ASCO 2017: I-SPY 2 Trial: Combination of Pembrolizumab Plus Standard Neoadjuvant Therapy in High-Risk Breast Cancer


“At the 2017 ASCO Annual Meeting, results were presented from the phase II I-SPY 2 trial investigating pembrolizumab (Keytruda) in combination with standard therapy (paclitaxel followed by doxorubicin and cyclophosphamide) as a neoadjuvant treatment for patients with locally advanced triple-negative breast cancer or hormone receptor–positive/HER2-negative breast cancer (Abstract 506).

“Findings showed that the addition of pembrolizumab increased the estimated pathologic complete response rate nearly threefold in patients with triple-negative breast cancer (60% vs 20%) and in patients with hormone receptor–positive/HER2-negative breast cancer (34% vs 13%) compared to standard therapy. Overall, based on Bayesian predictive probability of success in a confirmatory phase III trial, pembrolizumab has graduated from the I-SPY 2 TRIAL for all signatures in which it was tested (triple-negative breast cancer, all HER2-negative, and hormone receptor–positive/HER2-negative).”

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Rolapitant Reduced Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy or Anthracycline/Cyclophosphamide

“In a phase III study reported in The Lancet Oncology, Schwartzberg et al found that the addition of rolapitant to serotonin (5-HT3) receptor antagonist and dexamethasone treatment significantly improved complete response rates in prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens.

“In this double-blind trial, patients from 170 sites in 23 countries were randomly assigned between March 2012 and September 2013 to receive oral rolapitant 180 mg or placebo 1 to 2 hours before the administration of moderately emetogenic chemotherapy. All patients received oral granisetron 2 mg and oral dexamethasone 20 mg on day 1 (except for those receiving taxanes, who received dexamethasone according to the package insert) and granisetron 2 mg on days 2 and 3. Treatment was given for up to six cycles, with a minimum of 14 days…

“The investigators concluded: ‘Rolapitant in combination with a 5-HT3 receptor antagonist and dexamethasone is well tolerated and shows superiority over active control for the prevention of chemotherapy-induced nausea and vomiting during the 5-day (0–120 h) at-risk period after administration of moderately emetogenic chemotherapy or regimens containing an anthracycline and cyclophosphamide.’ “

MM-302 Shows Promise in Heavily Pretreated HER2-Positive Breast Cancer

“A phase I study of MM-302, an antibody-drug conjugated human epidermal growth factor receptor 2 (HER2)-targeted liposomal doxorubicin, as a monotherapy or in combination with trastuzumab or trastuzumab and cyclophosphamide had a manageable safety profile and encouraging efficacy results in a group of heavily pretreated women with HER2-positive metastatic breast cancer.

“The results of the study were presented by Patricia LoRusso, DO, professor of medicine in the division of oncology at Yale University in New Haven, Connecticut, at the American Association for Cancer Research (AACR) Annual Meeting.

“Patients in the study who received at least 30 mg/m2 of MM-302 plus trastuzumab had a median progression-free survival of 7.6 months (95% confidence interval [CI], 3.6–10.9); those treated with the addition of cyclophosphamide had a median progression-free survival of 10.6 months (95% CI, 1.8–10.6).

“ ‘We are encouraged by these data on the safety and promising clinical activity of MM-302 in patients who have exhausted many therapeutic options for their disease. Our results support the further evaluation of MM-302 in an anthracycline-naive population in the HERMIONE trial,’ said LoRusso in a prepared statement.”

Four Cycles of FEC Chemotherapy Are as Good as Six Cycles in Node-Negative Breast Cancer

The gist: A recent clinical trial showed that people with node-negative breast cancer did just as well on a shorter, four-week chemotherapy treatment as people who took a longer, six-week one. The shorter treatment consisted of four cycles of doxorubicin and cyclophosphamide. The longer one involved six cycles of 5-fluorouracil, epirubicin and cyclophosphamide. Patients in both groups had similar survival rates, and people in the longer treatment group had worse side effects.

“Patients with node-negative breast cancer who received six cycles of 5-fluorouracil, epirubicin and cyclophosphamide experienced similar DFS and OS as patients who received four cycles of doxorubicin and cyclophosphamide, according to results of a phase 3 study presented at the San Antonio Breast Cancer Symposium.

“ ‘[In the MA-5 trial, the NCIC Clinical Trials Group] administered a dose-intensified epirubicin program, and the RFS and OS results were encouraging,’ Charles Edward Geyer, Jr., MD, FACP, associate director for clinical research at Virginia Commonwealth University Massey Cancer Center, said during his presentation. ‘Additionally, the French Adjuvant Study Group around that time had also evaluated their standard adjuvant regimen of FEC-50 and had shown that six cycles of therapy were more effective than three. So, at that time, we had two separate trials looking at different epirubicin schedules, both of which had seemed to be positive. It seemed reasonable at that time to compare [doxorubicin and cyclophosphamide] with one of those regimens. Since we were going to conclude the study in node-negative patients and include post-menopausal women, we chose the FEC-100 [chemotherapy regimen] because of its improved toxicity profile…’

“ ‘[Six cycles of] FEC-100 did not improve the primary endpoint of DFS or our secondary endpoint of OS relative to [four cycles of] AC,’ Geyer said. ‘Toxicities were increased with the FEC-100, which wasn’t unexpected because it did administer additional cycles of therapy compared with AC. Overall, the results do not support the use of six cycles of anthracycline-based regimens in node-negative breast cancer.’ “

Adjuvant Paclitaxel Not Equivalent to Doxorubicin/Cyclophosphamide in Breast Cancer With 0 to 3 Positive Axillary Nodes

“In the phase III Cancer and Leukemia Group B (CALGB) 40101/Alliance trial reported in the Journal of Clinical Oncology, Shulman et al found that noninferiority of adjuvant single-agent paclitaxel was not established vs doxorubicin/cyclophosphamide for relapse-free survival in women with operable breast cancer with 0 to 3 positive nodes. Paclitaxel was less toxic than doxorubicin/cyclophosphamide.”

Editor’s note: A recent study found that treatment with the drug paclitaxel was no better than a combination of doxorubicin and cyclophosphamide for breast cancer patients who had 0-3 positive axillary nodes (i.e. cancer cells were found in 0-3 lymph nodes; cancer cells in lymph nodes can be used to predict the risk of metastatic breast cancer).

Major Cancer Regressions in Mesothelioma After Treatment with an Anti-Mesothelin Immunotoxin and Immune Suppression

We describe the results of a trial in which major antitumor responses were seen in patients with advanced mesothelioma who received the anti-mesothelin immunotoxin SS1P, together with pentostatin and cyclophosphamide, to deplete T and B cells. Of 10 patients with chemotherapy-refractory mesothelioma, 3 have had major tumor regressions with 2 ongoing at 15 months, and 2 others responded to chemotherapy after discontinuing immunotoxin therapy. Antibody formation was markedly delayed, allowing more SS1P cycles to be given, but this alone does not appear to account for the marked antitumor activity observed.