Abstracts of Interest From the 2012 American Society of Clinical Oncology Annual Meeting

Antipsychotic Controls Breakthrough Nausea and Vomiting

Patients with chemotherapy-induced nausea and vomiting (CINV) that persists in spite of recommended prophylaxis may be helped by the antipsychotic medication olanzapine. In a double-blind randomized trial of patients with breakthrough CINV after highly emetogenic chemotherapy, 71% of patients given olanzapine 10 mg orally for 3 days had no further vomiting, compared with 32% who received metoclopramide 10 mg orally 3 times a day for 3 days, and 67% versus 24% had no further nausea. Navari RM, et al. Abstract 9064.

Glucocorticoid, Ginseng Reduce Cancer-Related Fatigue

The use of dexamethasone for up to 15 days reduced cancer-related fatigue more effectively than placebo among patients with advanced cancer. The study randomly assigned 132 patients with documented fatigue to 4 mg dexamethasone twice a day or placebo for 14 days. On day 15, the dexamethasone group demonstrated significant improvements on measurements of fatigue, symptom distress, physical symptoms, and quality of life, while the placebo group did not improve over baseline. In a separate randomized study of 364 patients with fatigue, 8 weeks of ginseng (2000 mg ground Wisconsin ginseng root) also significantly improved fatigue scores, especially among patients currently on treatment. Yennurajalingam S, et al. Abstract 9002; Barton DL, et al. Abstract 9001.

Primary Care Providers Largely Unaware of Chemotherapy’s Late Effects

A survey of primary care providers (PCPs) showed an alarming level of ignorance about the late effects of common chemotherapy regimens for common cancers. The 2009 Survey of Physician Attitudes Regarding the Care of Cancer Survivors involved 1072 PCPs and 1130 oncologists. Physicians were asked to select which of 5 late effects of 4 widely used breast and colorectal cancer drugs (doxorubicin, paclitaxel, oxaliplatin, and cyclophosphamide) they observed most often in their practices, or had seen reported. Among the PCPs, only 15% to 55% identified the common side effects with the drugs. While oncologists were much better—with 62% to 97% answering correctly—there was still some room for improvement, the authors suggested. Nakhlyudov L, et al. Abstract 6008.

T-DM1 Prolongs Remission in Metastatic Breast Cancer

Trastuzumab emtansine (T-DM1), the antibody-drug conjugate linking trastuzumab to a cytotoxic agent, significantly prolonged disease-free survival in previously treated metastatic breast cancer in the international phase 3 EMILIA trial. Compared with a standard regimen, T-DM1 reduced the risk of disease progression by 35%, improving progression-free survival (PFS) from 6.4 to 9.6 months (P <.0001). Overall survival (OS) was numerically improved though the difference is not yet statistically significant. T-DM1 was also substantially better tolerated. Blackwell K, et al. LBA1.

Intermittent Androgen-Deprivation Therapy Should Not Replace Continuous Treatment in Prostate Cancer

Continuous androgen-deprivation therapy should remain the standard of care for the treatment of men with hormone- sensitive metastatic prostate cancer, according to the results of the phase 3 international SWOG 9346 trial. The 17-year study treated 3040 newly diagnosed patients with gose - rlin and bicalutamide for 7 months. Those who achieved PSA ≤4 ng/mL were randomly assigned to continuous treatment or intermittent treatment upon signs of progression. The intermittent approach was “not shown to be non-inferior to” continuous treatment. Median OS was 5.8 years with continuous therapy and 5.1 years with intermittent therapy, and 7-year survival was 42% and 38%, respectively. Hussain M, et al. Abstract 4.

Androgen Blockers Score Big in Prostate Cancer

For the treatment of metastatic castration- resistant prostate cancer (CRPC), 2 drugs targeting the androgen receptor returned impressive results. In men who had not been treated yet with chemotherapy, abiraterone significantly improved radiographic PFS in the phase 3 COUAA- 302 trial. Median PFS was 8.3 months with placebo, but has not been reached in the abiraterone group. The drug is currently approved for patients previously treated with chemotherapy, but these data suggest it would be effective earlier in the disease. The phase 3 AFFIRM trial of a similar drug, enzalutamide, in 1199 CRPC patients with prior docetaxel treatment, found a 4.8-month OS improvement, and a 5.4-month improvement in PFS (P <.0001). Ryan CJ, et al. LBA4518; de Bono JS, et al. Abstract 4519.

PD-1 Targeted Immune Therapy Active in Solid Tumors

In a phase 1 trial, the investigational drug BMS-936558 caused tumor shrinkage in about one-quarter of 296 patients with advanced melanoma (28% response rate), renal cancer (27%), and non–small cell lung cancer (18%). The antibody drug targets a key pathway in T cells called PD-1, which inhibits the body’s immune response to cancer. By blocking this pathway, BMS- 936558 may reactivate the immune system to attack the tumor. A subanalysis of the data hinted at a potential biomarker, a protein called PD-L1. One-third of patients expressing PD-L1 responded to this novel therapy. Topalian SL, et al. Abstract CRA2509.

