Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2024

Health-Related Quality-of-Life in Neoadjuvant Combinations of Immunotherapy in BRAFV600-Mutant Resectable Melanoma: Results from the Randomised Phase II NeoTrio Trial (#554)

Jake R Thompson 1 2 , Matteo S Carlino 1 2 3 4 , George Au-Yeung 5 6 , Andrew J Spillane 1 2 7 8 , Kerwin F Shannon 1 2 8 9 10 11 , David E Gyorki 5 6 , Edward Hsiao 7 , Rony Kapoor 8 12 , Julie Howle 3 , Sydney Ch'ng 1 2 8 9 10 , Maria Gonzalez 1 , Robyn PM Saw 1 2 8 9 , Thomas Pennington 1 2 8 9 , Serigne N Lo 1 2 , Richard A Scolyer 1 2 9 13 14 , Alexander M Menzies 1 2 7 8 , Georgina V Long 1 2 7 8 13
  1. Melanoma Institute Australia, Wollstonecraft, NSW, Australia
  2. The University of Sydney, Sydney, NSW, Australia
  3. Westmead Hospital, Westmead, NSW, Australia
  4. Blacktown Hospital, Blacktown, NSW, Australia
  5. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  6. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia
  7. Royal North Shore Hospital, Sydney, NSW, Australia
  8. Mater Hospital, Sydney, NSW, Australia
  9. Royal Prince Alfred Hospital, Sydney, NSW, Australia
  10. Chris O'Brien Lifehouse, Sydney, NSW, Australia
  11. Concord Repatriation Hospital, Concord, NSW, Australia
  12. I-MED Radiology Network, Mater Hospital, Sydney, NSW, Australia
  13. Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
  14. NSW Health Pathology, Sydney, NSW, Australia

Aims

We investigated the health-related quality of life (HRQoL) impacts of neoadjuvant combinations of immunotherapy and targeted therapy in melanoma patients.

Methods

The NeoTrio phase II trial included patients with resectable stage III BRAFV600-mutant melanoma randomised to receive sequential (SEQ) therapy (dabrafenib-trametinib, followed by pembrolizumab), concurrent (CON) therapy (dabrafenib-trametinib-pembrolizumab), or pembrolizumab alone (ALO) for 6 weeks followed by surgery (therapeutic lymph node dissection). HRQoL outcomes were measured at baseline and 6-week intervals for 60 weeks using the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire and Functional Assessment of Cancer Therapy Melanoma Surgery Subscale. Analyses included mixed linear modelling and time to first deterioration.

Results

Baseline and ≥1 follow-up data were available for 19 (95%) SEQ, 20 (100%) CON, and 19 (95%) ALO patients. Drug-related toxicity rates were 95%, 100%, and 85%, and surgical adverse events occurred in 80%, 42%, and 83% of patients, respectively. Statistically significant deteriorations in HRQoL were observed in the perioperative period, with CON patients reporting a deterioration (-10.83, 95% CI: -19.65, -2.01) at week 6 (pre-surgery) likely due to the high rate of drug-related toxicity. SEQ patients reported a deterioration (-16.37, 95% CI: -19.65, -2.01) at week 12, and ALO patients reported deteriorations at week 12 (-17.70, 95% CI: -25.10, -10.30) and week 30 (-11.95, 95% CI: -21.01, -2.87). Deteriorations at week 12 in the SEQ and ALO cohorts were clinically significant, likely due to higher rates of surgical adverse events compared with CON patients. Otherwise, baseline levels of HRQoL were maintained for the SEQ and CON cohorts, whereas HRQoL remained decreased from baseline for ALO patients.

Conclusion

Melanoma patients treated with sequential or concurrent BRAF-targeted therapy and immunotherapy maintain baseline HRQoL throughout the first 60 weeks of treatment, apart from the perioperative period where HRQoL deteriorates.