He started off by noting the steady progression of immuno-oncology (IO) earlier in the MIBC disease course. It was first approved as second-line systemic therapy for metastatic bladder cancer, then was integrated as maintenance therapy following chemotherapy with stable disease/partial response. Therefore, it was only natural that it would be evaluated in the perioperative setting.
The first adjuvant study was the IMvigor010.1 This was ultimately a negative phase 3 randomized controlled trial (RCT) of atezolizumab versus observation for MIBC. The full results were presented at ASCO 2020.
This was more recently followed by the CheckMate2742 study of adjuvant nivolumab, which was presented earlier this year at ASCO GU 2021.
This was a positive phase III RCT that demonstrated that median disease-free survival was significantly longer for patients receiving nivolumab (21 months) compared to placebo (11 months; hazard ratio 0.70, 95% confidence interval 0.54-0.89). A similar effect was observed in the PD-L1 ≥ 1% population (hazard ratio 0.53, 95% confidence interval 0.34-0.84).
Importantly, in the subset analysis, patients who received prior neoadjuvant chemotherapy appeared to have a better response than those who did not.
Multiple studies assessed the role of IO therapy in the neoadjuvant setting. These include the ABACUS trial,5 NABUCCO trial,4 and PURE-01 trial,3 among others. The results are generally summarized at a high level below:
Their pathological complete response (PCR) rates are similar.
This has now led to ongoing studies exploring the combination of:
1) IO and chemotherapy
2) IO and antibody-drug conjugate or other IO
His main take-home points:
1) Neoadjuvant chemotherapy is still the standard of care for MIBC
2) Adjuvant nivolumab improves DFS in PD-L1+ patients and in ITT population
- Overall survival data needed
- Unclear why atezolizumab did not work
3) Neoadjuvant IO is (very) active
- Able to beat chemotherapy – or is combined with chemotherapy when needed?
- Role of (high-dose) anti-CTLA4? Needs to be addressed.
Presented by: Michiel S. Van Der Heijden, MD, Ph.D, Medical Oncologist and Research Group Leader, both at the Netherlands Cancer Institute (NKI) Amsterdam, Netherlands
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.
References:
1. Bellmunt J, Hussain M, Gschwend JE, et al.; IMvigor010 Study Group. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):525-537. doi: 10.1016/S1470-2045(21)00004-8. Epub 2021 Mar 12. PMID: 33721560.
2. Bajorin DF, Witjes JA, Gschwend JE,et al.. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021 Jun 3;384(22):2102-2114. doi: 10.1056/NEJMoa2034442. PMID: 34077643; PMCID: PMC8215888.
3. Necchi A, Anichini A, Raggi D, et al.. Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol. 2018 Dec 1;36(34):3353-3360. doi: 10.1200/JCO.18.01148. Epub 2018 Oct 20. PMID: 30343614.
4. van Dijk N, Gil-Jimenez A, Silina K, et al. Hooijberg E, Schumacher TN, van den Broek M, Wessels LFA, Blank CU, van Rhijn BW, van der Heijden MS. Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial. Nat Med. 2020 Dec;26(12):1839-1844. doi: 10.1038/s41591-020-1085-z. Epub 2020 Oct 12. PMID: 33046870.
5. Powles T, Kockx M, Rodriguez-Vida A, Duran I, et al.. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov;25(11):1706-1714. doi: 10.1038/s41591-019-0628-7. Epub 2019 Nov 4. Erratum in: Nat Med. 2020 Jun;26(6):983. PMID: 31686036.