The invited discussant for the CodeBreaK 200 trial, Jarushka Naidoo, MBBCh, MHS, Professor of Medical Oncology and Consultant Medical Oncologist at Beaumont RCSI Cancer Centre in Dublin, underscored the importance of patient-reported outcomes in evaluating the effectiveness of oncology treatments, citing previous research by Ethan Bash, Michelle DeMarco, and others. This research has shown the value of patient-reported outcomes in accurately representing patients’ experiences and symptom burdens compared with clinician reporting.

Jarushka Naidoo, MBBCh, MHS

Dr. Naidoo noted that although sotorasib demonstrated improvements in patient quality of life and symptom benefits, questions remain about its overall survival benefit. “We see that patients indeed live better as a result of sotorasib, but are they necessarily living longer? We have not yet seen an overall survival benefit,” said Dr. Naidoo. “The comparator arm, docetaxel, is weak when it comes to quality of life, which may affect our interpretation of these results.”

In addition, Dr. Naidoo pointed out that the minimum important difference between the quality-of-life measures and what truly constitutes a clinically significant difference for the patient is still undefined. This further complicates the interpretation of the trial results, she said, emphasizing the need for more research in this area.

Other Unanswered Questions

Dr. Naidoo also noted the need for further research to determine the optimal use of KRAS G12C agents such as sotorasib and adagrasib, whether as monotherapy, combination therapy, or in different lines of treatment. “It will be important to compare patient-reported outcomes data between different KRAS G12C agents, both approved and in clinical development, to inform future treatment decisions,” she explained.

Finally, Dr. Naidoo highlighted the importance of understanding how specific patient populations, such as those with a poor Eastern Cooperative Oncology Group performance status and brain metastases, fare in terms of patient-reported outcomes, survival, and response. “As we move forward in this field, a more nuanced understanding of the benefits and limitations of sotorasib and other KRAS G12C inhibitors is essential for optimizing patient care,” she concluded. 

DISCLOSURE: Dr. Naidoo reported financial relationships with Merck, AstraZeneca, Roche/Genentech, Pfizer, Takeda, Bayer, Daiichi Sankyo, Kaleido Biosciences, NGM Pharmaceuticals, Amgen, Regeneron, Elevation Oncology, AbbVie, Arcus Biosciences, Mirati, Bristol Myers Squibb, Medscape, OncLive, Research to Practice, and Touch Oncology.