Atezolizumab may not lower recurrence risk after resection of renal carcinoma, show trial results

USA: The results of a multicentre, randomized, double-blind, phase 3 trial published in The Lancet have evaluated the role of Atezolizumab as "non-supportive" for adjunctive therapy after resection in renal carcinoma (RCC) patients at high risk of recurrence.

Renal cell carcinoma (RCC) is a common malignancy originating from the cortex of the kidney and shows male predilection in the age group 50-70 years. The various risk factors associated are hypertension, higher BMI, polycystic kidney disease, etc., in elderly males. The carcinoma spreads to the lung, bones, liver, and brain. The metastasis usually occurs within five years of nephrectomy.

A study published by Dr. Rini et al. and team in 2019 supported a combination of Atezolizumab plus bevacizumab. It was proposed that it as a first-line treatment in managing selected patients with advanced renal cell carcinoma (IMmotion151). A clinical trial led by Dr. Lafon and the team concluded that" for Atezolizumab combined with an antiangiogenic agent, the overall survival in the global population did not meet the criteria for significance at the time of the intermediate analysis."

As per the literature, despite adherence to the guidelines, the RCC recurrence remains unnoticed in 33 % of cases.

Considering the above background, a study was conducted by Dr. Pal from the Department of Medical Oncology at City of Hope Comprehensive Cancer Center with a team of the researcher to evaluate whether atezolizumab could be supportive as an adjuvant for RCC patients at increased risk of recurrence after resection. Investigator-assessed disease-free survival in the intention-to-treat population was determined as the primary endpoint. The comparison was made between the intervention group and the control group.

Stratification factors were included as follows:

The stage of disease, T2 or T3a vs. T3b-c or T4 or N+ vs. M1, no evidence of disease

The geographical region included North America and excluded Mexico vs. the rest of the world)

PD-L1 status on tumor-infiltrating immune cells (<1% vs.≥1% expression).

The critical points of the study are:

• The trial was conducted in 28 countries at 215 centers.
• The study included 788 RCC patients aged 18 years or older with sarcomatoid components and an increased risk of recurrence.
• The randomization was done in 1:1 in two groups (atezolizumab and placebo) with an interactive voice-web response system after nephrectomy with or without metastasectomy.
• The Atezolizumab group had 390 patients, and the placebo had 388 patients.
• The intervention group received 1200 mg atezolizumab intravenously and a placebo (Intravenously) once every three weeks for 16 cycles or one year.
• The follow-up period was 44·7 months.
• With atezolizumab, the Median investigator-assessed disease-free survival was 57·2 months, while for placebo, it was 49·5 months. The hazard ratio was 0·93, and the p-value was 0·50.
• The adverse events commonly reported (Atezolizumab vs placebo )were hypertension (2% vs 4%) , hyperglycaemia (3% vs 2%), and diarrhoea (1% vs 2%).
• Overall, 18% in the atezolizumab group and 12% in the placebo group had a serious adverse event.
• No death related to treatment were reported.

The authors said surgery is the standard of care for localized RCC, and recurrence usually occurs after five years of surgery, so we determined the adjunctive role of Atezolizumab in RCC patients to enquire about its supportive role in patients at higher risk of recurrence. We aimed to examine if recurrence could be delayed in such patients.

Atezolizumab was associated with non-significantly increased disease-free survival compared to the placebo (57.2 months vs. 49.5 months) and more serious adverse events than the placebo.

The final words by the team of researchers could be summarised as, " We do not report any evidence of improved clinical outcomes using Atezolizumab as adjuvant therapy after resection in RCC patient at increased risk of recurrence. The results of our study do not support adjuvant atezolizumab for management of RCC."

The study acknowledged F Hoffmann-La Roche and Genentech, a member of the Roche group, as a source of funding.

Further reading:

Pal SK, Uzzo R, Karam JA, Master VA, Donskov F, Suarez C, Albiges L, Rini B, Tomita Y, Kann AG, Procopio G, Massari F, Zibelman M, Antonyan I, Huseni M, Basu D, Ci B, Leung W, Khan O, Dubey S, Bex A. Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomized, double-blind, phase 3 trial. Lancet. 2022 Oct 1;400(10358):1103-1116. DOI: 10.1016/S0140-6736(22)01658-0. Epub 2022 Sep 10. PMID: 36099926.