ABSTRACT
PURPOSE: Immune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART). PATIENTS AND METHODS: We performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity. RESULTS: Thirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events. CONCLUSIONS: Ipilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , CTLA-4 Antigen/antagonists & inhibitors , Neuroendocrine Tumors/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Rare Diseases/drug therapy , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Ipilimumab/administration & dosage , Male , Middle Aged , Neuroendocrine Tumors/pathology , Nivolumab/administration & dosage , Prognosis , Prospective Studies , Rare Diseases/pathology , Survival RateABSTRACT
PURPOSE: Positron emission tomography (PET) is widely used for the staging evaluation of non-small-cell lung cancer; however, its use in small-cell lung cancer (SCLC) remains investigational. PATIENTS AND METHODS: We did a retrospective study of 137 patients to evaluate the role of PET in SCLC. Fifty-one of 137 patients had computed tomography (CT) and PET scans during initial evaluation of a lung mass. RESULTS: All 51 patients had PET-positive results for malignancy (100% sensitivity). In 40 of 51 cases (78%), the PET staging correlated with that on CT. Two of 51 patients (4%) had disease that was accurately upstaged by PET. Positron emission tomography accurately downstaged disease in 6 of 51 patients (12%). Positron emission tomography detected additional sites of disease in 13 of 42 patients (32%). Of the 13 additional sites of disease, PET detected supraclavicular nodes in 4 of 13 patients (30%) and bone lesions in 4 of 13 patients (30%). The sensitivity to detect brain lesions was 5 of 11 patients (45%) in this series. In this series, the PET results from 8 of 51 patients (16%) resulted in a change in disease management. Because of PET results, 6 of 51 patients (12%) who otherwise would not have been treated, were treated with radiation. CONCLUSION: Positron emission tomography is potentially useful for accurate initial staging of SCLC and can ensure that a patient's disease is not overstaged by CT scan, which might result in denied potentially curative treatment for limited-stage SCLC. It can identify the occult adrenal metastasis and metastasis to supraclavicular lymph nodes that are missed by CT; however, brain lesions are difficult to assess by PET.