BRAIN CANCER

HER2 Breast Cancer

BREAST CANCER

Bladder Cancer

Prostate Cancer

Renal Cell Carcinoma

GENITOURINARY CANCERS

Liquid Biopsies

GENOMIC TESTING

Colorectal Cancer

GIST

Gastric Cancer

GI CANCERS

Cervical Cancer

Endometrial Cancer

Ovarian Cancer

GYNECOLOGIC CANCERS

HEAD & NECK CANCERS

Bone Marrow & Stem Cell Transplant

HEMATOLOGY

CAR T-Cell Therapy

IMMUNOTHERAPY

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

LEUKEMIAS

Biomarker-Driven Lung Cancer

EGFR+ Lung Cancer

MET-Targeted Therapy

Small Cell Lung Cancer

LUNG CANCER

DLBCL

Follicular Lymphoma

Mantle Cell Lymphoma

LYMPHOMAS

MPNs

MULTIPLE MYELOMA

NTRK GENE FUSIONS

SARCOMA

Melanoma

SKIN CANCERS

THYROID CANCERS

NEWS

All News

FDA Briefs

Oncology Icons

Special Reports

The Targeted Pulse

Voices from the Field

CONFERENCES

Conference Coverage

Conference Listing

Data Dialogue with the Oncology Brothers

MEDIA

All Videos

Case-Based Peer Perspectives

Expert Perspective Virtual Tumor Board

Interviews

Investigator Perspectives

Medical World News

Pivotal Practice Views with the Oncology Brothers

Podcasts

Precision Medicine

Speaking Out

PUBLICATIONS

All Publications

Evolving Paradigms

Peers & Perspectives in Oncology

Targeted Therapies in Oncology

CASE-BASED ROUNDTABLE

PARTNERS

RESOURCES

CME/CE

Clinical Trials

Precision Medicine Perspectives

Press Releases

Treatment Resources

SUBSCRIBE

Targeted Oncology provides news, videos, and reviews on the rapidly evolving world of targeted therapies and immunotherapy for oncologists treating patients in a community setting.

About Us

Advertise

Contact Us

CureToday.com

CancerNetwork.com

OncLive.com

OncNursingNews.com

Do Not Sell My Information

Privacy

Terms & Conditions

Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways

Facebook

Linkedin

YouTube

Instagram

Featured Clinical Focus

BTK Inhibitors: In-Focus

Bone Marrow & SCT

EGFR-Positive Lung Cancer

Lung Cancer

Multiple Myeloma

Thyroid Cancers

Clinical Focus

Brain Cancer

Breast Cancer

Gastrointestinal Cancer

Genitourinary Cancers

Gynecologic Cancers

Head & Neck Cancers

Hematology

Leukemias

Lymphomas

Sarcoma

Skin Cancers

Spotlight

1rem

Authors

Amaia Lujambio Goizueta, PhD, discusses the unanswered questions currently circulating the hepatocellular carcinoma field.

Studies in the Hepatocellular Carcinoma Space Leave Unanswered Questions

Amaia Lujambio Goizueta, PhD, discusses a new approach to overcoming resistance to immunotherapy for patients with hepatocellular carcinoma.

Investigating the Role of the Notch Pathway in HCC Immune Resistance

Amaia Lujambio Goizueta, PhD, discusses the challenges and strategies for patients with hepatocellular carcinoma (HCC).

More Research Needed for Patients With Liver Tumors

ASH 2024 Preview for Community Oncologists: The Show and After Show

The American Society of Hematology (ASH) Annual Meeting and Exposition aims to educate oncology providers across an array of hematologic malignancies, with a focus on novel agents, drugs across the FDA pipeline, and more.

, co-hosts Kristie L. Kahl and Andrew Svonavec offer a glimpse at some of the presentations guaranteed to spark one’s curiosity, spur debate, and enhance the field even further. Some key highlights include:

 Continued advancements in CAR T-cell therapy are expected to revolutionize the treatment of hematologic malignancies.

