Where’s the Proof? Clinical Trials and Cancer Testing

Numerous trials have been conducted to assess the predictive validity of the Rational Therapeutics Ex-Vivo Analysis of Programmed Cell Death (EVA-PCD®) and similar platforms. However, we (and other investigators) are sometimes dismissed for lack of data supporting the validity of our methods.  Despite the unwillingness of the cooperative groups to formally test laboratory-directed therapy against standard protocol treatments, we have compiled a compelling collection of both retrospective and prospective correlative analyses that strongly support the clinical utility of these methodologies.

Two of the trials that I’ve reported prospectively compared the results of the EVA-PCD platform with objective response, time to progression and survival. The findings in breast cancer confirmed a significant correlation between drug sensitivity and progression-free survival in the evaluation of cisplatin plus gemcitabine (Nagourney et al, JCO 2000).

A second study conducted in ovarian cancer established the correlation between sensitivity and objective response, time to progression and overall survival (Nagourney et al, Gyn Onc 2003). More recently, a laboratory-directed protocol in NSCLC provided an objective response rate of 62 percent, statistically significantly superior to standard outcomes (p=0.003), with a median progression-free survival of 9.5 months and median overall survival of 22.3 months.

We and other investigators in the field have made it abundantly clear that we are very willing to participate in well-conducted formal studies. Amongst the organizations that have been approached to conduct such studies — NSABP, GOG, ECOG and CCG — have all been unwilling to undertake confirmatory studies. The costs of prospective clinical trials (now in the range of millions of dollars) remain a substantial hurdle for investigators in this field. Nonetheless, a fair test of these methodologies should be conducted.