PURPOSE To analyze long-term outcomes after treatment discontinuation of anti–programmed death-1 (anti–PD-1) therapy in a cohort of patients with melanoma with the longest follow-up yet available to our knowledge, including a majority of patients treated outside of a clinical trial. We also assessed efficacy of retreatment with anti–PD-1 therapy with or without ipilimumab in relapsing patients. METHODS We retrospectively analyzed all patients with nonuveal, unresectable stage III/IV melanoma treated with single-agent anti–PD-1 therapy at Memorial Sloan Kettering from 2009-2018 who had discontinued treatment and had at least 3 months of follow-up after discontinuation (n = 396). Overall survival for patients with complete response (CR) was calculated from time of CR. Time to treatment failure for patients with CR was time from CR to the next melanoma treatment or death. RESULTS CRs were seen in 102 of 396 patients (25.8%). The median number of months of treatment after CR was zero (range, stopped before CR to 26 months after CR). With a median follow-up of 21.1 months from time of CR in patients who did not relapse, the probability of being alive and not needing additional melanoma therapy at 3 years was 72.1%. There was no significant association between treatment duration and relapse risk. In multivariable analysis, CR was associated with M1b disease and cutaneous versus mucosal or acral primaries. Among the 78 patients (of 396) retreated after disease progression, response was seen in 5 of 34 retreated patients with single-agent anti–PD-1 therapy and 11 of 44 patients escalated to anti–PD-1 plus ipilimumab. CONCLUSION In our cohort, most patients discontinued treatment at the time of CR. Most CRs were durable but the probability of treatment failure was 27% at 3 years. Responses to retreatment were infrequent. The optimal duration of treatment after CR is not yet established.

SUMMARYThe Christmas Island red crab Gecarcoidea natalis undergoes extreme changes in metabolic status, ranging from inactivity during the dry season, to a spectacular annual breeding migration at the start of the wet season. The dramatic change in metabolic physiology that this polarisation entails should be reflected in changes in endocrine physiology, particularly that of the crustacean hyperglycaemic hormone (CHH), of which we know relatively little. CHH levels were measured using a novel ultrasensitive time-resolved fluoroimmunoassay (TR-FIA), together with metabolites (glucose, lactate), in the field at several scales of temporal resolution, during migratory activities (wet season) and during the inactive fossorial phase (dry season). Release patterns of CHH were measured during extreme (forced) exercise, showing for the first time an unexpectedly rapid pulsatile release of this hormone. A seasonally dependent glucose-sensitive negative-feedback loop was identified that might be important in energy mobilisation during migration. Haemolymph lactate levels were strongly correlated with CHH levels in both field and experimental animals. During migration, CHH levels were lower than during the dry season and, during migration, daytime CHH levels (when most locomotor activity occurred) increased. However, the intense dawn activity in both dry and wet seasons was not always associated with repeatable hyperglycaemia or CHH release. The results obtained are discussed in relation to the life history and behaviour of G. natalis.

9513 Background: Little is known about patients (pts) who discontinue anti-PD1 therapy after a complete response (CR) outside of clinical trials. There are also limited data about retreatment with a second course of anti-PD1 upon disease progression. Methods: We retrospectively studied pts (n = 398) at MSKCC with unresectable mel (non-uveal) who received ≥1 dose of single-agent anti-PD1 and were followed ≥3 months (mos) after treatment cessation. CR was defined radiographically or by a negative biopsy of residual tissue. Overall survival (OS) and time to treatment failure (TTF, time until next therapy or death) were calculated from time of CR. When to stop therapy and whether to retreat after progressive disease (PD) were at the discretion of the treating oncologist. A subset of pts received a second course of single-agent anti-PD1 ≥3 months after initial discontinuation; retreated pts were evaluable if they had radiographic or clinical evaluation to assess retreatment efficacy. Results: 102 pts (25.6%) achieved CR (n = 89 radiographic, n = 13 pathologic). Median follow-up was 22.6 mos for survivors who had a CR. Estimated 3-year OS from time of CR was 82.5% (95% CI 67.4-91.0). For pts who had a CR, therapy was discontinued due to CR (n = 72), toxicity (n = 24), or other reasons (n = 6). The median duration of treatment for CR pts was 9.4 mos (range 1.6-36.1). 20 CR pts later had progressive disease (PD). Median TTF has not been reached; at 3-years the estimated treatment-free survival for CR pts was 72.3% (95% CI 60.2-81.3). 34 pts received a second course of anti-PD1 for PD after a median of 11.6 mos off treatment (range 3.5-28.6). Best responses to the second course of treatment were: 2 CRs (5.9%), 3 with tumor shrinkage (8.8%), 9 (26.5%) with SD, and 20 with PD (58.8%). Of these pts who had had a CR (n = 8) or some lesser degree of tumor shrinkage (n = 13) to the initial course of anti-PD1 treatment, only 1 and 2 pts responded, respectively, to retreatment. Median duration of retreatment was 10.9 wks. Conclusions: In this largest dataset to knowledge of mel pts treated with a second course of anti-PD1, response rate was low, even in pts who had achieved a response initially. Further study is needed into the necessary duration of initial anti-PD1 treatment and optimal strategies for initial responders who discontinue and later develop PD.

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Progress in the understanding of molecular events of carcinogenesis and cancer evolution as well as the identification of tumor antigens has led to the development of different targeted therapeutic approaches, including the use of monoclonal antibodies (mAbs). Prostate cancer (PC) is highly amenable to mAb targeting given the existence of prostate-specific targets and the natural history and localization of metastatic disease. Areas covered: Several aspects of the PC phenotype, including growth factors, angiogenesis mediators, bone microenvironment signals, and immune evasion pathways, have become areas of ongoing investigation in terms of mAb targeting. These are reviewed. The greatest success so far has been the development of mAbs against prostate-specific tumor antigen (PSMA), which opened an opportunity to improve diagnostic accuracy and simultaneously target metastatic disease. Expert opinion: As mAb use in PC continues to evolve, more accurate imaging of the extent of disease and more effective mAb therapies (naked or conjugated with drugs, toxins or radioactive molecules) are emerging. In addition, the combination of mAbs with other treatment modalities is expected to further improve responses and overall survival. Identification of validated biomarkers is necessary for better recognition of patient subgroups who will derive the greatest benefit from mAb therapy.