Best of ASCO Philadelphia: Ovarian Cancer Updates from ASCO 2026
Presenter: Mark S. Shahin, MD, FACOG, FACS, Penn State Hershey Medical Center/Penn State Cancer Institute
Conference: Best of ASCO Philadelphia
The Bottom Line
At the 2026 Best of ASCO Philadelphia conference presented by Total Health, Dr Mark Shahin characterized ASCO 2026 as a meeting without an “earth-shattering” gynecologic oncology result, although his review highlighted several developments that could meaningfully expand treatment options for ovarian cancer. Among the most clinically mature findings, he cited the phase III ROSELLA trial which demonstrated significant progression-free survival (PFS) and overall survival (OS) improvements with relacorilant plus nab-paclitaxel in platinum-resistant ovarian cancer (PROC), including those patients with recent prior taxane exposure. The CHRONO trial addressed a different but highly practical question, showing no survival advantage to delaying cytoreductive surgery from three to six cycles of neoadjuvant chemotherapy (NACT), while providing some reassurance when surgery must be delayed in selected patients. At the same time, he noted the ovarian cancer antibody-drug conjugate (ADC) landscape which continues to expand beyond mirvetuximab soravtansine. Early data with the NaPi2b-directed ADC TUB-040 and B7-H4–directed puxitatug samrotecan (Puxi-Sam) suggest additional targets may ultimately become clinically relevant. Dr Shahin also discussed a small, randomized study of short-term fasting during NACT, emphasizing its intriguing biological signal while acknowledging that substantially more evidence is needed before such an intervention can be considered established practice.
ROSELLA Expands Options in Platinum-Resistant Disease
Dr Shahin began by placing newer ovarian cancer strategies in context. Despite considerable enthusiasm for immunotherapy, he cited multiple large, randomized studies which have failed to establish a broad role for immune checkpoint inhibition as part of frontline ovarian cancer treatment. Meanwhile, treatment of recurrent disease has become increasingly biomarker driven, as exemplified by mirvetuximab soravtansine in folate receptor alpha (FRα)-high PROC. ROSELLA, he noted, introduces a different strategy that does not depend on biomarker selection. Relacorilant is a selective glucocorticoid receptor antagonist designed to inhibit cortisol-mediated survival signaling that can reduce tumor sensitivity to chemotherapy. In the phase III study, 381 patients with PROC and one to three previous treatment lines were randomly assigned to relacorilant plus nab-paclitaxel or nab-paclitaxel alone. Nab-paclitaxel was a particularly rational partner because it does not require corticosteroid premedication.
ROSELLA met both primary endpoints; median PFS by blinded independent central review was 6.5 months with relacorilant plus nab-paclitaxel versus 5.5 months with nab-paclitaxel alone (hazard ratio [HR] = 0.70; P=.0076). More importantly, the final analysis demonstrated a substantial OS benefit; median OS was 16.0 versus 11.9 months, corresponding to a 35% reduction in the risk of death (HR = 0.65; P=.0004). Dr Shahin noted that the ASCO analysis focused particularly on whether previous taxane exposure compromised that benefit. Among patients with a taxane-free interval of ≤6 months, median OS was 16.7 versus 11.0 months (HR = 0.60), while among those with a taxane-free interval >6 months, median OS was 15.7 versus 12.1 months (HR = 0.66). Although the short-interval subgroup was small, the overall analysis suggested that prior taxane exposure did not eliminate the benefit of the combination. He also viewed tolerability as, overall, clinically manageable in the trial. Gastrointestinal effects such as nausea, diarrhea, constipation, abdominal pain, vomiting, and decreased appetite were familiar toxicities, while peripheral neuropathy occurred at similar frequencies in the two treatment groups. Dr Shahin emphasized that the regimen provides another treatment option for PROC without requiring biomarker selection.
CHRONO Addresses the Timing of Cytoreductive Surgery
For patients with advanced ovarian cancer who are not candidates for complete upfront cytoreduction, Dr Shahin noted that NACT followed by interval cytoreductive surgery is a well-established strategy. In practice, however, he acknowledges that not every patient is ready for surgery after the conventional three or four cycles. The randomized phase II CHRONO trial addressed whether surgery could instead be delayed until after six cycles of NACT. The study enrolled 209 patients with FIGO stage III to IVA high-grade epithelial ovarian cancer who were initially unsuitable for complete upfront surgery but were considered eligible for complete cytoreduction after three cycles of platinum-based NACT. Patients were randomized either to surgery after three cycles or to receive three additional cycles before delayed surgery.
Results from the trial showed that delayed surgery did not demonstrate superiority for disease-free survival, OS, time to subsequent treatment, postoperative mortality, severe morbidity, or quality of life. There was also no statistically significant difference in major postoperative outcomes between the treatment strategies. For Dr Shahin, however, the value of CHRONO was not that six cycles should replace three as the standard approach. Rather, he believes the study provides evidence to inform situations encountered routinely in clinic when a patient responding to chemotherapy is not yet an optimal surgical candidate: “I’m not saying that this should be the new standard of care, but I think it just gives us a little bit of comfort.” He added that the results give him “at least one piece of data” supporting the possibility of waiting until after cycle six when circumstances require it. Patient selection remains critical, however, and additional studies are needed to determine whether tumor biology or chemosensitivity can identify patients who may specifically benefit from delayed surgery.
