab–tremelimumab combination therapy, IrAE = immune-related adverse events, TRAE = treatment-related adverse events.

Figure 5.

Box plot of changes in the ALBI score during the observation period. The BOX plot depicts the change in the ALBI score from the start of Atezo+Bev, 6 mo after the start of Atezo+Bev treatment, at the end of Atezo+Bev, at the start of Dur+Tre, at the end of Dur+Tre, or at the end of observation. The significance threshold was set at P ≤ .05. ALBI = albumin–bilirubin, Atezo+Bev = atezolizumab–bevacizumab combination therapy, Dur+Tre = durvalumab–tremelimumab combination therapy.