T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma.

Purpose: Gene expression analysis identifies several breast cancer subtypes. We examined the relationship of neoadjuvant chemotherapy response to outcome among these breast cancer subtypes. Experimental Design: We used immunohistochemical profiles [human epidermal growth factor receptor 2^positive (HER2+)/hormone receptor^negative for HER2+/estrogen receptorn egative (ERÀ), hormone receptor and HER2À for basal-like, hormone receptor^positive for luminal] to subtype a prospectively maintained data set of patients with breast cancer treated with neoadjuvant anthracycline-based (doxorubicin plus cyclophosphamide, AC) chemotherapy. We analyzed each subtype for clinical and pathologic response to neoadjuvant chemotherapy and examined the relationship of response to distant disease^free survival and overall survival. Results: Of the 107 patients tested, 34 (32%) were basal-like, 11 (10%) were HER2+/ERÀ, and 62 (58%) were luminal. After neoadjuvant AC, 75% received subsequent chemotherapy and all received endocrine therapy if hormone receptor^positive. The chemotherapy regimen and pretreatment stage did not differ by subtype. Clinical response to AC was higher among the HER2+/ERÀ (70 %) and basal-like (85 %) than the luminal subtypes (47 %; P < 0.0001).Pathologic complete response occurred in 36% of HER2+/ERÀ, 27% of basal-like, and 7% of luminal subtypes (P = 0.01). Despite initial chemosensitivity, patients with the basal-like and HER2+/ERÀ subtypes had worse distant disease^free survival (P = 0.04) and overall survival (P = 0.02) than those with the luminal subtypes. Regardless of subtype, only 2 of 17 patients with pathologic complete response relapsed. The worse outcome among basal-like and HER+/ ERÀ subtypes was due to higher relapse among those with residual disease (P = 0.003). Conclusions: Basal-like and HER2+/ERÀ subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers. Patients that had pathologic complete response to chemotherapy had a good prognosis regardless of subtype. The poorer prognosis of basal-like and HER2+/ERÀ breast cancers could be explained by a higher likelihood of relapse in those patients in whom pathologic complete response was not achieved.Gene expression studies have identified three major subtypes of breast cancer (basal-like, HER2+/ERÀ, and luminal; ref. 1) that have differing prognoses (2). A particularly poor outcome is seen among the two hormone receptor -negative subtypes (i.e., basal-like and HER2+/ERÀ), compared with the hormone receptor -high luminal group (2, 3). Evidence suggests that the effect of improved adjuvant chemotherapy is greater among hormone receptor -negative breast cancer (4). A recent report revealed significantly higher pathologic complete response to neoadjuvant chemotherapy among basal-like and HER2+/ERÀ subtypes compared with luminal subtypes (5). If so, this raises the question of whether the traditional perspective of pathologic complete response as a proxy for relapse and survival holds true across e...

Purpose We evaluated the combination of talimogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with advanced melanoma in a phase II study. To our knowledge, this was the first randomized trial to evaluate addition of an oncolytic virus to a checkpoint inhibitor. Methods Patients with unresectable stages IIIB to IV melanoma, with no more than one prior therapy if BRAF wild-type, no more than two prior therapies if BRAF mutant, measurable/injectable disease, and without symptomatic autoimmunity or clinically significant immunosuppression were randomly assigned 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone. Talimogene laherparepvec treatment began in week 1 (first dose, ≤ 4 mL × 10 plaque-forming units/mL; after 3 weeks, ≤ 4 mL × 10 plaque-forming units/mL every 2 weeks). Ipilimumab (3 mg/kg every 3 weeks; up to four doses) began week 1 in the ipilimumab alone arm and week 6 in the combination arm. The primary end point was objective response rate evaluated by investigators per immune-related response criteria. Results One hundred ninety-eight patients were randomly assigned to talimogene laherparepvec plus ipilimumab (n = 98), or ipilimumab alone (n = 100). Thirty-eight patients (39%) in the combination arm and 18 patients (18%) in the ipilimumab arm had an objective response (odds ratio, 2.9; 95% CI, 1.5 to 5.5; P = .002). Responses were not limited to injected lesions; visceral lesion decreases were observed in 52% of patients in the combination arm and 23% of patients in the ipilimumab arm. Frequently occurring adverse events (AEs) included fatigue (combination, 59%; ipilimumab alone, 42%), chills (combination, 53%; ipilimumab alone, 3%), and diarrhea (combination, 42%; ipilimumab alone, 35%). Incidence of grade ≥ 3 AEs was 45% and 35%, respectively. Three patients in the combination arm had fatal AEs; none were treatment related. Conclusion The study met its primary end point; the objective response rate was significantly higher with talimogene laherparepvec plus ipilimumab versus ipilimumab alone. These data indicate that the combination has greater antitumor activity without additional safety concerns versus ipilimumab.