What to do when that one melanoma tumor keeps growing?

For some melanoma patients, despite a pretty good response to targeted or immunotherapy, there remains that single lesion or one group of tumors that just won't respond!!!  What are they to do with that???  Localized treatment is becoming more clearly the answer!  This article noted the benefit of local surgery to excise the problem child:  When in doubt, cut it out!!!  Now there's this:

The Management of Oligoprogression in the Landscape of New Therapies for Metastatic Melanoma.  Guida, Bartolomeo, De Risi, et al.  Cancers (Basel). 2019 Oct 14. 

Background: A limited degree of progression after a response to treatment is labelled as oligoprogression and is a hot topic of metastatic melanoma (MM) management. Rogue progressive metastases could benefit from local treatment, which could allow the continuation of ongoing systemic therapy, also known as treatment beyond progression (TBP). 

Methods: We retrospectively reviewed 214 selected MM patients who developed oligoprogression during treatment with v-Raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen-activated-extracellular signal-regulated kinase (MEK) or programmed cell death protein 1 (PD-1) inhibitors and received a local treatment continuing TBP. We performed univariate and multivariable analyses to assess the association between therapy outcomes and a series of clinical and biological features. 

Results: We identified 27 (10%) oligoprogressed patients treated locally with surgery (14), radiosurgery (11), and electrochemotherapy (2). TBP included PD-1 inhibitors (13) and BRAF/MEK inhibitors (14). The median progression-free survival post oligoprogression (PFSPO) was 14 months (5-19). In the univariate analysis, a significantly longer PFSPO was associated with complete response (CR), Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, neutrophils/lymphocytes ratio (N/L) less than 2, and progression-free survival (PFS) at oligoprogression greater than 11 months. Nevertheless, in the multivariable analysis, only CR and N/L less than 2 were found to be associated with longer PFSPO. 

Conclusions: In selected patients, local treatments contribute to controlling oligoprogression for a long time, allowing the continuation of systemic treatment and prolongation of overall survival (OS). Increasing biological and clinical knowledge is improving the accuracy in identifying patients to apply for local ablative therapies.

So these researchers looked back on the records of 214 melanoma patients who developed oligoprogression.  They found 27, 13 of whom were treated with PD-1 inhibitors and 14 who were treated with BRAF/MEK.  Those patients then had their local non-responding lesions treated with either surgery (14), radiation (11), electrochemotherapy (2).  Average progression free survival after those therapies was 14 months.  Only complete response and a NLR less than 2 were factors that were significantly associated with a longer progression free survival after that treatment.

The article below, further corroborates the need for - and good responses from - localized treatment in patients who experience limited progression after treatment with checkpoint inhibitors:

Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma.  Klemen, Wang, Feingold, et al.   J Immunother Cancer. 2019 Jul 24.

Checkpoint inhibitors (CPI) have revolutionized the treatment of metastatic melanoma, but most patients treated with CPI eventually develop progressive disease. Local therapy including surgery, ablation or stereotactic body radiotherapy (SBRT) may be useful to manage limited progression, but criteria for patient selection have not been established. Previous work has suggested progression-free survival (PFS) after local therapy is associated with patterns of immunotherapy failure, but this has not been studied in patients treated with CPI.

We analyzed clinical data from patients with metastatic melanoma who were treated with antibodies against CTLA-4, PD-1 or PD-L1, either as single-agent or combination therapy, and identified those who had disease progression in 1 to 3 sites managed with local therapy. Patterns of CPI failure were designated by independent radiological review as growth of established metastases or appearance of new metastases. Local therapy for diagnosis, palliation or CNS metastases was excluded.

Four hundred twenty-eight patients with metastatic melanoma received treatment with CPI from 2007 to 2018. Seventy-seven have ongoing complete responses while 69 died within 6 months of starting CPI; of the remaining 282 patients, 52 (18%) were treated with local therapy meeting our inclusion criteria. Local therapy to achieve no evidence of disease (NED) was associated with three-year progression-free survival (PFS) of 31% and five-year disease-specific survival (DSS) of 60%. Stratified by patterns of failure, patients with progression in established tumors had three-year PFS of 70%, while those with new metastases had three-year PFS of 6%. Five-year DSS after local therapy was 93% versus 31%, respectively.

Local therapy for oligoprogression after CPI can result in durable PFS in selected patients. We observed that patterns of failure seen during or after CPI treatment are strongly associated with PFS after local therapy, and may represent a useful criterion for patient selection. This experience suggests there may be an increased role for local therapy in patients being treated with immunotherapy.

Though not listed in either of these articles, I would submit that intralesional therapy (if the lesion in question is accessible) as another good option to use in getting rid of a pesky melanoma remnant!  Wishing all of you my best! - c