A. Barquín

The efficacy and safety of mirvetuximab soravtansine in FRα-positive, third-line and later, recurrent platinum-sensitive ovarian cancer: the single-arm phase II PICCOLO trial

Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FRα)-targeting antibody-drug conjugate with United States Food and Drug Administration approval for FRα-positive platinum-resistant ovarian cancer. PICCOLO is a phase II, global, open-label, single-arm trial of MIRV as third-line or greater (≥3L) treatment in patients with FRα-positive (≥75% of cells with ≥2+ staining intensity) recurrent platinum-sensitive ovarian cancer (PSOC). Participants received MIRV (6 mg/kg adjusted ideal body weight every 3 weeks) until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death. Primary endpoint was investigator-assessed objective response rate (ORR). Key secondary endpoint was investigator-assessed duration of response (DOR). Additional endpoints included investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Analyses of subgroups by disease characteristics (e.g. platinum-free interval) and treatment history [e.g. prior bevacizumab and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor (PARPi) treatment] were exploratory. Seventy-nine participants were enrolled and efficacy assessable. The primary endpoint was met; ORR was 51.9% [95% confidence interval (CI) 40.4% to 63.3%]. Median DOR was 8.25 months (95% CI 5.55-10.78 months) and median PFS was 6.93 months (95% CI 5.85-9.59 months). OS was not mature at data cut-off. ORR was 45.8% (95% CI 32.7% to 59.2%) in participants with PD while on/within 30 days of prior PARPi (n = 59) and 60.0% (95% CI 14.7% to 94.7%) in those without PD with prior PARPi (n = 5). No new safety signals occurred; most common treatment-emergent adverse events (TEAEs) were gastrointestinal, neurosensory, and resolvable ocular events. TEAEs led to discontinuation in 13 participants (16%) and death in 2 participants (3%). MIRV as ≥3L treatment in heavily pretreated recurrent FRα-positive PSOC demonstrated notable efficacy and tolerable safety, including among those with prior PD on or within 30 days of PARPi (NCT05041257).

Progression-free survival as a surrogate of overall survival in metastatic or recurrent endometrial cancer: an EORTC gynecologic cancer group study.

The value of progression-free survival as a surrogate marker for overall survival remains a matter of debate. Herein, we evaluated the validity of progression-free survival as a surrogate endpoint for overall survival in trials of recurrent or metastatic endometrial cancer. A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Standardized treatment effects (z-scores) for progression-free-survival and overall survival were derived from reported HRs. Pearson's correlation coefficient (r) and surrogate threshold effect (STE) were calculated to assess surrogacy according to German Institute for Quality and Efficiency in Health Care guidelines. Sub-group analyses were performed by treatment modality, line of therapy, and prior radiotherapy exposure. Sixteen randomized trials encompassing 25 treatment comparisons and 10,381 patients with recurrent or metastatic endometrial cancer were included. A strong correlation was observed between z Progression-free survival shows a strong but context-dependent correlation with overall survival among endometrial cancer trials. While it may serve as a valid surrogate marker, particularly in chemoimmunotherapy, its reliability varies by treatment context. These findings support the selective use of progression-free survival as a surrogate in endometrial cancer and underscore the importance of tailored endpoint strategies in oncology trial design.

Mirvetuximab Soravtansine Monotherapy in Platinum-Sensitive Epithelial, Peritoneal, and Fallopian Tube Cancers

PICCOLO (IMGN853-0419) is a Phase 2 multicenter, open label study designed to evaluate the safety and efficacy of Mirvetuximab Soravtansine in participants with platinum-sensitive ovarian, primary peritoneal or fallopian tube cancers with high folate receptor-alpha (FRα) expression.