Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma.

BACKGROUND: Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established. PATIENTS AND METHODS: This academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N = 167) or nivolumab (N = 18) in the absence of disease progression (PD) or treatment limiting toxicity (TLT) at 14 medical centres across Europe and Australia. RESULTS: Median time on treatment was 12 months (range 0.7-43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18 months (range 0.7-48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12 months (range 2-23). PD was less frequent in patients with CR (14%) compared with patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new antitumour response. CONCLUSIONS: In this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared with clinical trials. In patients obtaining a CR, and being treated for >6 months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed antitumour activity in some patients. CLINICAL TRIAL REGISTRATION: NCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970?cond=melanoma&cntry=BE&city=Jette&rank=3).

Puberty-associated gingivitis.

In a 2-yr follow-up study gingival condition was related to oral hygiene and different stages of puberty in 88 14-yr-old Finnish schoolchildren. Visible plaque and gingival bleeding after probing were determined from six teeth, at four sites each. Bitewing radiographs were taken from the molar areas. These examinations were repeated 2 yr later. The pubertal stage of the subjects was determined at the age of 14 by the school physician based on the classification of Tanner according to breast development (M) in girls and genital development (G) in boys. All subjects were in the somatic period of puberty at the time of the baseline examination. No radiographically detectable bone loss was found in either of the examinations. There was no difference in the gingival bleeding tendency at various pubertal stages when all subjects were included or when boys and girls were compared separately. Instead, a highly significant correlation was found between gingival bleeding and visible plaque, both at the baseline and 2 yr later. The results indicate that from the age of 14 to 16 the influence of oral hygiene on the gingival condition may be more important than that of the rising level of steroid hormones.

Growth of plaque while chewing sucrose and sorbitol flavoured gum.

The aim of the study was to assess the claimed toothcleansing effect of sorbitol and sucrose flavoured chewing gums. A total of 24 dental students participated in a double-blind, four times crossed over clinical trial during which each student chewed both types of gum for 4 days each. No other means to clean the teeth were allowed during the test periods. Two 4-day periods of no oral hygiene and no chewing were used as controls indicating the normal growth rate of plaque. The results confirmed earlier observations that sorbitol flavoured gum does neither increase or decrease plaque formation. Chewing of sucrose gum, however, was found to promote the growth rate of plaque. The cleansing effect of the gums was also tested on the plaque formed during the 4-day no-oral-hygiene periods. In this part of the study the chewing of 10 pieces of sorbitol flavoured gum during a time period of 3 h did not significantly reduce the plaque scores, while the sucrose flavoured gum, correspondingly used, again resulted in a statistically significant increase in the amount of bacterial deposits. Because of the rapid reaction of the plaque to sucrose flavoured gum, so-called sugarless substitutes were recommended for those who insist on chewing.