The prognostic impact was similar in the KRAS wild-type and mutated subgroups.
This analysis will provide some information concerning the p53-mutated subgroup (80% power to see an increase in the PFS of 30% in arm A to 50% in arm B; hazard ratio, 1.76; alpha, 0.008), but it will be too soon to obtain on the normal p53 subgroup.
The primary endpoints consist of comparison of the progression-free survival (PFS) of patients who received neoadjuvant chemotherapy without taxanes (treatment A) with the PFS of patients who received a chemotherapy with taxanes (treatment B), in both the normal p53 subgroup and in the p53-mutated subgroup.
Given the high similarity in miRNAs expression profiles between 'BRCA1/2-like' BRCAX-C tumours and BRCA1- and BRCA2-mutated tumours, this subgroup of tumours would represent good candidates for resequencing studies focused on the DNA-damage repair pathway.
The presence of CALR alterations in JAK2-mutated ET defines a specific subgroup of patients requiring careful follow-up and management for their increased risk of thrombotic events.
Importantly, IMD-0354 also induced apoptosis at similar levels in both IGHV mutated and unmutated subgroups of CLL cases, indicating that both these prognostic subgroups respond similarly to the effect of IMD-0354.
Analogously, the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib, failed to yield a significantly improved overall survival in patients with refractory non-small cell lung cancer, but did show therapeutic benefit in a subgroup of patients with mutated epidermal growth factor receptor.
One must be wary of trading potency for specificity, as targeting very specific amino acid sequences in highly mutated tumors may result in killing only a subgroup of cells.
In the subgroup of patients without KRAS detectable mutation, we have also found that controlled disease and PFS were significantly improved in TP53 mutated patients when compared with TP53 nonmutated patients.
We also found that TP53-mutated patients had a higher degree of karyotypic complexity than TP53 wild-type patients in the subgroup of patients with CK (90% vs 42.9%, P=0.0005).
