KEY TAKEAWAYS
- Atezo + bev combination therapy approved globally for unresectable HCC patients who have not received prior systemic therapy based on the Phase Ib IMbrave150 study results.
- The study data (Lee Lancet Oncol 2020) showed that adding bev to atezo has a clinically relevant contribution to the immune enhancement and normalization of tumor blood vessels in HCC patients.
- This study aimed to explore whether skipping bev due to bev affects the efficacy of atezo + bev in HCC patients.
- To minimize immortal time bias, Landmark analyses of OS and PFS were performed in patients who received atezo + bev for ≥6 months.
- The results suggest that skipping bev did not significantly impact the efficacy of atezo + Bev. However, the non-randomized and exploratory nature should be acknowledged.
Based on Phase 3 IMbrave150 research results, atezo (atezolizumab) + bev (bevacizumab) treatment has been approved worldwide for unresectable hepatocellular carcinoma (HCC) who have not yet undergone systemic therapy (NCT03434379, Finn NEJM 2020 and Cheng J Hepatol 2022). In addition, data from Phase 1b research (Lee Lancet Oncol 2020) suggest that Bev’s contribution to a regimen containing atezo is clinically meaningful, particularly regarding immunological augmentation and normalization of tumor blood vessels.
However, the effect of skipping bev because of bev AESIs on the efficacy of atezo + bev remains uncertain. Using information from the IMbrave150 study, they compared outcomes between patients who had skipped bev with those who had never skipped Bev.
Patients were randomly randomized to receive atezo + bev in Arm A of IMbrave150. Patients who had ever had a bev skipped because to bev AESIs were included in Group A-1. The patients not qualifying for inclusion in Group A-1 made Group A-2. Patients who received atezo + bev for 6 months were included in landmark analyses of overall survival (OS) and progression-free survival (PFS) to account for immortal time bias.
Around 210 patients were given atezo + bev for at least 6 months, with 69 assigned to group A-1 and 141 assigned to group A-2. The distribution of the baseline attributes did not show any apparent variations between the groups. Patients in group A-1 had a BCLC stage of C at 75.4% and were Child-Pugh A5 at 76.8%, while those in group A-2 had an 80.1% BCLC stage and were Child-Pugh A5 at 77.0%. Median overall survival (OS) for groups A-1 and A-2 at the data cutoff (Aug 20, 2020) was 25.8 and 26.2 months, respectively (HR, 1.04; 95% CI, 0.64 to 1.69). Median progression-free survival (PFS) was 15.5 and 10.0 months, respectively (HR, 1.07; 95% CI, 0.74 to 1.55).
In this post hoc analysis, patients who had ever missed a bev did not do any worse than those who had never missed a bev. It is important to note that this comparison was not randomized or exploratory. Still, the data nevertheless indicate that skipping bev did not significantly affect the efficacy of atezo + Bev.
Source:https://meetings.asco.org/abstracts-presentations/215564
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03434379
Kudo, M., Tsuchiya, K., Shao, Y.Y., Finn, R.S., Galle, P.R., Ducreux, M., Cheng, A.-L., Yamashita, T., Koga, H., Aoki, K., Yamada, K., Asakawa, T., Nakagawa, Y. and Ikeda, M. (2023). IMbrave150: Exploratory analysis to examine the association between bevacizumab (bev) ever being skipped and bev never being skipped in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab (atezo) + bev in a global phase 3 study. Journal of Clinical Oncology, 41(4_suppl), pp.538–538. doi:https://doi.org/10.1200/jco.2023.41.4_suppl.538.
