2024 ASCO Annual Meeting Highlights: Key Findings for Oncology Pharmacy Practice

Douglas Braun, PharmD, CSP, RPh;

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July 16, 2024

Pharmacy Practice in Focus: Oncology

July 2024

Volume 6

Issue 5

2024 ASCO Annual Meeting Highlights: Key Findings for Oncology Pharmacy Practice

Author(s):

Douglas Braun, PharmD, CSP, RPh

Data presented show significant advancements in treatment options.

The American Society of Clinical Oncology (ASCO) Annual Meeting was held May 31 to June 4, 2024, in Chicago, Illinois, featuring more than 200 sessions educating attendees on the latest information from oncology research. Below are some valuable highlights from these sessions for oncology pharmacy clinical practice.

Lung Cancer

Image credit: Aydan | stock.adobe.com

Phase 3 CROWN Trial

Significant progression-free survival (PFS) advantage was demonstrated with lorlatinib (Lorbrena; Pfizer Inc) vs crizotinib (Xalkori; Pfizer Inc) in patients with previously untreated, advanced ALK-positive non–small cell lung cancer (NSCLC). The results from the phase 3 CROWN trial (NCT03052608) demonstrated a median PFS (mPFS) of not reached (NR) in the lorlatinib group vs 9.1 months in the crizotinib group. Time to brain disease progression was NR again for lorlatinib vs 16.4 months in the crizotinib group.¹

Phase 3 LAURA Trial

In the phase 3 LAURA trial (NCT03521154), osimertinib (Tagrisso; AstraZeneca) was shown to improve PFS in unresectable, stage III, EGFR-mutated NSCLC after chemoradiotherapy. The trial findings revealed an mPFS of 39.1 months in the osimertinib arm vs 5.6 months in the placebo arm. Overall survival (OS) data trended toward favorable, but crossover after disease progression has affected the reportability of the data.²

Phase 3 PALOMA-3 Trial

Findings from the phase 3 PALOMA-3 trial (NCT01942135) showed few clinical differences between subcutaneous (SQ) and intravenous (IV) administration of amivantamab (Rybrevant; Janssen Biotech Inc) in patients with EGFR-mutated NSCLC. The data also proved noninferiority in area under the curve and trough concentration of administering amivantamab SQ vs IV when given in combination with lazertinib (Leclaza; Yuhan and Janssen Biotech Inc). Administration time was reduced from 5 hours to 5 minutes for cycle 1 on day 1 and 2 hours to 5 minutes for subsequent administrations. Administration-related reactions were reduced from 66% to 13% by changing the route of administration.³

Phase 3 ADRIATIC Trial

Findings from the phase 3 ADRIATIC study (NCT03703297) demonstrated that durvalumab (Imfinzi; AstraZeneca) administration as consolidation treatment for limited-stage small cell lung cancer (LS-SCLC) significantly improved survival after concurrent chemoradiation in patients with LS-SCLC. At 37.2 months, the OS was 55.9 months in the durvalumab arm vs 33.4 months in the placebo arm. At 27.6 months, the mPFS was 16.6 months vs 9.2 months, respectively.⁴

Phase 2 TRUST-I Trial

In findings from the phase 2 TRUST-I trial (NCT04395677), next-generation ROS1 tyrosine kinase inhibitor (TKI) taletrectinib (AB-106; AnHeart Therapeutics) demonstrated an objective response rate (ORR) of 90.6% in TKI-naive patients with ROS1-positive NSCLC. The median duration of response (mDOR) and mPFS at 23.5 months was NR. For patients previously treated with crizotinib, the median ORR was 51.5%, the DOR was 10.6 months at 9.7 months, and the mPFS was 7.6 months. For patients with a G2032R mutation, the ORR was 66.7%.⁵

Phase 3 KRYSTAL-12 Trial

The phase 3 KR YSTAL-12 trial (NCT04685135) assessed adagrasib (Krazati; Bristol Myers Squibb) vs docetaxel in previously treated patients with KRAS G12C–positive NSCLC. The trial data showed an mPFS increase of 5.5 months vs 3.8 months in the adagrasib and docetaxel arms, respectively, as well as an ORR of 32% vs 9% and an mDOR of 8.3 months vs 5.4 months, respectively. A 24% intracranial response was seen in patients with central nervous system metastasis at baseline vs 11% in the docetaxel arm.⁶

Phase 2 TROPION-Lung05 Trial

In a post hoc analysis of the phase 2 TROPIONLung05 trial (NCT04484142), investigators observed intracranial antitumor activity with datopotamab deruxtecan (Dato-DXd) in previously treated patients with advanced or metastatic NSCLC, including those with brain metastases at baseline. The analysis showed that in this population, patients with baseline brain metastases had an ORR of 28% and a disease control rate of 72%, with an mPFS similar in patients with and without brain metastasis. Additional analyses of the intracranial activity of Dato-DXd are being conducted in the phase 2 TUXEDO-2 trial (NCT05866432) and the phase 2 DATO-BASE trial (NCT06176261).⁷

