MSK Research Roundup at ASCO 2023: Advances in Glioma, Rectal Cancer, Lung Cancer, Biliary Tract Cancer, and More

MSK researchers presented advances in new treatment approaches for several cancer indications at the 2023 ASCO annual meeting.

Memorial Sloan Kettering Cancer Center (MSK) researchers presented breakthrough advances in new treatment approaches for several cancer indications at the 2023 ASCO Annual Meeting held June 2 to 6, 2023. Highlights of practice-changing study results in glioma, rectal cancer, non-small cell lung cancer, biliary tract cancer, and more were as follows:

Glioma: Targeted Therapy Delays Growth and Need for More Aggressive Treatments for IDH-Mutant Glioma

Vorasidenib significantly delayed the growth of grade 2 isocitrate dehydrogenase (IDH)-mutant glioma and the need for more toxic therapies, according to results from the international phase 3 INDIGO trial (NCT04164901).

Neuro-oncologist Ingo Mellinghoff, MD, FACP, chair of the Department of Neurology, Chief of the Brain Tumor Service and the Evnin Family Chair in Neuro-Oncology at MSK, and lead author of the study, presented the findings in a plenary session. The paper was published simultaneously in The New England Journal of Medicine.

A total of 331 patients with residual or recurrent grade 2 IDH-mutant glioma and no prior treatment other than surgery were randomized to receive vorasidenib (n=168), a brain-penetrant inhibitor of IDH1 and IDH2 metabolic enzymes, or a placebo (n=163). The protocol allowed patients with imaging-confirmed disease progression on placebo to cross over to the vorasidenib group.

Targeted Therapy Delays Growth for IDH-Mutant Glioma

Neuro-oncologist Ingo Mellinghoff, MD, FACP discusses how his research has led to a new targeted therapy for IDH-mutant glioma – and details how this may mark a paradigm shift in therapeutic options for patients with brain tumors.

Watch the interview

At a median follow-up of 14.2 months, 226 patients (68%) remained on treatment. The vorasidenib group showed a statistically significant and clinically meaningful improvement in progression-free survival of 28 months versus 11 months for the placebo group (hazard ratio 0.39). Additionally, time to next intervention was significantly longer in the vorasidenib group versus the placebo group, with a hazard ratio of 0.26. The safety profile of the targeted drug was consistent with earlier studies, with less than 10% of patients developing a serious treatment-related adverse event.

Vorasidenib may represent a paradigm shift in therapeutic options for patients with IDH-mutant glioma, given that currently available therapies are not curative, and patients face significant disease- and treatment-related morbidities and premature death due to disease progression.

Read ASCO 2023 Abstract LBA1. The study was funded by Servier Pharmaceuticals. Access disclosures for Dr. Mellinghoff at

Rectal Cancer: Preoperative FOLFOX Non-Inferior to Preoperative Chemoradiation

In patients with locally advanced rectal cancer eligible for sphincter-sparing surgery, neoadjuvant chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX) was non-inferior to standard of care pelvic chemoradiation with 5-fluorouracil sensitization (5FUCRT), according to results from the multicenter, phase 3 PROSPECT trial (NCT01515787).

Gastrointestinal oncologist Deb Schrag, MD, FASCO, MPH, Chair of the Department of Medicine and the George J. Bosl Chair at MSK and lead author of the study, presented the results in a plenary session. The study was simultaneously published in The New England Journal of Medicine.

Dr. Schrag and colleagues at MSK pioneered the concept for this treatment approach and published findings from their pilot trial in the Journal of Clinical Oncology in 2014. The present PROSPECT trial was a multicenter collaboration led by investigators at the Dana-Farber Cancer Institute.

There were 585 patients in the FOLFOX group and 543 in the chemoradiotherapy group. After five years of follow-up, disease free survival for patients treated with FOLFOX and selective use of 5FUCRT only for those who did not respond to or tolerate FOLFOX was non-inferior to treatment with 5FUCRT. There were also no meaningful differences in overall survival or rates of recurrence between groups.

These results indicate that patients with locally advanced rectal cancer now have two options that offer high cure rates. Patients living in areas where access to radiation settings is challenging or who wish to maintain fertility and sexual function may prefer the all-chemotherapy approach.

Read ASCO Abstract LBA2. The study was funded by the National Cancer Institute Alliance N1048. Access disclosures for Dr. Schrag at

Lung Cancer: Targeted Combination Provides Meaningful Benefit for BRAF V600E-Mutant Non-Small Cell Lung Cancer 

The combination of encorafenib plus binimetinib demonstrated a meaningful clinical benefit in patients with metastatic BRAF V600E-mutant non-small cell lung cancer (NSCLC), according to results from the ongoing international phase 2 PHAROS trial (NCT03915951). The results show that this combination holds promise for becoming a new treatment option for patients.

Thoracic oncologist Gregory Riely, MD, PhD, Vice Chair of Clinical Research in the Department of Medicine at MSK and lead author of the study, presented the findings, which were simultaneously published in the Journal of Clinical Oncology.

