(P 271) ORAL VINORELBINE IN DESMOID TUMOURS; A SINGLE CENTRE RETROSPECTIVE ANALYSIS

Objective: Desmoid Tumours (DT) are a group of rare (0.03% of total neoplasms) benign tumours arising from fibroblasts that can exhibit locally aggressive behaviour. Single agent oral vinorelbine (90mg day 1, 8 and 15 of a 28-day cycle) has emerged as a simplified, less toxic and more manageable alternative to the standard pharmacological approach with two-weekly IV methotrexate and vinblastine/vinorelbine in patients with aggressive or refractory disease. The real-world efficacy and safety of oral vinorelbine in DT needs to be established.

Methods: We retrospectively analysed clinical data, imaging and chemotherapy records for teenage and young adult (TYA) and adult DT patients treated with oral vinorelbine within the London Sarcoma Service (LSS) from January 2020 to June 2022.
Inclusion criteria: patients receiving 3+ cycles (or until the first documented radiographic assessment, whichever occurred first).
Routine weekly full blood count (FBC) and biochemistry for the first three cycles, and once monthly thereafter were assessed for blood dyscrasias. Other side effects were also recorded.

Results: Forty-two patients were identified; thirty-seven met the inclusion criteria and were analysed. Twenty-eight patients were female, with a median age of 33 years (range 17 – 62 years).

Twelve patients (32%) had symptomatic improvement following initiation of treatment; nine of which had no initial radiological response. Symptoms progressed on treatment for two patients (5%) following three cycles and treatment was stopped. Symptoms stabilised for the remainder of patients (N=23; 62%).

Six patients (16%) had a radiological partial response (PR) to treatment at first imaging. Twenty-five patients (68%) had stable disease (SD) and four (11%) had progressive disease (PD). One patient had a mixed response and vinorelbine was continued due to symptomatic benefit with further response on the next imaging.

All patients on line 2+ of treatment had stable or improved symptoms (N=20, 54%). Imaging for all but one of these patients also confirmed SD or PR. The median line of treatment was 2 (range 1-4).

The median time on treatment was 7 months (range 3 – 14 months). Seven patients (19%) remain on treatment, with thirty patients (81%) being off treatment. Fourteen patients (38%) completed 1 year of oral vinorelbine and therapy was therefore stopped. The reasons that patients stopped treatment prior to receiving a year of therapy are outlined in Table 1.

One episode of grade 3 (G3) neutropenia was observed after seven cycles of treatment. Otherwise, FBC and biochemistry were stable throughout treatment. One patient had low haemoglobin at baseline requiring multiple blood transfusions. This occurred in the context of poor baseline renal function that remained unchanged throughout.

The main reported toxicities were - G1 diarrhoea (5, 14%), nausea (G1 - 12, 32%; G2 – 2, 5%); G1 fatigue (16, 43%) and constipation (G1 – 3, 8%, G2 - 4, 11%). One patient suffered from stomach cramps that improved with dose reduction to treatment given on D1 and D15 only, following cycle 3.

Conclusion: Despite the limitations of a retrospective analysis we believe that single agent oral vinorelbine is an effective and safe treatment option for the management of newly diagnosed or refractory DT in the TYA and adult population. Over a third of patients completed 1 year of oral vinorelbine with radiological and clinical benefit. Initially monthly blood tests were assessed during 2020-2021. Blood counts and biochemical values were found to be stable throughout treatment and therefore we suggest monitoring every 3 cycles. Most toxicities were grade 1 and did not require dose reduction nor discontinuation.

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