Phase I clinical trial outcomes in 93 patients with brain metastases: The M. D. Anderson Cancer Center experience.

e16546 Background: Patients with brain metastases are often excluded from clinical trials, but it is unclear if they pose an enhanced risk. METHODS We reviewed the records of 1,181 consecutive patients with and without brain metastases treated in the Phase I Clinical Trials Program. We compared clinical outcomes in patients who presented with and without brain metastases during the same time period. RESULTS Of 1,181 patients, 93 had brain metastases at the time of referral (median: age, 54 yrs, number of prior therapies, n=4). The rates of stable disease ≥ 4 months/ partial/ complete response in patients with and without brain metastases were 17% and 27%, respectively (p= 0.03). Although the median survival for patients with brain metastases was shorter than for that of patients without brain metastases (7.5 vs. 10.3 months; p = 0.002), in multivariate analysis the presence of brain metastases was not an independent factor predicting survival. There was no difference in time-to-treatment failure (TTF) (1.74 vs. 1.84 months, respectively; p = 0.61) or in Grade 3-4 toxicity (including neurologic) between patients with and without brain metastases (12% vs. 10%, p = 0.77). When treatment-related neurotoxicity ≥Grade 3-4 was compared between 93 patients with brain metastases and 527 patients without brain metastases treated in the same protocols, the respective rates were 4.3% (n=4) and 2.27% (n=12) (p 0.435). CONCLUSIONS The rates of survival and response of patients with brain metastases were lower than those for other patients in the Phase I setting, but the presence of brain metastases was not an independent prognostic factor predicting survival, indicating that other covariates that co-exist with brain metastases were more significant. TTF for patients with brain metastases was not decreased, nor was the incidence of serious side effects (including neurotoxicity) increased, suggesting that these patients should be eligible for early clinical trials.