 Bispecific antibodies, such as Epcoritamab (Epkinly), offer a novel approach to target multiple antigens on cancer cells.

 The assessment of MRD is becoming increasingly important in predicting treatment response and overall survival.

Advances in Acute Lymphoblastic Leukemia (ALL)

Blinatumomab (Blincyto) in pediatric ALL:

 The addition of blinatumomab to chemotherapy has shown promise in improving disease-free survival in high-risk pediatric ALL. This combination therapy may offer a more effective treatment option for young patients.

Acalabrutinib (Calquence) in mantle cell lymphoma (MCL):

 The FDA is set to review the approval of acalabrutinib with bendamustine or rituximab (Rituxan) for previously untreated MCL, based on data from the phase 3 ECHO trial (NCT02972840).

Asciminib (Scemblix) in chronic phase chronic myelogenous leukemia (CML-CP):

 The FDA recently granted accelerated approval to asciminib for newly diagnosed CML-CP. This tyrosine kinase inhibitor has shown favorable safety and tolerability profiles.

 isn't just about data, as the duo also offers food recommendations, tourist attractions and fun activities to partake in, as well as interesting facts about San Diego.

This is just a taste of the wealth of information and inspiration waiting at the 2024 ASH Annual Meeting. Check back for future meeting previews with 

Targeted Oncology co-hosts Kristie L. Kahl and Andrew Svonavec highlight abstracts for community oncologists to look out for at the upcoming ASH Annual Meeting in San Diego, with some additional tidbits to round out the main event.

News

The biologics license application (BLA) of the subcutaneous formulation of nivolumab (Opdivo) coformulated with human hyaluronidase (rHuPH20) has been accepted by the FDA.

Findings from the CheckMate -67T (NCT04810078) support this BLA of subcutaneous nivolumab as the trial met its coprimary pharmacokinetic end points and key secondary end point of overall response rate (ORR) vs intravenous (IV) nivolumab in clear cell renal cell carcinoma.

The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date for December 29, 2024.

The FDA has accepted the BLA of the subcutaneous formulation of nivolumab coformulated with rHuPH20, also known as subcutaneous nivolumab, for all previously approved adult solid tumor indications of nivolumab as a monotherapy, monotherapy maintenance following completion of the combination therapy with nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).

Results from the phase 3 CheckMate -67T trial of subcutaneous nivolumab support this application. In the trial, experts sought to evaluate subcutaneous nivolumab vs its intravenous (IV) formulation.

 Here, the subcutaneous form demonstrated noninferior pharmacokinetics and efficacy, as well as consistent safety compared with the IV formulation of nivolumab among patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received prior systemic therapy.

A PDUFA goal date has been set for December 29, 2024. With this, subcutaneous nivolumab shows promise to become the first and only subcutaneously administered PD-1 inhibitor.

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in a press release.

“[Nivolumab] is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV [nivolumab] but with the improved convenience of an injection administered in 3 to 5 minutes rather than a 30- to 60-minute infusion,” Fusaro continued.

The phase 3, randomized, open-label CheckMate -67T trial is exploring subcutaneous administration of nivolumab coformulated with rHuPH20 vs IV nivolumab for the treatment of patients with advanced or metastatic ccRCC who were previously treated with systemic therapy.

In the study, 495 patients were randomly assigned to receive either subcutaneous nivolumab or IV nivolumab. Enrollment was open to patients with a histological confirmation of ccRCC, advanced RCC not amenable to curative or radiation therapy, metastatic RCC, those who received no more than 2 prior systemic therapies, those with intolerance or progression after last treatment regimen within 6 months of randomization, and those with a Karnofsky performance score ≥ 70 at screening.

Experts assessed the coprimary end points of time-averaged serum concentration over 28 days and trough serum concentration at steady-state of subcutaneous nivolumab vs IV nivolumab. A key secondary end point of the trial was ORR.

The study met its coprimary pharmacokinetic end points and key secondary end point of ORR with subcutaneous nivolumab in this patient population.

