Treatment with anticancer drugs for advanced pancreatic cancer: a systematic review.

BACKGROUND: Patients with advanced pancreatic cancer have a poor prognosis and high burden of cancer-related symptoms. It is necessary to assess the trade-off of clinical benefits and possible harms of treatments with anticancer drugs (TAD). This systematic review aims to compare the effectiveness of TAD versus supportive care or no treatment, considering all patient-important outcomes. METHODS: We searched PubMed, Embase, Cochrane Library, and Epistemonikos. Two reviewers performed selection, data extraction and risk of bias assessment. We assessed certainty of the evidence using the GRADE approach. RESULTS: We included 14 randomised controlled trials. Chemotherapy may result in a slight increase in overall survival (MD: 2.97 months (95%CI 1.23, 4.70)) and fewer hospital days (MD: -6.7 (-8.3, -5.1)), however, the evidence is very uncertain about its effect on symptoms, quality of life, functional status, and adverse events. Targeted/biological therapy may result in little to no difference in overall survival and a slight increment in progression-free survival (HR: 0.83 (95%CI 0.63, 1.10)), but probably results in more adverse events (RR: 5.54 (95%CI 1.24, 23.97)). The evidence is very uncertain about the effect of immunotherapy in overall survival and functional status. CONCLUSIONS: The evidence is very uncertain about whether the benefits of using treatment with anticancer drugs outweigh their risks for patients with advanced pancreatic cancer. This uncertainty is further highlighted when considering immunotherapy or a second line of chemotherapy and thus, best supportive care would be an appropriate alternative. Future studies should assess their impact on all patient-important outcomes to inform patients in setting their goals of care.

Utilising systematic reviews to assess potential overtreatment and claim for better evidence-based research: an analysis of anticancer drugs versus supportive care in advanced esophageal cancer.

BACKGROUND: Highlighting the identified gaps in evidence-based research concerning advanced esophageal cancer (EC) treatment and care, this review evaluates the efficacy and safety of anticancer drugs compared to supportive care for advanced EC patients, aiming to assess the appropriateness of usual treatments and identify the gaps that need to be filled with primary research. METHODS: We searched (May 2022) MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Epistemonikos, and trial registries (ClinicalTrials.gov and PROSPERO) for randomised controlled trials (RCTs) comparing anticancer drugs (chemotherapy, immunotherapy, or biological/targeted therapy) with supportive care in advanced EC. The results were summarised using GRADE summary of finding tables. RESULTS: We included 15 RCTs. Most studies did not have a special focus on EC, did not detail the treatment lines in all patients, and did not evaluate all outcomes. Anticancer drugs may result in a slight increase in overall survival (OS) (HR 0.78; 95% CI 0.71, 0.86; MD 0.83 months) and better progression-free survival (PFS) (HR 0.56 95% CI 0.49, 0.64, MD 0.68 months), but also may increase toxicity (RR 1.37; 95% CI 1.13, 1.65), without a significant improvement in quality of life. The certainty of evidence was low or very low due to indirectness of results and lack of specific focus on EC in some studies. CONCLUSION: RCTs on advanced EC lack specificity, detailed treatment line information, and evaluation of all relevant outcomes. Moreover, when they find any benefit, this is negligible. Therefore, the certainty to justify anticancer drug treatments instead of supportive care in advanced EC is low or very low, and this information should be actively shared with affected patients. More and better RCTs should be conducted to assess whether any old or new proposed treatment for advanced EC patients provides a better balance of benefits and harms than the supportive care. SYSTEMATIC REVIEW REGISTRATION: The study protocol was registered in OSF ( https://doi.org/10.17605/OSF.IO/7CHX6 ) on 2022-03-29.