Crizotinib Effective in Pediatric Cancers

Crizotinib, already proven effective in non–small cell lung cancer patients with ALK gene abnormalities, shows promise for the treatment of anaplastic large cell lymphoma (ALCL), inflammatory myofibroblastic tumors, and aggressive forms of neuroblastoma in children, according to a study of 70 children whose cancer was refractory to standard therapies. The greatest activity, an 88% response rate, was for ALCL, though complete responses were observed in all 3 tumor types. Responders have remained on therapy for up to 2 years without progression. Mosse YP, et al. Abstract 9500.

Afatinib Delays Progression in Lung Cancer

In the phase 3 LUX-Lung 3 trial of 345 patients with advanced non–small cell lung cancer of adenoma histology harboring the epidermal growth factor receptor (EGFR) mutation, singleagent treatment with the oral EGFR inhibitor afatinib delayed disease progression by more than 4 months over a relatively new first-line regimen, pemetrexed and cisplatin. Median PFS was 11.1 months with afatinib versus 6.9 months with standard therapy, a 42% reduction in risk (P = .0004). More strikingly, in patients with 2 common mutations, afatinib doubled the time in remission, from 6.9 months to 13.6 months (P <.0001). Afatinib blocks the EGFR pathway more thoroughly and permanently than current EGFRtargeted treatments, and also blocks the broader ErbB family of receptors. Yang J C-H, et al. LBA7500.

Regorafenib Fills Unmet Needs in GI Tumors

In both colorectal cancer and gastrointestinal stromal tumors (GIST) refractory to current therapies, the oral multikinase inhibitor regorafenib improved outcomes in phase 3 trials. In the CORRECT trial of 770 advanced colorectal cancer patients, OS was improved by 29% with regorafenib, versus placebo, from 5.0 to 6.4 months (P = .0052). In the study of 199 patients with GIST, regorafenib improved PFS from 0.9 months with placebo to 4.8 months, a 73% reduction in risk (P <.0001). Side effects were in line with other tyrosine kinase inhibitors. Van Cutsem E, et al. Abstract 3502; Demetri GD, et al. LBA10008.

In Breast Cancer, Older Drug Wins Out

In a phase 3 randomized trial of 799 patients, 2 newer and significantly more expensive drugs—nab-paclitaxel and ixabepilone—were not superior to standard weekly treatment with paclitaxel as first-line treatment for advanced breast cancer (most patients also received bevacizumab). Median PFS was 10.6 months for the paclitaxel arm, 9.2 months for nab-paclitaxel, and 7.6 months for ixabepilone. Weekly ixabepilone was significantly less effective than paclitaxel, and nab-paclitaxel was not superior to it. Grade 3 or 4 hematologic and nonhematologic toxicities were also lowest with paclitaxel, including peripheral neuropathy (16% vs 25% with either experimental arm). The authors suggested that nab-paclitaxel be reserved for patients with sensitivity reactions to paclitaxel and those for whom corticosteroids are not ad - vised. Rugo H, et al. CRA1002.

Melanoma Treatment Options Further Expand

Patients with advanced melanoma who harbor the BRAF mutation may soon have treatment options beyond vemurafenib. In two phase 3 studies (METRIC and BREAK-3), the investigational BRAF inhibitor dabrafenib and the first-in-class MEK inhibitor trametinib, as single agents, essentially doubled the median PFS, compared with chemo therapy treatment (P <.0001 for both). But when the 2 were combined in an open-label phase 1/2 dose-finding study, the results were even better. Median PFS reached 7.4 months, and rose to 10.8 months among patients who were optimally dosed. Importantly, the combination was associated with less skin toxicity (14%) than is observed with vemurafenib alone. Hauschild A, et al. LBA8500; Robert C, et al. LBA8509; Weber JS, et al. Abstract 8510.

For Metastatic Kidney Cancer, Patients Prefer Pazopanib

In a study with a novel aim and design, patients with metastatic renal cell carcinoma were treated with 2 approved agents, then asked which treatment they preferred. Almost 50% more patients preferred pazopanib over sunitinib, citing less fatigue and better quality of life with this agent (the study did not evaluate efficacy). The PISCES study enrolled 169 patients assigned to one agent for 10 weeks, and to the other for 10 weeks after a 2-week washout period. At 22 weeks, 70% preferred pazopanib, 22% preferred sunitinib, and 8% had no preference (P <.001). Physicians also preferred pazopanib (61%) over sunitinib (22%) while 17% had no preference. Escudier BJ, et al. Abstract CRA4502.