 Subcutaneous nivolumab was noninferior in regard to time-averaged nivolumab serum concentration over 28 days and steady-state trough serum concentration vs treatment with IV nivolumab. Additionally, subcutaneous nivolumab also demonstrated a noninferior ORR compared with IV nivolumab.

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 6, 2024. 

2. Phase 3 Check-Mate -67T trial of subcutaneous nivolumab (nivolumab and hyaluranisade) meets co-primary end points in advanced or metastatic clear cell renal cell carcinoma. News release. Bristol Myers Squibb. October 19, 2024. Accessed May 6, 2024. 

3. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Updated October 12, 2023. Accessed May 6, 2024. 

https://www.clinicaltrials.gov/study/NCT04810078

The FDA is considering a subcutaneous nivolumab formulation for various solid tumors based on promising data from the phase 3 CheckMate -67T trial. A target action date has been set for December 29, 2024.

Clinical

FDA Accepts BLA for Subcutaneous Nivolumab Across Various Solid Tumors

A statistically significant improvement in overall survival (OS) was observed in patients with unresectable, locally advanced pancreatic adenocarcinoma (PDAC) given tumor treating fields (TTFields) concomitant with gemcitabine and nab-paclitaxel vs the doublet alone in the first-line setting, meeting the primary end point of the PANOVA-3 trial (NCT03377491).

Overall, PANOVA-3 randomized 571 patients to gemcitabine and nab-paclitaxel either alone or combined with TTFields. In the intent-to-treat population, the TTFields regimen led to a median OS of 16.20 months vs 14.16 months for those treated with gemcitabine and nab-paclitaxel alone, making for a statistically significant 2.0-month improvement (HR, 0.819; 

 =.039). Among those treated with TTFields therapy, the survival benefit rate increased over time with a 13% and 33% improvement in the OS rate at 12 and 24 months, respectively.

For safety, treatment with TTFields was well tolerated, and findings were consistent with what has previously been seen in clinical trials.

“As a researcher and clinician, I have experienced the challenges of developing treatments in pancreatic cancer. It is exciting to see the PANOVA-3 trial achieve the positive primary end point of overall survival, a landmark outcome for this field,” said Vincent Picozzi, MD, medical oncologist and investigator in the PANOVA-3 trial, in a press release. “These data for tumor treating fields are very promising, especially in this difficult to treat patient population.”

Full data from the PANOVA-3 study are expected to be presented at an upcoming medical meeting.

Novocure, the company developing TTFields along with Zai Lab Limited, plans to file for regulatory approval of TTFields in the US, European Union, Japan, and other key markets for the treatment of unresectable, locally advanced PDAC. Further, patients continue to be followed in the phase 2 PANOVA-4 trial (NCT06390059), which is evaluating the combination of TTFields therapy with atezolizumab (Tecentriq), gemcitabine, and nab-paclitaxel for the potential treatment of patients with metastatic pancreatic cancer. This study has completed enrollment and is expected to present data in 2026.

“PANOVA-3 is the first and only phase 3 trial to demonstrate a statistically significant benefit in overall survival specifically in unresectable, locally advanced pancreatic cancer, and is Novocure’s third positive phase 3 clinical trial in the last 2 years,” said Nicolas Leupin, MD, PhD, chief medical officer of Novocure, in the press release. “We are grateful to the patients and investigators for their participation in the trial, and we look forward to sharing the full data at an upcoming medical conference.”

PANOVA-3, a prospective, randomized, open-label, controlled, phase 3 trial, was designed to examine the safety and efficacy of TTFields therapy given concomitantly with gemcitabine and nab-paclitaxel in the first-line for the treatment of patients with locally advanced PDAC. A total of 571 patients were enrolled in the study and randomized in a 1:1 fashion.

