Background:

Patients with advanced digestive non-intestinal cancers (ADNICs) have an overall poor prognosis. While guidelines commonly recommend treatment with anticancer drugs (ACDs) (i.e. chemotherapy, immunotherapy, biological/targeted therapies), their recommendations primarily focus on relative benefits in survival-related outcomes. Nevertheless, assessments of absolute survival benefits and other critical outcomes are not consistently considered.

Objectives:

To present the findings of the ‘Appropriateness of Systemic oncological Treatments for Advanced Cancer’ (ASTAC) project, a comprehensive evidence synthesis. Specifically, we aim to assess the effects of providing ACDs versus supportive care in patients with ADNICs, considering critical outcomes beyond survival.

Methods:

We conducted a comprehensive synthesis of evidence on efficacy and safety utilising a multi-pronged approach, including overviews, evidence gap maps (EGMs), and systematic reviews (SRs):
1. Overviews: We systematically searched five databases to identify existing SRs. Identified SRs were categorised by cancer location. We conducted three overviews of SRs, involving the creation of evidence matrices and de-novo meta-analyses.
2. EGMs: We complemented the previous search with a broader strategy —including randomised controlled trials (RCTs) and observational studies—, and performed three EGMs. The EGMs guided the identification of appropriate new SRs to conduct.
3. SRs: Based on the results of the EGMs, we conducted new SRs utilising the randomised controlled trials (RCTs) identified. A complementary forward citation search was conducted to ensure comprehensive coverage of relevant literature.

Results:

We conducted three overviews, three EGMs and five SRs. Overall, our analysis suggests low to very-low confidence on the effects of ACDs, showing clinically non-significant benefit in survival, with a tendency to increase toxicity. Table 1 summarises the findings.

Conclusions:

The ASTAC-Project successfully integrated various methodological approaches to synthesise evidence effectively. Current evidence to treat ADNICs with anticancer drugs is sparse, and treatments could be often considered inappropriate. Our findings should serve as a basis to promote informed shared decision-making when offering ACDs for ADNICs, aiming to prevent potential overtreatment of these patients. Moving forward, the ASTAC-Project will conduct local observational studies to assess the appropriateness of these treatments within a local context.