Analysis of almost 2,000 patients receiving treatment with metastatic melanoma , targeted (target) therapy or immunotherapy, showed that patients who were classified as obese patients, ie. who had a body mass index (BMI) of 30 or more, the survival rate was significantly higher than that of patients who had normal weight. But this conclusion only applies to male patients - women no such law was found.
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"Obese people consistently treated better than men with a normal BMI, and the total was almost vyivaemost vdoe more," - said the study's lead author Jennifer MakKuad, MD . In the comparison of survival of female patients with normal and overweight were no significant differences.
Conclusion is based on the analysis of the six groups, bolee1900 patients. Treatment regimens differed among the groups were the following:
- Targeted therapy of melanoma in Israel with inhibitors of BRAF / MEK
- immunotherapy of melanoma in Israel
- chemotherapy of melanoma in Israel
Superior, long-term responses were observed in patients with metastatic melanoma stage 4, treatment was carried out focused (targeted) therapy and immunotherapy, but not with cytotoxic chemotherapy.
The study was published online on February 12 in Lancet Oncology.
Similar observations have been made in studies of other cancers, he noted in an accompanying commentary by Andrew J.. Hayes, MBBS, PhD, and James Larkin, MD, of the Royal Center for National Health System Marsden, London, UK.
Observational studies in several tumor types have shown that there is a connection honey moderately increased BMI and improved results during treatment and during follow-up periods. "However, this protective effect is almost completely leveled as uvelichiny body mass index to morbidly obese level. It izmenenenie called obesity paradox "- note the editors.
Unlike these previous studies, in this study, patients diagnosed with melanoma metastases, "there is a linear relationship between povyeniem efektivnosti treatment and an increase in BMI in male patients. This correlation was true to the morbidly obese BMI level ", - said Hayes and Larkin. This reinforces the idea that there might be a basic biological mechanism, they added.
Previous studies have found that obesity is associated with increased risk of melanoma in men, and in a large group of patients who underwent surgical treatment of melanoma , a higher BMI is associated with worse outcomes. Based on these data, the researchers hypothesized that obesity is associated with worse outcomes in patients with metastatic melanoma, which will be assigned to the treatment of melanoma with modern biological methods. But what they vyvili was completely the opposite.
For their study, the researchers collected data from six clinical groups of patients with metastatic melanoma who were treated with three types of approved therapies - targeted therapy (BRAF / MEK inhibitors), immunotherapy or chemotherapy (two groups).
For each group, researchers evaluated the relationship between BMI and clinical outcome (PFS [PFS] and overall survival [RH]). Kaplan-Meier curves PFS and OS were generated by BMI category and sex.
Any model that shows the relationship between BMI and survival was adjusted for prognostic factors, including age, disease status, LDH status and performance metrics.
Two of the six groups were treated with targeted drugs and dabrafenib trametinib (n = 599) or vemurafenib and cobimetinib (n = 240); two (n = 320 and n = 221) leili dacarbazine; alone (n = 207) treated with combination immunotherapy dacarbazine and ipilimumab; and one (n = 331) was treated melanoma immune drugs (pembrolizumab, nivolumab or atezolimumab).
In all six groups 36% of patients had normal weight (BMI 18.5 - 24.9), 37% were overweight (BMI 25.0 - 29.9), and 27% were obese (BMI ≥30).
In the group treated with dabrafenib and trametinib, the median PFS for patients with a normal BMI was 9.6 months, and median overall survival - 19.8 months. However, obese patients, the median PFS was 15.7 months, and median overall survival - 33.0 months.
It was shown that the difference in survival of patients with normal weight and obese patients was statistically significant only for the OS and for men only. Median overall survival in men with normal weight was 16.0 months versus 36.5 months for obese men.
The difference in survival without relapse was significantly longer. The median PFS for men with normal weight was 7.4 months versus 12.8 months for obese men. The researchers also analyzed the BMI as a continuous variable. In this analysis, there was related to the level of an inverse relationship between BMI and CAP when BMI levels passed in morbid obesity.
In contrast, women with a normal BMI, median PFS was 14.5 months, compared with a median PFS , equal to 17.1 months for women with obesity. Median survival was at least 33 months for women with normal BMI, and women with obesity.
Similar associations were observed in the group who received vemurafenib plus cobimetinib, ipilimumab plus dacarbazine and pembrolizumab, nivolumab or atezolimumab.
However, there was found no positive effect on obesity PFS and OS in the two groups that were mono treatment of melanoma chemotherapy (dacarbazine).
MakKuade and colleagues noted that in their study, the effect of moderate levels of BMI with improved outcomes for patients with overweight and strong consistent survival advantage in patients with obesity indicate an underlying biological mechanism.
The researchers suggest that sexual identity can indicate a potential hormonal mediator. "Adipose tissue produces an enzyme called aromatase, which converts male hormones, called androgens in female hormones - estrogens. Perhaps this is the basis of the fact that obese patients achieve better survival, "- said in a statement MakKuade.
The researchers are collaborating with researchers from the University of Pennsylvania have discovered that the inclusion of a very specific type of estrogen receptor in melanoma cells makes them susceptible to immunotherapy.
In his editorial Hayes and Larkin noted that, given the compelling evidence that obesity is a major risk factor for death and cancer, these results should not be extrapolated. These results are applicable only to male patients with a single tumor type, which are specific types of cancer treatment or targeted immune therapy and the relationship between obesity and cancer is complex.
"However, some patients with overweight with melanoma, which are under active treatment, can be assured that it is often cited negative association of obesity with the results of cancer treatment does not belong to him at this time," - they say.
Makkuad agreed. "Report on the public health - is not that obesity - it's good. Obesity is a proven risk factor for many diseases ", - she said. "Even within our observation group, we should not assume that patients, to improve the results of treatment of melanoma with metastases should deliberately gain weight. We need to find out what is this paradox, and learn how to use this information for all of our patients, "- she added.
Source: MedscapeMedical News