Lymphomas

Phase 1 UPCC15420 Trial

In an attempt to boost longer-term remission with chimeric antigen receptor (CAR) T-cell therapy, the phase 1 UPCC15420 trial (NCT04684563) investigators are testing a fourth-generation “armored” anti-CD19 CAR T-cell therapy that is modified to secrete IL-18, which may demonstrate enhanced CAR T-cell activity. Investigators are testing in non-Hodgkin lymphoma, and a 3-month ORR of 80% was reached in patients who were previously treated with commercially available CAR T-cell therapy. The new process also has reduced the manufacturing time from 9 to 14 days down to 3 days. No additional safety concerns were seen with the IL-18 production.⁸

Chronic Myelogenous Leukemia

Phase 3 ASC4FIRST Trial

Results of the phase 3 ASC4FIRST trial (NCT04971226) showed asciminib (Scemblix; Novartis) had a statistically superior major molecular response (MMR) and a more favorable safety and tolerability profile than other TKIs for patients with newly diagnosed chronic myelogenous leukemia (CML). ASC4FIRST was a global trial with more than 400 patients with newly diagnosed CML from 29 countries that compared MMR rates of asciminib with first-line TKI therapies approved in the chronic-stage setting. At 48 weeks, asciminib had an MMR rate of 67.7% vs 49% for a standard TKI treatment, with 86% of patients on asciminib still on treatment vs 62% of patients on imatinib (Gleevec; Novartis) and 75% of patients on a second-generation TKI. Additionally, grade 3 or higher adverse events (AEs) were seen in 38% of patients receiving asciminib, 44% receiving imatinib, and 55% in the second-generation TKI arm.⁹

Colorectal Cancer

Phase 1 PROCEADE-CRC-01 Trial

The novel anti-CEACAM5 antibody-drug conjugate M9140 showed early potential in patients with metastatic colorectal cancer (CRC); CEACAM5 is a cell surface protein found in more than 90% of patients with CRC. The phase 1 PROCEADE-CRC-01 trial (NCT05464030) findings showed an mPFS of 6.7 months and a 42.5% stable disease rate in advanced, heavily pretreated disease. No events of ocular toxicity or interstitial lung disease (ILD) were reported.¹⁰

Phase 2 Dostarlimab Trial

Follow-up data from a phase 2 trial (NCT04165772), which were originally presented in 2023, showed that a 6-month course of dostarlimab (Jemperli; GSK) in patients with mismatch repair–deficient (dMMR) locally advanced rectal cancer achieved a complete response in all patients, with no patients requiring chemotherapy, chemoradiation, or surgery. No grade 3 AEs were seen in the treatment arm.¹¹

Esophageal Cancer

Phase 3 ESOPEC Trial

The phase 3 ESOPEC trial (NCT02509286) findings showed that patients with resectable esophageal cancer who underwent perioperative chemotherapy with docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT protocol) had a significant OS benefit when compared with neoadjuvant chemoradiation (CROSS protocol). At a 55-month median follow-up, patients receiving the FLOT protocol had a median OS (mOS) of 66 months vs 37 months (CROSS protocol) in patients with resectable esophageal cancer.¹²

Multiple Myeloma

Phase 3 DREAMM 8 Trial

The phase 3 DREAMM 8 study (NCT04484623) compared belantamab mafodotin (Blenrep; GSK) plus pomalidomide (Imnovid; Bristol Myers Squibb) and dexamethasone (BPd) with pomalidomide plus bortezomib (Velcade; Takeda Oncology) and dexamethasone (PVd) for patients with relapsed/refractory multiple myeloma (MM). The results of this study showed that the BPd regimen showed significant PFS benefit in this patient population following 1 or more prior lines of therapy. The results also showed that at a median follow-up of 21.8 months, the BPd combination had an mPFS of NR vs 12.7 months in the PVd arm. This may provide the drug with an opportunity to move back to the market, with low rates of discontinuation due to ocular AEs along with reversibility of AEs with dose modifications.¹³

IMROZ Trial

In the IMROZ trial (NCT03319667) findings, the estimated PFS rate at 60 months was 63.2% in patients with newly diagnosed, transplant-ineligible MM who were treated with isatuximab (Sarclisa; Sanofi) with the standard backbone of bortezomib, lenalidomide (Revlimid; Celgene Corporation), and dexamethasone (VRd) compared with 45.2% for those treated with VRd alone (HR, 0.60; 98.5% CI, 0.41-0.88; P < .001). PFS benefit was also observed in most of the study subgroups, with the exception of those with high-risk cytogenetic features (HR, 0.97; 95% CI, 0.48-1.96).¹⁴

BENEFIT Trial

In findings from a second trial demonstrating that isatuximab plus VRd improves outcomes in patients with MM, the BENEFIT trial (NCT04751877) findings showed that at 18 months, isatuximab-VRd significantly improved minimal residual disease negativity (53% vs 26%) when compared with isatuximab-Rd. Although AEs leading to discontinuation were lower in the isatuximab group, grade 3 or higher AEs were also elevated, including 11% grade 5 AEs (vs 5.5% in the VRd group).¹⁴

