Purpose

At the 12th meeting of AORTIC (African Organization for Research and Training in Cancer) in Maputo, Mozambique, held between November 5 and November 8, 2019, a special workshop was organized to focus on the need for collaboration and coordination between governments and health systems in Africa with academic, industry, association, and other nongovernmental organizations to effect sustainable positive change for the care of patients with cancer.

Methods

Representatives from seven different projects in Africa presented implementation science and demonstration projects of their to date efforts in cancer system improvement including patient access, South-South partnerships, in-country specialized training, palliative care consortium, treatment outcomes, and focused pathology and diagnostic capacity building. Key partners of the various projects served as moderators and commentators during the session.

Results

From across all the presentations, lessons learned and exemplary evidence of the value of partnerships were gathered and summarized.

Conclusion

The concluding synthesis of the presentations determined that with the broad needs across cancer requiring in-depth expertise at each point on a patient's journey, no single organization can effect change alone. Multipartner collaborations not only should be the norm but should also be coordinated so that efforts are not duplicated and maximum patient access to cancer diagnosis and care is achieved.

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.7%, P = 0.006 compared to historical 1-year OS of 35%, n = 34) but was not met for sotiga/chemo (48.1%, P = 0.062, n = 36) or sotiga/nivo/chemo (41.3%, P = 0.223, n = 35). Secondary endpoints were progression-free survival, objective response rate, disease control rate, duration of response and safety. Treatment-related adverse event rates were similar across arms. Multi-omic circulating and tumor biomarker analyses identified distinct immune signatures associated with survival for nivo/chemo and sotiga/chemo. Survival after nivo/chemo correlated with a less suppressive tumor microenvironment and higher numbers of activated, antigen-experienced circulating T cells at baseline. Survival after sotiga/chemo correlated with greater intratumoral CD4 T cell infiltration and circulating differentiated CD4 T cells and antigen-presenting cells. A patient subset benefitting from sotiga/nivo/chemo was not identified. Collectively, these analyses suggest potential treatment-specific correlates of efficacy and may enable biomarker-selected patient populations in subsequent PDAC chemoimmunotherapy trials.

Identifying pan-tumor biomarkers that predict responses to immune checkpoint inhibitors (ICI) is critically needed. In the AMADEUS clinical trial (NCT03651271), patients with various advanced solid tumors were assessed for changes in intratumoral CD8 percentages and their response to ICI. Patients were grouped based on tumoral CD8 levels: those with CD8 <15% (CD8-low) received nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA4) and those with CD8 ≥15% (CD8-high) received nivolumab monotherapy. 79 patients (72 CD8-low and 7 CD8-high) were treated. The disease control rate was 25.0% (18/72; 95% CI: 15.8-35.2) in CD8-low and 14.3% (1/7; 95% CI: 1.1-43.8) in CD8-high. Tumors from 35.9% (14/39; 95% CI: 21.8-51.4) of patients converted from CD8 <15% pretreatment to ≥15% after treatment. Multiomic analyses showed that CD8-low responders had an inflammatory tumor microenvironment pretreatment, enhanced by an influx of CD8 T cells, CD4 T cells, B cells, and macrophages upon treatment. These findings reveal crucial pan-cancer immunological features for ICI response in patients with metastatic disease.