PET/CT scan and biopsy-driven approach for safe anti-PD-1 therapy discontinuation in patients with advanced melanoma.

BACKGROUND: Limited data exist on safe discontinuation of antiprogrammed cell death protein 1 (PD-1) therapy in responding patients with advanced melanoma. The use of 18fluorodeoxyglucose (18FDG)-PET/CT scan and tumor biopsy for assessment of active disease may be an effective predictive biomarker to guide such treatment decisions. METHODS: A retrospective study of 122 patients with advanced melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anticytotoxic T-lymphocyte-associated protein 4 combination therapy at Georgetown Lombardi Comprehensive Cancer Center was conducted. Uveal melanoma patients and those receiving concurrent experimental therapy were excluded. Baseline characteristics, treatment outcomes, and survival were analyzed. Patients who decided to come off treatment typically after 12 months using CT scan radiographic complete response (CR), 18FDG-PET/CT scan complete metabolic response (CMR) or tumor biopsy of a non-CR/CMR tumor site negative for active disease (possible pathological CR) were identified and compared with patients who discontinued treatment due to toxicity while their disease was in control. Event-free survival (EFS) was assessed from the last dose of anti-PD-1 therapy to progression requiring subsequent treatment (surgery, radiation, and/or systemic therapy) or referral to hospice/death due to melanoma. RESULTS: 24 (20%) patients discontinued treatment by choice with no active disease and 28 (23%) patients discontinued treatment due to toxicity with disease control after 12-month and 4-month median treatment durations, respectively. Similar baseline characteristics were observed between cohorts except higher prior receipt of ipilimumab (29% vs 7%; p=0.036) and fewer BRAF mutant positive disease (17% vs 41%; p=0.064) in patients off treatment by choice. Three-year EFS rates were 95% and 71%, respectively. No significant associations between EFS and sex, disease stage, lactate dehydrogenase elevation, BRAF status, prior systemic therapy, ECOG performance status, presence of brain metastases, or combination versus monotherapy were observed. Tumor biopsies led to alternative management in 3/10 patients due to active metastatic melanoma or second malignancy. CONCLUSIONS: Anti-PD-1 therapy discontinuation after 12 months when no active disease is observed on CT scan, PET/CT scan or tumor biopsy may have low rates of disease relapse in patients with advanced melanoma. Biopsy of residual disease may frequently lead to a change in management. These findings are undergoing validation in the EA6192 trial.

Implementation of the Smoking Treatment and Recovery (STAR) program: healthy cancer survivorship through integrated tobacco control.

PURPOSE: It is well-established that persistent tobacco use among patients with cancer results in numerous adverse outcomes. However, the assessment and treatment of tobacco use with evidence-based methods have been lacking in cancer care. Our cancer center has established its first tobacco treatment program, a multidisciplinary, evidence-based, clinical program for hematology/oncology patients. METHODS: We describe the development and implementation of the program, emphasizing lessons learned in treating nicotine addiction among patients who are at very high risk for continuing to use tobacco throughout the survivorship phase. RESULTS: We developed a system to assess tobacco use at each outpatient visit, from those recently diagnosed to long-term survivors. For patients who have smoked in the past month, the protocol offers standard behavioral and pharmacological treatments, delivered by tobacco treatment specialists and nurse practitioners over four in-person and/or telephone-based sessions. Partnerships with the Psychosocial Oncology and Cancer Survivorship Programs have provided integrated and comprehensive care for patients during and after their cancer treatment. CONCLUSIONS: The systematic efforts to reach and engage current smokers have laid the groundwork for maximizing the program's future effectiveness and impact. Our initial results demonstrate not only the complexities but also the feasibility of developing a new tobacco treatment program in the oncology setting. IMPLICATIONS FOR CANCER SURVIVORS: The implications for cancer survivors are the significant improvements in treatment outcomes that occur with tobacco abstinence.