Breast Cancer

Phase 3 DESTINY-Breast06 Trial

The phase 3 DESTINY-Breast06 trial (NCT04494425) findings demonstrated that fam-trastuzumab deruxtecannxki (T-DXd; Enhertu; AstraZeneca and Daiichi Sankyo) showed statistically significant and clinically meaningful improvement in PFS compared with standard-of-care chemotherapy in patients with hormone receptor–positive, HER2-low (immunohistochemistry 1+ or 2+, in situ hybridization negative) metastatic breast cancer following 1 or more lines of endocrine therapy (ET). For patients with prior ET and CDK4/6 therapy, the mPFS was 13.2 months on T-DXd vs 8.1 months on chemotherapy (capecitabine plus nab-paclitaxel or paclitaxel). The ORR was 56.5% and 61.8% (vs 32.3% and 26.3%) for HER2-low and HER2-ultralow disease, respectively, and the median duration of therapy was 11 months vs 5.6 months, respectively. ILD occurred in 11%, leading to a 5% discontinuation rate, and there were 3 deaths from ILD.¹⁵

Acute Myeloid Leukemia

Abstract 6507

For newly diagnosed patients with acute myeloid leukemia who are either older or ineligible for chemotherapy, reducing the duration of venetoclax (Venclexta; AbbVie) from 28 days to 7 days when in combination with azacitidine (Vidaza; Bristol Myers Squibb) resulted in similar remission rates and mOS with lower incidences of toxicities, including a reduction in the number of required transfusions and a lower early mortality.¹⁶

Melanoma

Phase 1/2 IMC-F106C Trial

Novel agent IMC-F106C showed activity and a good safety profile for cutaneous melanoma. IMC-F106C, a protein-based drug, is being tested in the heavily pretreated, advanced/metastatic cutaneous melanoma space. Findings from the phase 1/2 trial (NCT04262466) assessing IMC-F106C in this population showed a disease control rate of 56%, a tumor reduction rate of 28% and a molecular response rate of 42%. Further testing will determine whether this bispecific fusion protein will find a place in management of this aggressive disease.¹⁷

Phase 2 NADINA Trial

In the phase 2 NADINA trial (NCT04949113) results, investigators observed that giving neoadjuvant ipilimumab (Yervoy; Bristol Myers Squibb) and nivolumab (Opdivo; Bristol Myers Squibb) significantly reduced the risk of disease recurrence or death compared with standard adjuvant therapy in patients with stage III melanoma. Investigators only provided adjuvant therapy if there was not a deep response; however, with neoadjuvant therapy, investigators found fewer disease-related events and a 27% absolute reduction in 12-month disease recurrence risk. Investigators estimated that at 12 months, 83.7% of patients receiving neoadjuvant therapy would be event free vs 57.2% for patients receiving only the adjuvant treatment.¹⁹

Gynecologic Cancer

Phase 2 KN035-CN-011 Trial

SQ envafolimab (Enweida; TRACON Pharmaceuticals) plus lenvatinib (Lenvima; Eisai Co Ltd) demonstrated durable ORR in patients with advanced endometrial cancer who did not have microsatellite instability–high or dMMR disease after prior lines of therapy. The phase 2 KN035-CN-011 trial (NCT05112991) findings showed an ORR of 40% and a disease control rate of 84%. The mPFS was 9.2 months, and the mDOR was 7.5 months.¹⁸

Hepatocellular Cancer

Phase 3 CheckMate 9DW Trial

Findings from the phase 3 CheckMate 9DW trial (NCT04039607) demonstrated that nivolumab plus ipilimumab had an mOS of 23.7 months, which is 3 months longer than with either lenvatinib or sorafenib (Nexavar; Bayer). The ORR was 36% for the nivolumab/ipilimumab arm vs 13% for the patients on either oral agent. The mPFS was similar at 9.1 months but higher at 18 months (34% vs 18%, respectively) and at 24 months (28% vs 12%, respectively). The immunotherapy combination reduced the risk of symptom deterioration by 24% compared with either oral agent.¹⁹

General ASCO News

American Cancer Society and ASCO Partnership

ASCO announced a partnership with the American Cancer Society to create a fully comprehensive database of resources for patients to receive credible information about cancer. With this collaboration, cancer.org and cancer.net will combine to provide high-quality education to patients and caregivers. In mid-June, visitors to cancer.net will be redirected to cancer.org.5

GLP-1 Receptor Agonists Reduce Obesity-Related Cancers

About the Author

Douglas Braun, PharmD, CSP, RPh, is a senior pharmacy director for the American Oncology Network, LLC, in Naples, Florida.

For patients with a body mass index of 35 or greater, glucagon-like peptide-1 receptor agonists were shown to reduce the risk of obesity-related cancers at a rate similar to those undergoing bariatric surgery, suggesting these drugs as a nonsurgical viable option. At 15 years, both interventions had a superior all-cause mortality compared with no intervention.¹²

References