A 77-year-old patient treated with ipilimumab (anti-CTLA-4 antibody) for metastatic melanoma developed autoimmune pancytopenia (anemia, thrombocytopenia, and neutropenia) 8 days after the fourth infusion. This pancytopenia was resistant to high-dose oral corticosteroids (1 mg/kg) and to hematopoietic growth factors. It resolved after intravenous immunoglobulins injection. To date, only 1 case of autoimmune pancytopenia has been reported after this treatment. According to the case that we report, it seems essential to control the leukocyte count before any injection of ipilimumab.

Background: Randomized clinical trials (RCTs) of anticancer drugs without active comparators in patients who have exhausted standard of care treatment options are debated. We aimed to quantify the safety and the efficacy of anticancer drugs in advanced cancer patients who have exhausted standard of care treatments from RCTs without active comparators. Methods: This systematic review and meta-analysis was conducted according to preferred reporting Items for systematic review and Meta-Analyses (PRISMA) guidelines (CRD42021243968). A systematic literature search of English language publications from January 1, 2000, to January 7, 2021, was performed using MEDLINE (PubMed). Eligible trials included all RCTs evaluating anticancer drugs in adult patients with advanced solid tumors with a control arm without any anticancer drug consisting of best supportive care with or without a placebo. RCTs performed in the adjuvant, neoadjuvant or maintenance settings were excluded, as were clinical trials evaluating anticancer drugs in combination with radiotherapy. Two authors (C.M.B. and E.C.) independently reviewed the studies for inclusion. Data from published reports were extracted by investigators, and random-effects meta-analysis was performed to estimate the overall hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS). Correlations between severe toxicity and efficacy was assessed using R² measures. Findings: Of 3551 studies screened, 128 eligible trials were found involving 47,432 patients. The HRs for PFS and OS were 0·58 [95%CI: 0·53–0·63] and 0·82 [95%CI: 0·78–0·85]. The absolute benefits however were limited with PFS and OS gains of 2·1 and 0·5 months. The absolute excesses in all grade, severe grade III, IV and V (death) adverse events between the two arms were +13·9%, 10·2%, and +0·5%. A weak correlation was measured between the excess of severe toxicity and efficacy (all R² < 0·2). Interpretation: Anticancer drugs evaluated in RCTs against no active treatment benefited trial participants. Severe toxicity did not significantly correlate with efficacy. None.

Precision oncology is currently based on pairing molecularly targeted agents (MTA) to predefined single driver genes or biomarkers. Each tumor harbors a combination of a large number of potential genetic alterations of multiple driver genes in a complex system that limits the potential of this approach. We have developed an artificial intelligence (AI)-assisted computational method, the digital drug-assignment (DDA) system, to prioritize potential MTAs for each cancer patient based on the complex individual molecular profile of their tumor. We analyzed the clinical benefit of the DDA system on the molecular and clinical outcome data of patients treated in the SHIVA01 precision oncology clinical trial with MTAs matched to individual genetic alterations or biomarkers of their tumor. We found that the DDA score assigned to MTAs was significantly higher in patients experiencing disease control than in patients with progressive disease (1523 versus 580, P = 0.037). The median PFS was also significantly longer in patients receiving MTAs with high (1000+ <) than with low (<0) DDA scores (3.95 versus 1.95 months, P = 0.044). Our results indicate that AI-based systems, like DDA, are promising new tools for oncologists to improve the clinical benefit of precision oncology.

Over the past 20 years, several innovative therapies have been implemented in the treatment of lung cancer that have had reported survival benefits in clinical trials. Whether these improvements translate into the clinic setting has not been studied yet. We retrospectively analyzed all patients consecutively treated at Institute Curie for metastatic lung cancer. Diagnosis date was used to define three periods, based on the approvals of novel treatment strategies in the first-line setting, including targeted therapies in 2010 and immunotherapy in 2018. Endpoints included Overall survival (OS), survival rate of 2 years and 5 years, and a conditional survival rate of 2 years (if still alive at 6 months from treatment initiation). A total of 673 patients were identified for Period 1—2000 to 2009, 752 for Period 2—2010 to 2017, and 768 for Period 3—2018 to 2020. Median OS in the whole cohort was 11.1, 15.5, and 16.2 months, respectively. Median OS for patients with NSCLC or SCLC was 11.2, 17.2, and 18.2 months, or 10.9, 11.7, and 11.2 months, respectively. The two-year conditional survival was more favorable for NSCLC than SCLC patients. Outcomes were statistically higher for women as compared to men in all periods and all subgroups. Survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC, along with the implementation of novel treatment strategies.