Personalized Medicine Approach Not Straightforward in Glioblastoma

Personalized Medicine Approach Not Straightforward in Glioblastoma
Personalized Medicine Approach Not Straightforward in Glioblastoma

CHICAGO — The role of antiangiogenic agents continues to evolve in the treatment of CNS cancers, attendees at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting were told.

Summarizing the results of 3 posters, discussion session discussant John de Groot, MD, University of Texas MD Anderson Cancer Center, said that the personalized medicine approach is not straightforward in glioblastoma; in addition, biomarkers that can identify patients who may benefit from treatment may not be obvious.

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He outlined results from the first study, by Wick et al,1 a phase 2 trial that examined the sequence of bevacizumab and lomustine in patients with first glioblastoma recurrence. Results showed all of the study arms had overall survival rates lower than 27% and therefore did not meet the primary efficacy criterion.

Dr. de Groot noted the high bevacizumab use at recurrence in all study arms, 20% to 40% of patients. Since early bevacizumab use does not appear to worsen overall survival, does this mean we “need to rethink excluding bevacizumab in recurrent disease clinical trials?”

In a retrospective analysis of AVAglio, Chinot et al2 looked at whether baseline MMP9 could predict overall survival benefit from treatment with bevacizumab in newly diagnosed glioblastoma. Results suggested that patients with low plasma MMP9 levels at baseline may benefit from the addition of bevacizumab to radiotherapy and temozolomide.

Dr. de Groot asked, “why would MMPs predict outcome on bevacizumab? Do changes in MMP9 following treatment add predictive value? Does low MMP9 correlate with lower vascular permeability, minimal residual tumor volume?” This needs prospective validation, he said.

The third study, by Ellingson et al,3 looked at residual tumor volume and change in tumor volume during adjuvant therapy to predict long-term survival in AVAglio. They found baseline postoperative tumor volume to be prognostic as well as an increase in tumor volume after initial treatment, resulting in a significantly shorter overall survival, which was masked by bevacizumab use. He asked how these data can be interpreted with respect to pseudoprogression on postradiotherapy MRI, adding, “validation is important.”

A role for bevacizumab may include other, nontumor benefits, such as steroid sparing, treatment of radiation-induced necrosis, or maintenance/decrement in quality of life. Next generation combinations include immunotherapy and viral therapy or use in difficult treatment situations, such as in brainstem and thalamic tumor or in poor performance patients—or in subsets of biomarker-positive patients.

Challenges and opportunities that remain in determining a place for antiangiogenic therapies include the early identification of biomarkers in preclinical trials; the integration of biomarkers into phase 1 and 2 trial designs; and definitive testing in randomized adaptive phase 3 trials, Dr. de Groot concluded.

References

1. Wick W, Stupp R, Gorlia T, et al. Phase II part of EORTC study 26101: the sequence of bevacizumab and lomustine in patients with first recurrence of a glioblastoma. Poster presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.

2. Chinot OL, Garcia J, Romain S, et al. Baseline MMP9 to predict overall survival benefit from bevacizumab in newly diagnosed glioblastoma: a retrospective analysis of AVAglio. Poster presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.

3. Ellingson BM, Garcia J, Revil C, et al. Residual tumor volume and change in tumor volume during adjuvant therpay to predict long-term survival in AVAglio. Poster presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.

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