A look back - ipi and pembro

Here are couple of review papers looking at ipi and pembro ~

Real world treatment patterns and outcomes among metastatic cutaneous melanoma patients treated with ipilimumab. Mohr, Ascierto, Arance, et al.  J Eur Acad Dermatol Venereol. 2017 Oct 17. 

There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011.  To evaluate ipilimumab and post-ipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain following regulatory approval.  Retrospective multicentre, multinational, observational chart review study. Data were extracted from the start of ipilimumab therapy until the end of at least 40 weeks of follow-up, or death.
Data from 371 patients (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was 65 years; 62% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second-line or later therapy. Patients received on average 3.4 ipilimumab doses. The ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in Australia, 47% in Germany, 29% in Italy and 14% in Spain received another anti-melanoma treatment after ipilimumab including chemotherapy in 26% and BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received post-ipilimumab treatment showed a 40% reduced hazard of dying than those not receiving treatment after ipilimumab, after adjustment for potential confounders.

During the time observed, ipilimumab was mainly used as second-line or later therapy. A significant proportion of patients received post-ipilimumab therapy, most of which was chemotherapy. Nevertheless, overall survival following progression on ipilimumab treatment remained poor, highlighting the need for research to develop more effective end-of-life treatment options.

Sadly, yep.  We knew that.  There is also this:  

Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States: An Expanded Access Program. Gangadhar, Hwu, Postow, Hamid, Daud...O'Day, Hodi, Pavlick, et al.  J Immunother. 2017 Nov/Dec.

KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. Of the 947 evaluable patients, 621 (65.6%) remained on treatment and transitioned to receive commercial pembrolizumab following approval by the Food and Drug Administration, whereas 326 (34.4%) discontinued, most commonly for disease progression (39.6%) or death (26.4%). Objective response rate was 14.5% in the treated population (n=947) and 22.1% in patients who had greater than/= to1 response assessment reported (n=619). Twelve patients achieved complete response. One hundred eighty-one (19.1%) patients experienced greater than/= to 1 treatment-related AE, most commonly general disorders (8.0%), skin/subcutaneous tissue disorders (7.3%), and gastrointestinal disorders (6.4%); 29 (3.1%) patients experienced greater than/= to 1 grade 3/4 treatment-related AE. Immune-mediated AEs were also reported. There were no treatment-related deaths. The safety and efficacy observed in this expanded access program were consistent with those previously reported for similar populations and support the use of pembrolizumab for patients with advanced melanoma.

Remembering that this was back in the day, when in order to attain pembro, you had to have "progressed after standard-of-care therapy" (meaning ipi and BRAFi - if BRAF positive) - a circumstance which we now know provides a LESSER response to immunotherapy like pembo and nivo - Yep.  We knew this, too!!

While a look back is essential for progress and incredible strides have been made in treatments available for melanoma patients in the past 5 years,  a best case 40-50% response rate leaves far too many in need of effective therapy.  Come on researchers!!!  Ratties are counting on you.  Let's move forward....FAST! - c