NYU researchers suggest a difference in the tumor progression of stage IV melanoma patients based on the initial clinical stage at original diagnosis.
The treatment of melanoma has experienced dramatic change in the last five years. Prior to 2011, there were very few standard of care options for the disease and overall survival was pretty poor, according to Melissa Wilson, M.D., Ph.D., assistant professor of medicine at the NYU Langone Medical Center.
Dr. WilsonDacarbazine, a chemotherapy medication, and an immunotherapy called IL-2 were the only standard of care options, but IL-2 was extremely toxic and only about 3% of patients responded to treatment, she says. Other chemotherapy options were being used, too, and some patients were being enrolled in clinical trials to attempt to extend life, but none of the trials had an overall survival benefit – even when the tumors shrank or symptoms improved.
“In 2011 and since then we’ve had a revolution of treatment options for patients that are providing overall survival benefits,” Dr. Wilson says. The immune checkpoint inhibitor, ipilimumab, a CTLA-4 inhibitor antibody, and PD-1 inhibitors have been approved as single agents and are now being used in combination. In addition, BRAF targeted inhibitors have been FDA approved.
The introduction of these new immunotherapies and targeted therapies have enhanced survival rates. Despite these recent advances, however, some patients with stage IV disease continue to have a poor prognosis, surviving less than a year on average.
Curious to explore the association between initial clinical stage at original diagnosis (ICS) and the overall survival (OS) following diagnosis of stage IV disease, an interdisciplinary team at the NYU Langone Medical Center that included surgeons, pathologists, medical oncologists, lab researchers and statisticians set out to learn more.
While the time to metastatic recurrence from primary melanoma diagnosis is known to vary based on the original stage at diagnosis, it has been unclear whether recurrent melanoma originating from distinct primary stages converge to similar clinical behavior once they become metastatic.
The team’s research, revealed during a poster session at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, dug into this topic and spoke to the impact of clinical stage at primary melanoma diagnosis on post-recurrence survival.1
The data utilized came from stage IV melanoma patients who were treated at NYU between 2002 and 2014. Of 388 stage IV patients studied, 97 (26%) presented at ICS-I, 101 (27%) at ICS-II, 114 (31%) at ICS-III, and 61 (16%) at ICS-IV.
“Here at NYU we’re very fortunate to have a database that allows us to keep track of all the clinical information of patients,” explains Dr. Wilson, the lead investigator. Data pertaining to aspects such as the stage of diagnosis, type of treatment received and characteristics of the tumors provides the ability to perform longitudinal studies to examine outcomes.
Significance of data
Analysis showed that patients initially diagnosed at ICS-I had longer OS than those diagnosed at ICS-II, III, or IV (mOS 1.4y, 1.1y, 1.1y, 0.9y, respectively; p = 0.03). In addition, patients who received adjuvant therapy at the time of diagnosis had significantly better OS than those who did not (mOS 2.0y vs 1.1y; p < 0.01), as did patients who received immunotherapy at the time of metastatic disease compared to those who did not, regardless of ICS (mOS 1.4y vs 0.8y; p < 0.01). No notable difference in OS was observed with targeted therapy or chemotherapy.
“Our poster does show that being diagnosed with an earlier stage melanoma, and in particular ICS-I, impacts patients’ overall survival once they develop metastatic disease,” explains Dr. Wilson, which suggests that there’s potentially a difference in the biology of these tumors that carries through once metastatic disease develops. “To our knowledge, this is the first time this has been shown,” she adds.
Although Dr. Wilson doesn’t believe these findings will spark any immediate changes for practicing physicians, she notes that the information is useful for dermatologists and medical oncologists since they lend support to the idea that enhanced screenings and early detection can improve outcomes.
“It is something that is interesting and certainly deserves further characterization and further investigation because it is still new preliminary data that needs to be further substantiated and looked at,” she says, predicting that this research will lead to additional studies.
Looking back at the tumors themselves in order to characterize them in greater detail is the logical next step, she says, but there are clear difficulties and limitations to contend with. Primary melanomas are such small samples that it’s a matter of whether or not there is enough material available to perform the experiments needed to gain additional insight.
Disclosures: Dr. Wilson reports no relevant disclosures.
1. Utter K, Rosenbaum BE, Han SW, Zhong J, Moran U, Vega-Saenz de Miera E, Darvishian F, Polsky D, Berman RS, Shapiro RL, Osman I, Pavlick AC, Wilson M. The impact of clinical stage at primary melanoma diagnosis on post-recurrence survival. Poster presented at: 2016 ASCO Annual Meeting; June 2-6; Chicago.