2026 ASCO Plenary Delivers Practice-Changing Progress

The plenary session at the 2026 ASCO Annual Meeting featured 5 late-breaking abstracts across prostate cancer, sarcoma, lung cancer, and pancreatic cancer, collectively underscoring the accelerating pace of progress across oncology. Here are the key takeaways for everyday oncology practice.

Daraxonrasib Significantly Improves Survival in mPDAC

Daraxonrasib reduced the risk of death by 60% compared with investigator's choice chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC), according to primary and final results from the phase 3 RASolute 302 trial.¹

In the primary analysis population of patients with RAS G12 mutations, median overall survival (OS) was 13.2 months (95% CI, 10.0-not estimable) with daraxonrasib versus 6.6 months (95% CI, 5.4-8.2) with chemotherapy (HR, 0.40; 95% CI, 0.30-0.54; P = 5.9 × 10⁻¹⁰), with 12-month OS rates of 53.3% versus 18.7%. Median progression-free survival (PFS) was 7.3 versus 3.5 months (HR, 0.45; 95% CI, 0.34-0.59; P = 3.2 × 10⁻⁹), and the confirmed objective response rate (ORR) was 33.2% versus 11.8% (P < .0001).

Daraxonrasib also significantly delayed time to deterioration in pain (median 9.2 vs 3.8 months; HR, 0.51; P < .0001) and global health status/quality of life (median 5.7 vs 2.6 months; HR, 0.60; P = .0002). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 43.6% of daraxonrasib patients versus 57.5% with chemotherapy, and TRAEs leading to discontinuation were markedly lower with daraxonrasib (1.2% vs 11.2%).

"The results support daraxonrasib as the new standard of care for patients with previously treated metastatic PDAC," said Brian Wolpin, MD, MPH, Dana-Farber Cancer Institute.

Perioperative Apalutamide Plus ADT Reduces Risk of Metastasis or Death in High-Risk Localized Prostate Cancer

Perioperative apalutamide (Erleada) plus androgen deprivation therapy (ADT) significantly reduced the risk of metastasis or death and made patients with high-risk localized or locally advanced prostate cancer approximately nine times more likely to have little to no cancer remaining in the prostate after surgery compared with placebo plus ADT, according to findings from the phase 3 PROTEUS trial.²

The pathological complete response or minimal residual disease (pCR/MRD) rate was 8.9% with apalutamide plus ADT versus 1.0% with placebo plus ADT (odds ratio, 10.17; P < .0001). At 5 years, 78.2% of patients in the apalutamide arm remained metastasis-free and alive compared with 73.5% in the placebo arm (HR, 0.80; 95% CI, 0.67-0.96; P = .02), representing a 20% reduction in the risk of metastasis or death.

The median event-free survival (EFS) was 57.1 months with apalutamide plus ADT versus 38.4 months with placebo plus ADT (HR, 0.71; 95% CI, 0.63-0.80; P < .0001). Median time to subsequent therapy was 74.2 months versus 41.5 months (HR, 0.65; 95% CI, 0.57-0.73; P < .0001).

The safety profile was consistent with established experience. Skin rash was the most common treatment-emergent adverse event of special interest (33.0% with apalutamide vs 15.3% with placebo). TRAEs leading to death occurred in 7 patients (0.7%) in the apalutamide arm and 1 patient (0.1%) in the placebo arm.

"These results support the perioperative use of apalutamide plus ADT as a new standard of care for patients with localized high-risk prostate cancer," said lead study author Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute.

Adjuvant Selpercatinib Significantly Extends EFS in RET Fusion-Positive NSCLC

Adjuvant selpercatinib (Retevmo) significantly improved EFS compared with placebo in patients with stage II-IIIA RET fusion-positive non–small cell lung cancer (NSCLC), according to results from the phase 3 LIBRETTO-432 trial.³

The median EFS was not reached with selpercatinib versus 31.8 months with placebo (HR, 0.172; 95% CI, 0.058-0.509; P = .0003), representing an 83% reduction in the risk of recurrence or death at a median follow-up of 22.1 months. The 24-month EFS rate was 91.5% versus 61.1%. Only 4 recurrences or deaths occurred in the selpercatinib arm among 54 patients, compared with 17 in the placebo arm.

Grade 3 or higher TRAEs occurred in 66.7% of selpercatinib patients versus 23.7% of placebo patients; the most notable were ALT increase (17.3%), AST increase (18.7%), and hypertension (10.7%). Discontinuation due to adverse events occurred in 17.3% of selpercatinib patients. No treatment-related deaths occurred in either arm.

"The benefits with selpercatinib were consistent across patient subgroups and confirmed by independent review. Adjuvant selpercatinib should be considered as a new standard of care in early-stage RET fusion-positive lung cancer," said lead study author Jonathan Goldman, MD, University of California, Los Angeles.

