By Richa Madurkar, PharmD, BCOP, Senior Lead Clinical Pharmacist at OncoHealth

Key Takeaways

ASCO 2026, the largest oncology conference in the world, featured groundbreaking clinical trial results expected to transform standards of care (SoC) in oncology. For payors, staying informed about these emerging therapies is essential to ensure timely access to life-extending and life-sustaining treatments for cancer patients.

Here are four trials discussed at the conference that payors should be aware of as they involve off-label therapies already being prescribed or novel agents quickly heading for FDA approval.

perSEVERA BC

Background: This trial was designed to study the combination of giredestrant + palbociclib for frontline management of locally advanced or metastatic ER+/HER2- breast cancer. In this setting, aromatase inhibitor + CDK4/6 inhibitor therapy has been the SoC for over a decade. In this study, patients who have not received any prior treatment for advanced disease were randomized to receive either giredestrant + palbociclib or letrozole + palbociclib. The primary endpoint was investigator-assessed progression-free survival (PFS).

Results: Giredestrant + palbociclib failed to meet its primary endpoint and did not significantly improve PFS, with median PFS 33.1 months in the giredestrant arm vs 28.2 months in the control arm.

Health Plan Impact: While giredestrant will likely not be FDA approved for frontline management of advanced ER+/HER2- breast cancer, this is still an important molecule to watch in the HR+/HER2- setting. It is currently under FDA review as adjuvant monotherapy for early-stage disease and in combination with everolimus after prior CDK4/6 inhibitor therapy for advanced disease based on the results from lidERA BC and evERA BC trials, respectively. FDA decisions are expected for the adjuvant therapy in early-stage and subsequent line in advanced stage indications in November and December 2026, respectively.

LIBRETTO-432

Background: Adjuvant targeted therapy with osimertinib for EGFR mutation+ and alectinib for ALK gene fusion+ for early-stage NSCLC have each shown disease-free survival benefit in the ADAURA and ALINA trials, respectively. However, there is currently no targeted therapy approved for the treatment of early-stage, RET fusion+ NSCLC. This trial studied adjuvant selpercatinib in stage IB, II, or IIIA NSCLC with a RET gene fusion. Selpercatinib was given for up to 3 years after definitive therapy. The primary endpoint was investigator-assessed event-free survival (EFS) in the stage II-IIIA population.

Results: Selpercatinib significantly improved EFS compared to placebo (24-month EFS 91.5% vs 61.1%) in stage II-IIIA disease. The EFS benefit was also seen in the overall population (24-month EFS 96.8% vs 78.4%).

Health Plan Impact: Currently, selpercatinib is only FDA approved for advanced or metastatic RET fusion+ NSCLC. NCCN guidelines now endorse the use of this agent in the adjuvant setting after resection based on results of this fully published trial. This study continues to highlight the emergence of biomarker testing in early-stage NSCLC prior to starting therapy, as there are now several mutations that, if identified, could impact the choice of adjuvant therapy.

PROTEUS

Background: This study evaluated incorporation of apalutamide, an androgen receptor inhibitor, into an earlier phase of the prostate cancer treatment paradigm. Currently, apalutamide is approved for use in the metastatic castrate-sensitive or non-metastatic castrate resistant prostate cancer. In PROTEUS, patients with high-risk prostate cancer planned for radical prostatectomy were randomized to receive 1-year of peri-operative apalutamide in combination with androgen deprivation therapy (ADT) or placebo with ADT. The dual primary endpoints were pathologic complete or minimal residual disease (pCR/MRD) and metastasis-free survival (MFS).

Results: The rate of achieving pCR/MRD at time of surgery was improved with apalutamide compared to placebo (8.9% vs 1%). There was a 20% reduction in the risk of developing metastasis or death in the apalutamide arm.

Health Plan Impact: This study supports the use of apalutamide in high-risk localized prostate cancer. While this indication is not currently supported by the FDA or NCCN guidelines, the trial is fully published. Health plans can expect increases in spend on this agent based on the benefit that was seen in a broad population. It is important to note that other androgen receptor pathway inhibitors (ARPIs) have not been studied in the peri-operative setting; extrapolation of these findings to other ARPIs is not currently supported.

RASolute 302

Background: The current SoC for previously treated metastatic pancreatic adenocarcinoma is cytotoxic chemotherapy, but this option is associated with modest survival outcomes. Daraxonrasib is a novel oral RAS(ON) multi-selective tyrosine kinase inhibitor (TKI). In this study, patients with metastatic pancreatic adenocarcinoma who were previously treated with chemotherapy, were randomized to receive daraxonrasib or investigator’s choice of chemotherapy. The primary endpoints were OS and PFS in the RAS G12C mutated population.

Results: In the RAS G12C mutated population, daraxonrasib significantly improved the median OS (13.2 vs 6.6 months) and median PFS (7.3 vs 3.5 months) compared to chemotherapy. These outcomes were also similar in the overall population regardless of RAS mutation status. The most common adverse events with daraxonrasib were rash, diarrhea, stomatitis, and nausea/vomiting.

Health Plan Impact: Daraxonrasib is currently investigational but is likely to be the new SoC in this pretreated population, regardless of RAS mutation status. Ongoing studies are evaluating daraxonrasib for resected disease after perioperative therapy (RASolute 304) and for frontline treatment of metastatic disease with or without albumin-bound paclitaxel (RASolute 303). This therapy has the potential to transform outcomes in this difficult-to-treat population.

Additional Noteworthy Data

• Ivonescimab is a first-in-class PD-1/VEGF dual-target bispecific antibody. At ASCO 2026, the results from HARMONi-6 were presented. This study found ivonescimab + chemotherapy significantly improved OS compared to tislelizumab + chemotherapy in a Chinese population with previously untreated advanced squamous NSCLC (mOS 27.9 months vs 23.7 months). The global HARMONi-3 phase III study comparing ivonescimab + chemotherapy to pembrolizumab + chemotherapy for front-line management of metastatic squamous or nonsquamous NSCLC is underway to see if this benefit may be seen in other geographical regions. Ivonescimab is currently being reviewed by the FDA for locally advanced or metastatic NSCLC with an EGFR mutation after progression on EGFR-targeting TKI therapy with a PDUFA date of November 14, 2026. If approved for this indication, plans may receive off-label requests for the treatment naïve, advanced, squamous NSCLC population.
• Abemaciclib is a CDK4/6 inhibitor that is already FDA approved in breast cancer but has shown promising results in sarcoma based on the recent SARC041 study. In this study, abemaciclib significantly improved PFS compared to placebo in patients with recurrent or metastatic dedifferentiated liposarcoma (mPFS 9.7 months vs 1.5 months). The median OS was not reached with abemaciclib vs 25.5 months with placebo.

  This is a rare and aggressive tumor with a high unmet need. Current therapeutic options are limited to cytotoxic chemotherapy that confer a mPFS of less than four months. In the NCCN guideline for Soft Tissue Sarcoma, abemaciclib is currently supported for dedifferentiated liposarcoma with or without concurrent well-differentiated liposarcoma as a category 2A recommendation.

These studies were just some of the many presentations at ASCO 2026. The conference showcased novel entities that are rapidly headed for FDA approval, as well as expanded indications for drugs that are already commercially available. It’s crucial for health plans to be aware of these innovations to ensure patients have access to evidence-based therapies that improve outcomes in a cost-effective manner.