J. Forrest

Real World Multi-centre UK Review of Nivolumab Monotherapy in Metastatic Endometrial Cancer With Mismatch Repair Deficiency During COVID-19

Immunotherapy checkpoint inhibition has shown improvement in efficacy and survival in patients with mismatch repair deficient (MMRd) advanced endometrial cancer (mEC) compared to chemotherapy. This is combined with chemotherapy in the first-line setting or as monotherapy in later lines of therapy. To assess the efficacy, survival and toxicity of nivolumab monotherapy in metastatic endometrial cancer (mEC) in both first and later lines of therapy as used in the NICE COVID-19 systemic anti-cancer (SACT) guidelines. A multi-centre retrospective review of mEC patients with associated MMRd who received nivolumab as per NICE COVID NG161 at 10 NHS cancer centres. Patient demographics, molecular classification and previous treatments were recorded in addition to treatment responses, duration of response, overall survival, progression-free survival and toxicities. Kaplan-Meier curves analyse the survival data. 52 patients were identified. Median age was 67 (37-81) years. 87.5% of patients had endometrioid histology and 75% were oestrogen receptor (ER) positive. 10.4% patients were p53 mutated. 33.3% of mEC patients were stage IV at diagnosis. 30 (62.5%) patients received nivolumab as first-line mEC therapy. 33 (68.8%) patients received nivolumab 4-weekly. Treatment response was clinician-observed in 34 (70.8%) patients, with 7 (14.5%) more having stable disease. 52%, 45% and 36% of patients were progression-free at 12, 18 and 24months, respectively. 75%, 55% and 47% of patients were alive at 12, 18 and 24 months. There was no significant difference between survival or response whether nivolumab was given in the first line or subsequent lines. 29 (60.4%) patients have discontinued treatment with 23 (44.2%) being due to progressive disease or death. 18 (37.5%) patients developed G1-2 toxicity, and 3 (6.25%) patients discontinued due to G3 toxicity. This retrospective cohort shows that nivolumab monotherapy has good real-world disease control of mEC patients with MMR deficiency. Toxicity rates were low, and checkpoint monotherapy may be a viable option for selected first-line MMRd mEC patients.

The Royal College of Radiologists National Vulvar Cancer Audit

This audit examined UK vulvar cancer practice from March 2018 to January 2019 and compared it to standards from national and international recommendations. Follow-up data collection in 2020 examined patient outcomes and toxicity. Audit standards were based on Royal College of Radiologists (RCR) guidance and published literature. A web-based questionnaire was sent to the audit leads at all cancer centres in the UK. Prospective data collection included patient demographics, tumour characteristics, radiotherapy indications, dosimetry, timelines, and follow-up data. The audit targets were 95% compliance with the RCR dose/fractionation schemes in definitive and adjuvant patients, 40% use of intensity modulated radiotherapy (IMRT), 100% of radical patients treated as category 1, and 95% use of gap compensation for category 1 patients. 34/54 UK radiotherapy centres (63%) completed data entry for 152 patients. 23 out of 34 (68%) centres submitted follow-up data for 94 patients. One indicator exceeded the audit target: 98% of radical patients received IMRT. The indicators of RCR dose/fractionation compliance for adjuvant/definitive radiotherapy were achieved by 80%/43% for the primary, 80%/86% for elective lymph nodes, and 21%/21% for pathological lymph nodes. The use of concomitant chemotherapy with radical radiotherapy in suitable patients was achieved by 71%. Other indicators demonstrated that 78% were treated as category 1 and 27% used gap compensation. Acute toxicity was mostly related to skin, gastrointestinal, and genitourinary sites. Grade 3 and Grade 4 toxicities were seen at acceptable rates within the radical and adjuvant groups. Late toxicity was mostly grade 0. This audit provides a comprehensive picture of UK practice. IMRT is widely used in the UK, and treatment-related toxicity is moderate. The dose fractionation was very heterogeneous. The designation of vulvar cancer as category 1 was not regularly followed for radical/adjuvant patients, and there was minimal gap compensation during treatment.