Abemaciclib Cuts Progression Risk by 62% in Dedifferentiated Liposarcoma

Abemaciclib (Verzenio) reduced the risk of progression or death by 62% compared with placebo in patients with advanced dedifferentiated liposarcoma (DD-LPS), marking the first positive phase 3 clinical trial result ever recorded in this disease, according to findings from the phase 3 SARC041 trial.⁴

Among 108 patients randomized 1:1 to abemaciclib 200 mg orally twice daily or placebo, median PFS was 9.7 months versus 1.5 months (HR, 0.38; 90% CI, 0.25-0.59; P < .001). The 6-month PFS rate was 60% versus 22%, and the 12-month PFS rate was 39% versus 13%. The ORR was 9% with abemaciclib versus 0% with placebo. OS showed a favorable trend despite widespread crossover: median OS was not reached with abemaciclib versus 25.5 months with placebo (HR, 0.55; 95% CI, 0.28-1.07; P = .07), with 24-month OS rates of 72% and 51%, respectively. The most common grade 3/4 toxicities were hematologic (30%), and grade 3 diarrhea occurred in 7%. Dose reduction was required in 39% of abemaciclib patients.

"Dedifferentiated liposarcoma is usually treated with surgery, but when it comes back, it is difficult to treat and often incurable. Chemotherapy has been the standard for decades, but the benefit is modest, delaying progression for 2 to 3 months. This study shows that a pill called abemaciclib that blocks CDK4 may be a new treatment option for patients," said lead study author Mark Dickson, MD, Memorial Sloan Kettering Cancer Center, New York, New York.

Ivonescimab Combo Shows Superior OS in Advanced Squamous NSCLC

Ivonescimab plus chemotherapy significantly improved OS compared with tislelizumab plus chemotherapy in patients with previously untreated advanced squamous NSCLC, according to interim OS results from the phase 3 HARMONi-6 trial.⁵

At a median follow-up of 21.36 months, the median OS was 27.89 months with ivonescimab plus chemotherapy versus 23.69 months with tislelizumab plus chemotherapy (HR, 0.66; 95% CI, 0.50-0.87; P = .0017), crossing the prespecified significance boundary. The 12-month OS rates were 78.9% versus 72.2%, and the 24-month OS rates were 64.7% versus 48.6%. These OS results build on previously reported PFS data showing a significant improvement with ivonescimab plus chemotherapy (median PFS, 11.1 vs 6.9 months; HR, 0.60; 95% CI, 0.46-0.78; P < .0001).

Grade ≥3 TRAEs occurred in 69.2% versus 58.9% of patients. Consistent with ivonescimab's anti-VEGF activity, proteinuria (42.5% vs 12.8%), hemorrhage (24.8% vs 12.1%), and hypertension (14.7% vs 5.7%) were more frequent in the ivonescimab arm, though most events were low grade.

"Squamous NSCLC is associated with worse clinical outcomes than non-squamous NSCLC. This is one of very few studies in advanced squamous NSCLC that has shown median survival beyond 2 years," said lead study author Shun Lu, MD, PhD, Shanghai Chest Hospital, Jiao Tong University School of Medicine, Shanghai, China.

The global phase 3 HARMONi-3 study is currently underway to evaluate ivonescimab in broader populations.

References

1. Wolpin BM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): primary and final analysis from the phase 3 RASolute 302 study. J Clin Oncol. 2026;44(suppl 17):abstr LBA5. Presented at: 2026 ASCO Annual Meeting Plenary Session; May 31, 2026; Chicago, IL.

2. Taplin ME, Gleave M, Shore ND, et al. Perioperative (neoadjuvant and adjuvant) apalutamide + ADT vs placebo + ADT with radical prostatectomy in high-risk localized or locally advanced prostate cancer: final analysis of the PROTEUS phase 3 study. J Clin Oncol. 2026;44(suppl 17):abstr LBA1. Presented at: 2026 ASCO Annual Meeting Plenary Session; May 31, 2026; Chicago, IL.

3. Goldman J, Yang XN, Hochmair M, et al. Event-free survival with adjuvant selpercatinib in stage IB-IIIA RET fusion-positive NSCLC: primary results of the phase 3 LIBRETTO-432 trial. J Clin Oncol. 2026;44(suppl 17):abstr LBA3. Presented at: 2026 ASCO Annual Meeting Plenary Session; May 31, 2026; Chicago, IL.

4. Dickson MA, Ballman KV, Weiss M, et al. SARC041: a phase 3 randomized double-blind study of abemaciclib versus placebo in patients with advanced dedifferentiated liposarcoma. J Clin Oncol. 2026;44(suppl 17):abstr LBA2. Presented at: 2026 ASCO Annual Meeting Plenary Session; May 31, 2026; Chicago, IL.

5. Lu S, Liu B, Luo Y, et al. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China. Lancet. 2026. Presented at: 2026 ASCO Annual Meeting Plenary Session; May 31, 2026; Chicago, IL. Abstract LBA4.