Purpose: To study the burden and outcome of lung cancer in the elderly, particularly for patients aged 80 years and older. Patients and Methods: The national Surveillance, Epidemiology, and End Results database was analyzed for lung cancer outcomes during the period 1988 to 2003. A comparison was carried out between patients with lung cancer 80 years and older, 70 to 79 years, and younger than 70 years for demographics; stage distribution; 5-year relative survival; and survival based on histology, sex, race, stage, and treatment. The temporal trends in survival during the years 1988 to 1997 and 1998 to 2003 were also analyzed. Results: Of 316,682 patients eligible for the analysis, 45,912 (14%) were 80 years or older (ie, very elderly); 103,963 (33%) were 70 to 79 years; and 166,807 (53%) were younger than 70 years. The distribution by stage and histology was comparable for all the three groups. Overall survival rate at 5 years was lower in the very elderly (7.4% v 12.3% v 15.5%; P < .0001) across sex, histologic subtypes, stages, and racial categories. Patients aged 80 years or older were less likely to receive local therapy (no surgery or radiation) than younger patients (47% v 28% and 19% for the age subgroups ≥ 80 years, 70 to 79 years, and < 70 years, respectively). Overall outcomes for patients who underwent surgical therapy or radiation were comparable across the three age groups. In general, survival outcomes for the subgroup aged 70 to 79 years were similar to those of the subgroup aged 80 years and older who received single modality local therapy. Conclusion: Patients 80 years or older account for 14% (70 years or older accounted for 47%) of all lung cancers, are less likely to be subjected to surgery or radiation, and have inferior outcomes when compared with younger patients.

PURPOSE: Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb–mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC. PATIENTS AND METHODS: This study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary end point was safety. Secondary end points included antitumor activity by modified RECIST 1.1, overall survival, and pharmacokinetics. RESULTS: By July 19, 2022, 107 patients received tarlatamab in dose exploration (0.003 to 100 mg; n = 73) and expansion (100 mg; n = 34) cohorts. Median prior lines of anticancer therapy were 2 (range, 1-6); 49.5% received antiprogrammed death-1/programmed death ligand-1 therapy. Any-grade treatment-related adverse events occurred in 97 patients (90.7%) and grade b % 3 in 33 patients (30.8%). One patient (1%) had grade 5 pneumonitis. Cytokine release syndrome was the most common treatment-related adverse event, occurring in 56 patients (52%) including grade 3 in one patient (1%). Maximum tolerated dose was not reached. Objective response rate was 23.4% (95% CI, 15.7 to 32.5) including two complete and 23 partial responses. The median duration of response was 12.3 months (95% CI, 6.6 to 14.9). The disease control rate was 51.4% (95% CI, 41.5 to 61.2). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.1 to 5.4) and 13.2 months (95% CI, 10.5 to not reached), respectively. Exploratory analysis suggests that selecting for increased DLL3 expression can result in increased clinical benefit. CONCLUSION: In patients with heavily pretreated SCLC, tarlatamab demonstrated manageable safety with encouraging response durability. Further evaluation of this promising molecule is ongoing. [Media: see text]

Gangliosides are carbohydrate-containing sphingolipids that are widely expressed in normal tissues, making most subtypes unsuitable as targets for cancer therapy. However, the disialoganglioside GD2 subtype has limited expression in normal tissues but is overexpressed across a wide range of tumors. Disialoganglioside GD2 can be considered a tumor-associated antigen and well-suited as a target for cancer therapy. Disialoganglioside GD2 is implicated in tumor development and malignant phenotypes through enhanced cell proliferation, motility, migration, adhesion, and invasion, depending on the tumor type. This provides a rationale for targeting disialoganglioside GD2 in cancer therapy with the development of anti-GD2 monoclonal antibodies and other therapeutic approaches. Anti-GD2 monoclonal antibodies target GD2-expressing tumor cells, leading to phagocytosis and destruction by means of antibody-dependent cell-mediated cytotoxicity, lysis by complement-dependent cytotoxicity, and apoptosis and necrosis through direct induction of cell death. Anti-GD2 monoclonal antibodies may also prevent homing and adhesion of circulating malignant cells to the extracellular matrix. Disialoganglioside GD2 is highly expressed by almost all neuroblastomas, by most melanomas and retinoblastomas, and by many Ewing sarcomas and, to a more variable degree, by small cell lung cancer, gliomas, osteosarcomas, and soft tissue sarcomas. Successful treatment of disialoganglioside GD2-expressing tumors with anti-GD2 monoclonal antibodies is hindered by pharmacologic factors such as insufficient antibody affinity to mediate antibody-dependent cell-mediated cytotoxicity, inadequate penetration of antibody into the tumor microenvironment, and toxicity related to disialoganglioside GD2 expression by normal tissues such as peripheral sensory nerve fibers. Nonetheless, anti-GD2 monoclonal antibody dinutuximab (ch14.18) has been approved by the U.S. Food and Drug Administration and dinutuximab beta (ch14.18/CHO) has been approved by the European Medicines Agency for the treatment of high-risk neuroblastoma in pediatric patients. Clinical trials of anti-GD2 therapy are currently ongoing in patients with other types of disialoganglioside GD2-expressing tumors as well as neuroblastoma. In addition to anti-GD2 monoclonal antibodies, anti-GD2 therapeutic approaches include chimeric antigen receptor T-cell therapy, disialoganglioside GD2 vaccines, immunocytokines, immunotoxins, antibody–drug conjugates, radiolabeled antibodies, targeted nanoparticles, and T-cell engaging bispecific antibodies. Clinical trials should clarify further the potential of anti-GD2 therapy for disialoganglioside GD2-expressing malignant tumors.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the head and neck (ACCHN) is a rare tumor of minor salivary, parotid, and submandibular glands. The biologic behavior of the disease is poorly understood, and nonsurgical treatment strategies have yet to be standardized. The long‐term prognosis continues to be guarded, with an estimated 10‐year survival of <60%. Population‐based studies examining ACC are scarce. The authors aimed to analyze incidence rates and survival outcomes for patients diagnosed with ACCHN using national population‐based data.METHODS: Data were obtained from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Newly diagnosed ACCHN cases reported to SEER from 1973 through 2007 were categorized according to their sex, race, age, year of diagnosis, marital status, treatment interventions, primary tumor site, and disease stage. Incidence of ACCHN and postdiagnosis survival were examined over time and compared across different demographic and disease‐related categories.RESULTS: The authors identified 3026 patients with ACCHN. The mean age at diagnosis among those cases was 57.4 years (range, 11‐99 years). Analyses of incidence data demonstrated a decline in ACCHN rates between 1973 and 2007, noted across all sexes and races with no detectable inflexion points. The overall 5‐year, 10‐year, and 15‐year survival outcomes for ACCHN patients were 90.3%, 79.9%, and 69.2%, respectively. Females, patients with localized disease, and younger patients were found to have significantly better survival across all time periods (all comparison‐specific log‐rank P values <0.001). Multivariate analyses revealed better prognosis among women compared with men (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.65‐0.82), among married compared with unmarried individuals (HR, 0.81; 95% CI, 0.71‐0.91), with certain sites of origin and stage of disease (HR, 2.788; 95% CI, 2.36‐3.29), and in those who had surgery of the primary tumor site (HR, 0.45; 95% CI, 0.37‐0.54).CONCLUSIONS: The overall incidence of ACC is declining. The noted differences in survival based on sex, marital status, site of origin, and treatment intervention require further investigation. Cancer 2012. © 2012 American Cancer Society