Encorafenib is a BRAF kinase inhibitor, and binimetinib is a mitogen-activated protein kinase inhibitor. The combination has demonstrated efficacy and safety in patients with BRAF V600E/K-mutant melanoma. Patients enrolled in the single-arm phase 2 PHAROS study had V600 class 1 BRAF-mutated NSCLC as confirmed by next-generation sequencing or polymerase chain reaction-based testing.

Among 98 patients treated with the combination, 59 were treatment-naive and 39 were previously treated. The objective response rate by independent radiology review was 75% in treatment-naive patients and 46% in previously treated patients, with a median duration of response of not estimable and 16.7 months for each group, respectively. The safety profile was consistent with the approved indication for melanoma.

Read ASCO 2023 Abstract 9018. The study was sponsored by Pfizer. Access disclosures for Dr. Riely at

Biliary Tract Cancer: HER2-Targeted Antibody Zanidatamab Shows Promising Activity

The bispecfic antibody zanidatamab (ZW25) demonstrated rapid and durable responses in pretreated patients with advanced HER2-amplified biliary tract cancer, according to results from the global, single-arm HERIZON-BTC-01 trial (NCT04466891), the largest phase 2 trial to date evaluating HER2-targeted agents in patients with biliary tract cancer.

MSK gastrointestinal oncologist and early drug development specialist James Harding, MD, was lead author of the paper, which was presented at ASCO 2023 and published simultaneously in The Lancet Oncology.

A total of 87 patients were assigned to cohorts based on HER2 immunohistochemistry scores:

Cohort 1 included 80 patients with IHC 2+ or 3+ HER2-positive disease; and cohort 2 included seven patients with ICH 0 or 1+ HER2-positive disease. For cohort 1 patients, the confirmed objective response rate was 41.3%, with a median time to first confirmed response of 1.8 months, a median duration of response of 12.9 months, and a disease control rate of 69%. No responses were observed in cohort 2 patients.

These results support zanidatamab as a potential treatment option for advanced HER2-positive biliary tract cancer. Building on these findings, more studies are underway to evaluate zanidatamab in combination with first-line chemotherapy and as monotherapy for advanced biliary tract cancer.

Read ASCO 2023 Abstract 4008. The study was funded by Zymeworks, Jazz, and BeiGene. Access disclosures for Dr. Harding at

Other Notable MSK Research News from ASCO 2023:

  • Advanced Solid Tumors: First-in-Human Results for a Targeted SHP2 Inhibitor. Initial data from the ongoing, multicenter, first-in-human trial of PF-07284892, an oral, brain-penetrant src homology region 2 domain-containing phosphatase-2 (SHP2) inhibitor, shows it is generally well tolerated as monotherapy and in combination with targeted therapies. After receiving the experimental drug as monotherapy, the novel trial design (NCT04800822) allows patients to receive PF-0784892 in combination with oncogene-matched targeted therapies in the dose escalation phase
  • Advanced Ovarian Cancer: Adding Immunotherapies to Standard of Care Showing Promise in First-Line Setting. The ongoing, multicenter, phase 3 DUO-O study (NCT03737643) is evaluating paclitaxel/carboplatin plus bevacizumab plus durvalumab followed by maintenance therapy with bevacizumab plus durvalumab plus olaparib in treatment-naive patients with newly-diagnosed non-BRCA-mutated advanced ovarian cancer. Following one cycle of chemotherapy, patients are randomized to receive treatment combinations as follows: arm 1, paclitaxel/carboplatin plus bevacizumab followed by maintenance bevacizumab; arm 2, the addition of durvalumab to chemotherapy and bevacizumab followed by maintenance bevacizumab; and arm 3, the addition of durvalumab to chemotherapy plus bevacizumab followed by maintenance olaparib plus durvalumab plus bevacizumab.
    • Interim analysis results showed a statistically significant improvement in PFS for 140 patients in arm 3 versus 143 patients in arm 1, with a hazard ratio of 0.49. PFS was also statistically significantly improved in the intent-to-treat population in the arm 3 versus arm 1, with a hazard ratio of 0.63. The analysis revealed a non-statistically significant improvement in PFS for arm 2 versus arm 1 in the intent-to-treat population at data cut-off.  Safety and tolerability were generally consistent with known profiles for the individual agents. Read ASCO Abstract LBA5506gynecologic oncologist Carol Aghajanian, MD, Chief of MSK’s Gynecologic Medical Oncology Service is co-principal investigator of the trial. Access disclosures for Dr. Aghajanian at
  • Genetic Testing: Ancestry-Adjusted Genomic Analysis Finds Known and Novel Associations with Single and Multiple Cancer Phenotypes. Researchers at MSK conducted a retrospective ancestry-adjusted analysis of genetic testing results for 28,000 patients across 22 cancer types tested over a five-year period with MSK-IMPACT®, which stands for Integrated Mutation Profiling of Actionable Cancer Targets. Their goal was to estimate risk for single and multiple primary cancers.
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