ADCs Continue to Reshape the Ovarian Cancer Landscape
In the latter portion of his presentation, Dr Shahin devoted considerable attention to ADCs, beginning with an attempt to move the established FRα-directed ADC mirvetuximab soravtansine into platinum-eligible recurrent disease. The randomized phase II MIROVA/AGO-OVAR 2.34 study enrolled patients with FRα-high recurrent ovarian, fallopian tube, or primary peritoneal cancer who were candidates for platinum therapy. Patients received standard platinum-based chemotherapy or carboplatin plus mirvetuximab soravtansine, followed by maintenance according to the assigned strategy. The combination produced substantially higher response rates than standard platinum therapy, an observation Dr Shahin described as particularly interesting. This higher response rate, however, did not translate into longer PFS, the study's primary endpoint. Ocular toxicity and neuropathy remained important considerations, and the investigators specifically questioned whether the 6-mg/kg adjusted ideal body weight dose was optimal for maintenance treatment. Overall quality of life was maintained. Accordingly, Dr Shahin believes MIROVA does not establish a new standard in platinum-eligible recurrence, but it provides evidence that carboplatin plus mirvetuximab is active and feasible in FRα-high disease while further studies refine where the combination might fit.
TUB-040 and Puxi-Sam: New ADC Targets Emerge
Among earlier-stage agents, Dr Shahin expressed particular enthusiasm for TUB-040, an ADC targeting NaPi2b, a sodium-dependent phosphate transporter highly expressed in high-grade serous ovarian cancer. TUB-040 carries an exatecan payload and was evaluated in the phase I/IIa NAPISTAR 1-01 study in PROC without biomarker selection. This was a heavily pretreated population, with a median of four prior treatment lines; 84% had received bevacizumab, 76% a PARP inhibitor, and approximately 15% mirvetuximab. In the 1.67- to 3.3-mg/kg cohorts, the confirmed objective response rate was 61%, with an unconfirmed plus confirmed response rate of 67%. Median PFS in the overall population was 11.0 months, and 79% of responses lasted longer than six months. Toxicities included nausea, fatigue, and neutropenia, but the overall adverse-event profile was considered manageable. Although Dr Shahin cautioned that these were nonrandomized early-phase data he was nevertheless optimistic: “I predict [this agent] is going to make it to the finish line.” He also raised what may eventually become a major challenge for clinicians: how to sequence multiple ADCs as additional targets and payloads become available.
Dr Shahin briefly highlighted Puxi-Sam (AZD8205) as another emerging ADC. Puxi-Sam targets B7-H4, which is widely expressed in ovarian and endometrial cancers, and uses a topoisomerase I inhibitor payload. He noted that early ovarian cancer activity was accompanied by expected toxicities including neutropenia, nausea, fatigue, and alopecia. While he characterized the antitumor signals as promising, at present this remains an investigational strategy requiring further prospective evaluation.
Could Short-Term Fasting Influence Chemotherapy Response?
One of the more provocative studies in Dr Shahin's review examined short-term fasting during NACT. The biological hypothesis behind the trial was that lowering insulin and other growth-promoting metabolic signals might enhance chemotherapy activity. In this small, randomized study, patients followed either a short-term fasting regimen or a free diet during NACT. Fasting began 36 hours before chemotherapy and continued until 24 hours after treatment, with substantial caloric restriction. The study met its primary metabolic endpoint, in that short-term fasting prevented the chemotherapy-associated increase in insulin levels. Importantly, no significant differences in hematologic or nonhematologic chemotherapy toxicity were observed. Exploratory oncologic findings were intriguing. Median PFS was reported as 38 months with short-term fasting versus 24 months with a free diet (HR = 0.257; 95% CI, 0.062–1.00), and translational analyses suggested possible reductions in immunosuppressive granulocyte and monocyte populations. Dr Shahin notes that these findings should be interpreted cautiously. The study was small and designed primarily around a metabolic endpoint rather than definitive survival comparisons. He also stopped short of recommending routine fasting when asked about his own practice, saying, “I would not say that I have employed it...” although he did, however, describe the findings as thought-provoking and connected them to his broader interest in reducing unnecessary corticosteroid exposure for patients.
Conclusions and Faculty Insights
Rather than a single transformative ASCO 2026 result, Dr Shahin's ovarian cancer review illustrated how the treatment landscape is broadening along several fronts. ROSELLA provided the most mature therapeutic evidence discussed, demonstrating both PFS and OS improvement with relacorilant plus nab-paclitaxel in PROC and showing that benefit persisted across prior taxane-exposure subgroups. CHRONO addressed a different but highly practical clinical issue: three cycles of NACT followed by surgery remains the established approach for appropriate patients, but delaying surgery to six cycles did not appear to compromise major outcomes in the studied population and may provide a reasonable option when circumstances require additional chemotherapy before surgery.
Meanwhile, Dr Shahin cited the ADC landscape which is evolving rapidly. MIROVA demonstrated that moving mirvetuximab into platinum-eligible FRα-high disease can increase response without yet improving PFS, while early TUB-040 and Puxi-Sam results suggest NaPi2b and B7-H4 may become additional actionable ADC targets. These investigational agents also foreshadow an increasingly important question for clinicians: not simply whether to use an ADC, but how to select and sequence ADCs with different targets and payloads. Finally, the short-term fasting study represents an intriguing example of a low-cost supportive care intervention with biological and preliminary clinical signals, but its small size makes confirmation essential before practice changes are warranted. Taken together, Dr Shahin's presentation underscored a field increasingly focused on expanding therapeutic choice while using biomarkers, toxicity profiles, surgical considerations, and patient quality of life to determine how those choices should be applied to individual patients.
Speaker Disclosure Information: Dr Shahin reported no relevant disclosures for this presentation.