Treatment of newly diagnosed ovarian cancer

Addition of atezolizumab to standard first-line chemotherapy did not increase progression-free survival (PFS) of patients with ovarian cancer. The SOLO1 trial showed impressive 5-year follow-up data.

Platinum-taxane chemotherapy in combination with bevacizumab is an established front-line regimen for ovarian cancer in advanced stage setting. Blocking tumour-associated VEGF may promote T-cell infiltration into the tumour and boost immune responses [1]. This justifies combining anti-VEGF and anti-PD-(L)1 therapy. In the randomised, phase 3 IMagyn050 trial, 1,301 newly diagnosed patients with stage III/IV ovarian cancer (75% high-grade serous) were randomised to receive standard regimen (paclitaxel, carboplatin, bevacizumab) or the same regimen plus atezolizumab (200 mg every 3 weeks) [2]. The treatment was neoadjuvant and adjuvant (post-surgery) in 25% and 75%, respectively.

There was no statistically significant PFS improvement in either the ITT population (median 19.5 months with atezolizumab vs 18.4 months with placebo; HR 0.92) or the PD-L1-positive population (n=784; median 20.8 vs 18.5 months, respectively; HR 0.80). Exploratory PFS analyses in the subgroup with PD-L1-positive immune cell count ≥5% (n=260) showed a trend favouring atezolizumab (HR 0.64; P=0.027). Though immature, first interim overall survival (OS) results did not show significant benefit from atezolizumab. The safety profile of atezolizumab plus bevacizumab plus chemotherapy was consistent with expected adverse events. Exploratory biomarker subgroup analyses are ongoing.

Newly diagnosed advanced ovarian cancer patients are at high risk of relapse and 5-year survival averages 30–50%. In the phase 3 randomised SOLO1 trial, patients with ovarian cancer and a mutation in BRCA1 or BRCA2 who were in response after first-line platinum-based chemotherapy derived PFS benefit from maintenance with olaparib [3]. Now, 5-year follow-up data are available [4].

A total of 260 patients were randomised to olaparib (300 mg tablets twice daily) and 131 to placebo for up to 2 years or until progression. After a median of 4.8 and 5.0 years of follow-up, median PFS was 56 versus 13.8 months for olaparib and placebo, respectively (HR 0.33; 95% CI 0.25-0.43). At 5 years, 48.3% of patients treated with olaparib remained free from disease progression versus 20.5% on placebo. The safety profile of olaparib was consistent with previous observations.

1. Wallin JJ, et al. Nat Commun 2016;7:12624
2. Moore K, et al. Primary results from IMagyn050/GOG 3015/ENGOT-OV39, a double-blind placebo (pbo)-controlled randomised phase III trial of bevacizumab (bev)-containing therapy +/- atezolizumab (atezo) for newly diagnosed stage III/IV ovarian cancer (OC). ESMO 2020 Virtual Meeting, abstract LBA31.
3. Moore, K, et al. N Engl J Med 2018;379:2495-2505.
4. Banerjee S, et al. Maintenance olaparib for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): 5-year (y) follow-up (f/u) from SOLO1. ESMO 2020 Virtual Meeting, abstract 811MO

Posted on 25 November, 202016 February, 2024