FAIRLANE, a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer.

BACKGROUND: This hypothesis-generating trial evaluated neoadjuvant ipatasertib-paclitaxel for early triple-negative breast cancer (TNBC). PATIENTS AND METHODS: In this randomized phase II trial, patients with early TNBC (T ≥ 1.5 cm, N0-2) were randomized 1 : 1 to receive weekly paclitaxel 80 mg/m2 with ipatasertib 400 mg or placebo (days 1-21 every 28 days) for 12 weeks before surgery. Co-primary end points were pathologic complete response (pCR) rate (ypT0/TisN0) in the intention-to-treat (ITT) and immunohistochemistry phosphatase and tensin homolog (PTEN)-low populations. Secondary end points included pCR rate in patients with PIK3CA/AKT1/PTEN-altered tumors and pre-surgery response rates by magnetic resonance imaging (MRI). RESULTS: pCR rates with ipatasertib versus placebo were 17% versus 13%, respectively, in the ITT population (N = 151), 16% versus 13% in the immunohistochemistry PTEN-low population (N = 35), and 18% versus 12% in the PIK3CA/AKT1/PTEN-altered subgroup (N = 62). Rates of overall and complete response (CR) by MRI favored ipatasertib in all three populations (CR rate 39% versus 9% in the PIK3CA/AKT1/PTEN-altered subgroup). Ipatasertib was associated with more grade ≥3 adverse events (32% versus 16% with placebo), especially diarrhea (17% versus 1%). Higher cycle 1 day 8 (C1D8) immune score was significantly associated with better response only in placebo-treated patients. All ipatasertib-treated patients with low immune scores and a CR had PIK3CA/AKT1/PTEN-altered tumors. CONCLUSIONS: Adding ipatasertib to 12 weeks of paclitaxel for early TNBC did not clinically or statistically significantly increase pCR rate, although overall response rate by MRI was numerically higher with ipatasertib. The antitumor effect of ipatasertib was most pronounced in biomarker-selected patients. Safety was consistent with prior experience of ipatasertib-paclitaxel. A T-cell-rich environment at C1D8 had a stronger association with improved outcomes in paclitaxel-treated patients than seen for baseline tumor-infiltrating lymphocytes. This dependency may be overcome with the addition of AKT inhibition, especially in patients with PIK3CA/AKT1/PTEN-altered tumors. CLINICALTRIALS.GOV: NCT02301988.

T cell leukemia--lymphoma in young adults.

The clinical, pathologic, immunologic and electron microscopic findings in three cases of young men who had T cell leukemia and lymphoma are presented. The disease in this older age group appears to have the same characteristics as that seen in children. It is an aggressive, rapidly fatal disease with a poor response to the usual chemotherapeutic regimens for acute leukemia or poorly differentiated lymphocytic lymphoma, with which this T cell disorder is frequently grouped. An example of Burkitt's lymphoma in another young man is presented briefly to illustrate the clinical, morphologic and immunologic similarities to and differences from an aggressive B cell lymphoma.

Mesocolic lymph node histology is an important prognostic indicator for patients with carcinoma of the sigmoid colon: an immunomorphologic study.

Histologic parameters which are thought to reflect either cell-mediated (T cell) or humoral (B cell) immune responses in lymph nodes have been studied in regional lymph nodes draining carcinoma of the sigmoid colon. Patients whose lymph nodes show morphological evidence of cell-mediated immunity, manifested either by an increased number of paracortical immunoblasts or sinus histiocytosis, survive significantly longer than those whose lymph nodes show no such changes. Patients whose lymph nodes show simultaneous paracortical activity and sinus histiocytosis have the best survival of all. Of this latter group, 11/13 (83 percent) are living without signs of recurrent tumor 5 or more years after surgery. Histologic parameters which suggest an antibody-mediated immune response (germinal center activity) were not an important prognostic indicator. The occurrence of favorable lymph node histology does not appear to significantly correlate with the modified Duke's classification. Rather, the favorable changes allow selection of a large proportion of those patients within the various Duke's categories who are destined to become long-term survivors.