Comparison of progression-free survival (PFS) on comprehensive multiplatform profiling-guided therapy to PFS on prior therapy: a pooled analysis from 4 contemporary prospective studies


Chahine G, Nasr F, Dean A, Miranova M, Jameson G, Robert NJ , Gastl G, Zwierzina H


It is expected that the PFS for patients with refractory cancers will decline over subsequent lines of therapy. patients with refractory metastatic cancer have previously been shown to derive some clinical benefit from comprehensive multiplatform profiling of tumor issue. Data from four independent physician-led prospective and prospective-retrospective studies was pooled in an exploratory manner to determine if PFS was improved when patients were treated with molecular profiling-guided therapies compared to PFS on the prior therapies.


Tumor issue specimens from 202 patients were submitted for comprehensive multiplatform profiling (CMP) to a certified referral laboratory (Caris Life Sciences, USA) between March 2010 and December 2016. Treatment selections were based on predictive biomarker status associated with agents with potential clinical benefit. Clinical benefit was defined as a PFS ra[o (=PFS upon treatment according to CMP/ PFS on the prior therapy) ≥ 1.3.


As of December 2016, 157 of 202 (77.8%) profiled patients were treated according to the predictive results, of whom 140 were evaluable. patients had received a median of three prior therapies (range 1-12). The most common tumor types were breast (n=35), colorectal (n=14), NSCLC (n=11) and gastric cancer (n=9). A median PFS of 120 days was observed with CMP-directed therapies compared to 89.5 days in prior therapies (HR=0.70, p=0.0120). Seventy-three of 140 patients (52%) had a PFS ra[o ≥ 1.3. Over 70% of treated patients received chemotherapy alone, while 21% of patients received targeted therapies, either alone or in combination with chemotherapy or hormone therapy.


Contrary to the expected decline in PFS, patients had a beYer outcome when treated with CMP-guided treatments. This was driven by the precision use of available chemotherapeutic resources rather than expensive and often inaccessible targeted therapies. Further prospective work in specific tumor types may help to highlight particular pa[ent populations who might benefit most from CMP guidance.

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