Addition of atezolizumab to chemotherapy and maintenance PARP inhibitor has no benefit in ovarian cancer

Combining atezolizumab with chemotherapy and maintenance PARP inhibitor niraparib in late-relapsing recurrent chemotherapy-sensitive ovarian cancer does not significantly improve progression-free survival (PFS) nor objective response rate (ORR), results of the phase 3 ANITA trial showed.

The standard therapy for ovarian cancer with a treatment-free interval of more than 6 months (late-relapsing) is chemotherapy followed by PARP inhibitor maintenance, in case a response to chemotherapy is observed. Despite a strong preclinical rationale, most previous phase 3 studies failed to show the benefit of the addition of a PD-L1 inhibitor to this standard treatment [1–4].

The current phase 3 ANITA trial (NCT03598270) evaluated the effectiveness of PD-1 checkpoint inhibitor atezolizumab in participants treated with chemotherapy and subsequent maintenance PARP inhibition using niraparib. ANITA enrolled 417 participants with high-grade late-relapsing recurrent ovarian cancer who were randomised 1:1 to 6 cycles of chemotherapy with or without atezolizumab followed by maintenance niraparib with or without atezolizumab in case of chemotherapy sensitivity. The primary endpoint was PFS. Prof. Antonio Gonzalez Martin (Cancer Centre Clinica Universidad de Navarre, Spain) presented the first results [5].

The addition of atezolizumab did not significantly improve median PFS: 11.2 versus 10.2 months (HR 0.89; 95% CI 0.71–1.10; P=0.28). No benefit of atezolizumab was observed in any of the prespecified subgroups, including PD-L1 status. Also, atezolizumab did not improve ORR (45% versus 43%) or any other secondary endpoint available at this point.

Placing these results in the context of other studies on this subject, discussant Prof. Charley Gourley (University Edinburgh, UK) suggested that the (negative) results of ANITA fit the idea that bevacizumab is required to ‘unlock’ the synergy of the PARP inhibitor and immune checkpoint inhibitor combination. The role of bevacizumab in the treatment of this ovarian cancer setting is however not clear [6]. Yet, in both the DUO-O (NCT03737643) and MEDIOLA trials (NCT02734004), triplet therapy (PARP inhibitor, immune checkpoint inhibitor, bevacizumab) showed benefits in ORR or PFS over doublet therapy [6,7].

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   1. Monk BJ, et al. Lancet Oncol. 2021;22(9):1275–1289.
   2. Pujade-Lauraine E, et al. Lancet Oncol. 2021;22(7):1034–1046.
   3. Moore KN, et al. J Clin Oncol. 2021;39(17):1842–1855.
   4. Kurtz JE, et al. J Clin Oncol. 2023;41(30):4768–4778.
   5. Harter P, et al. J Clin Oncol. 2023;41(17_suppl): LBA5506–LBA5506.
   6. Gonzalez Martin A, et al. Atezolizumab (atezo) combined with platinum-based chemotherapy (CT) and maintenance niraparib for recurrent ovarian cancer (rOC) with a platinum-free interval (TFIp) >6 months: Primary analysis of the double-blind placebo (pbo)-controlled ENGOT-Ov41/GEICO 69-O/ANITA phase III trial. Abstract LBA37, ESMO 2023, 20–24 October, Madrid, Spain.
   7. Drew Y, et al. Ann Oncol. 2020;31(suppl_4): S615–S616.

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Posted on 19 December, 202315 February, 2024