The evolution of precision oncology: The ongoing impact of the Drug Rediscovery Protocol (DRUP).

BACKGROUND AND PURPOSE: The Drug Rediscovery Protocol (DRUP) is a Dutch, pan-cancer, nonrandomized clinical trial that aims to investigate the efficacy and safety of targeted and immunotherapies outside their registered indication in patients with advanced or metastatic cancer. PATIENTS: Patients with advanced or metastatic cancer are eligible when there are no standard of care treatment options left and the tumor possesses a molecular genomic variant for which commercially available anticancer treatment is accessible off-label in DRUP. Clinical benefit is the study's primary endpoint, characterized by a confirmed objective response or stable disease after at least 16 weeks of treatment. RESULTS: More than 2,500 patients have undergone evaluation, of which over 1,500 have started treatment in DRUP. The overall clinical benefit rate (CBR) remains 33%. The nivolumab cohort for patients with microsatellite instable metastatic tumors proved highly successful with a CBR of 63%, while palbociclib or ribociclib in patients with tumors harboring CDK4/6 pathway alterations showed limited efficacy, with a CBR of 15%. The formation of two European initiatives (PCM4EU and PRIME-ROSE) strives to accelerate implementation and enhance data collection to broaden equitable access to anticancer treatments and gather more evidence. CONCLUSION: DRUP persists in improving patients access to off-label targeted or immunotherapy in the Netherlands and beyond. The expansion of DRUP-like clinical trials across Europe provides countless opportunities for broadening the horizon of precision oncology.

Trastuzumab plus pertuzumab for HER2-amplified advanced colorectal cancer: Results from the drug rediscovery protocol (DRUP).

BACKGROUND: In 2-5% of patients with colorectal cancer (CRC), human epidermal growth factor 2 (HER2) is amplified or overexpressed. Despite prior evidence that anti-HER2 therapy confers clinical benefit (CB) in one-third of these patients, it is not approved for this indication in Europe. In the Drug Rediscovery Protocol (DRUP), patients are treated with off-label drugs based on their molecular profile. Here, we present the results of the cohort 'trastuzumab/pertuzumab for treatment-refractory patients with RAS/BRAF-wild-type HER2amplified metastatic CRC (HER2+mCRC)'. METHODS: Patients with progressive treatment-refractory RAS/BRAF-wild-type HER2+mCRC with measurable disease were included for trastuzumab plus pertuzumab treatment. Primary endpoints of DRUP are CB (defined as confirmed objective response (OR) or stable disease (SD) ≥ 16 weeks) and safety. Patients were enrolled using a Simon-like 2-stage model, with 8 patients in stage 1 and 24 patients in stage 2 if at least 1/8 patients had CB. To identify biomarkers for response, whole genome sequencing (WGS) was performed on pre-treatment biopsies. RESULTS: CB was observed in 11/24 evaluable patients (46%) with HER2+mCRC, seven patients achieved an OR (29%). Median duration of response was 8.4 months. Patients had undergone a median of 3 prior treatment lines. Median progression-free survival and overall survival were 4.3 months (95% CI 1.9-10.3) and 8.2 months (95% CI 7.2-14.7), respectively. No unexpected toxicities were observed. WGS provided potential explanations for resistance in 3/10 patients without CB, for whom WGS was available. CONCLUSIONS: The results of this study confirm a clinically significant benefit of trastuzumab plus pertuzumab treatment in patients with HER2+mCRC.

Exploring Communication About Intimacy and Sexuality: What Are the Preferences of Adolescents and Young Adults with Cancer and Their Health Care Professionals?

Purpose: Negative impact of cancer on sexuality is widely known. In adolescents and young adults with cancer (AYA; 15-39 years), treatment can even have a bigger impact as it may interfere with sexual development. AYAs report unmet psychosexual needs, like inadequate support from health care professionals (HCPs). The aim of this study was to determine preferences of AYAs regarding communication about intimacy and sexuality and examine discrepancies between AYA and HCP. Methods: A cross-sectional survey was conducted among AYAs and HCPs in the Netherlands. Results: Communication about sexuality was considered important by >90% of AYAs and HCPs. Of the AYAs, 41% did receive information from a HCP, 21% of them was satisfied with it. HCPs held physicians and nurse practitioners responsible to discuss sexuality; AYAs preferred nurse practitioners and sexologists. Main barriers to initiate a discussion on sexuality are "feeling of shame" for AYAs and "presence of a third party" for HCPs. Most AYAs would like to receive information about sexuality through a website (66%) or conversation with a HCP (64%) before start of treatment (64%). HCPs would be helped by written material (75%) and additional training (71%) to give to AYAs. Conclusion: AYAs do report unmet needs regarding adequate communication about sexuality-related issues. Discrepancy between patients and HCPs illustrates the importance of patient participation. Future research needs to focus on interventions to improve sexuality-related information provision and implementation of these interventions.