Patients were randomly assigned to receive either TTFields therapy concomitant with gemcitabine and nab-paclitaxel or gemcitabine and nab-paclitaxel alone. They were then followed for a minimum of 18 months. Gemcitabine was given at a dose of 1000 mg/m

 over 30 minute infusions and was administered immediately post nab-paclitaxel on days 1, 8, and 15 of each 28-day cycle. Nab-paclitaxel was given at 125 mg/m

 via intravenous infusion over 30 to 40 minutes on days 1, 8, and 15 of each 28-day cycle.

Enrollment was open to patients 18 years of age and older with a histological or cytological diagnosis of de novo adenocarcinoma of the pancreas and unresectable, locally advanced stage disease. Patients had to have a life expectancy of at least 3 months and an ECOG performance score of 0, 1, or 2.

In addition to the primary end point of OS, secondary end points consist of progression-free survival (PFS), local PFS, objective response rate, 1-year survival rate, quality of life, pain-free survival, puncture-free survival, resectability rate, and toxicity.

Novocure announces positive topline results from phase 3 PANOVA-3 clinical trial of tumor treating fields (TTFields) therapy for pancreatic cancer. News release. Novocure. December 2, 2024. Accessed December 2, 2024. 

Effect of tumor treating fields (TTFields, 150 kHz) as front-line treatment of locally-advanced pancreatic adenocarcinoma concomitant with gemcitabine and nab-paclitaxel (PANOVA-3). ClinicalTrials.gov. Updated October 31, 2024. Accessed December 2, 2024. 

https://clinicaltrials.gov/study/NCT03377491

The PANOVA-3 trial demonstrated a significant 2-month overall survival improvement when adding tumor treating fields to gemcitabine and nab-paclitaxel for patients with locally advanced pancreatic adenocarcinoma.

Tumor Treating Fields Show Significant Survival Benefit in Pancreatic Cancer

A 52-year-old, postmenopausal woman had a history of grade 2, node-negative invasive ductal carcinoma (IDC).

Estrogen receptor positive (ER+) and progesterone receptor positive (PR+); HER2 immunohistochemistry (IHC) 0; Ki-67 20%​ of the right breast; 21-gene recurrence score, 27

Initial therapy included chemotherapy, radiation therapy, and 5 years of adjuvant anastrozole.

Three years after completing anastrozole​, metastatic progression was discovered, including symptomatic bone involvement (multiple vertebrae and bilateral iliac crests).

Bone marrow aspiration confirmed ER+/PR+, HER2 IHC 0, stage IV IDC.

The patient started letrozole and ribociclib (Kisqali) with denosumab (Xgeva), with good clinical response and marked improvement in her pain​.

Required 1 dose reduction to 400 mg ribociclib due to neutropenia.

Twenty months after starting therapy, routine staging scans showed new FDG-avid sclerotic and lytic bone lesions​.

She noted mild increase in lower back pain​.

Circulating tumor DNA (ctDNA) analysis confirmed an 

Fulvestrant + a different CDK 4/6 inhibitor 

 Using fulvestrant plus a different CDK4/6 inhibitor would not be an unreasonable choice if the patient didn't have an 

 mutation. Fulvestrant alone isn’t a [definite] option for a patient like this. I probably wouldn't use exemestane plus everolimus [Afinitor] here because I don't think this patient has definitively endocrine-resistant disease. Likewise, I probably wouldn't give single-agent chemotherapy. So I would agree with the participants and give elacestrant [Orserdu].

 I absolutely agree. I think elacestrant would be a preferred option.

 But there are some other circumstances where somebody doesn't have access to elacestrant. The 

 mutation would drive me towards a selective estrogen receptor degrader over an aromatase inhibitor combination. So thinking about fulvestrant is also a reasonable option, but I think elacestrant [is a recommended] option.

 The patient received ribociclib in the first-line setting—if she got palbociclib [Ibrance], would you consider, if she didn't have any sort of mutation, fulvestrant plus ribociclib based on the MAINTAIN trial [NCT02632045]?

 I think [we take into account] the MAINTAIN data.

 They are certainly compelling. I have done that very thing in patients who lack other targetable mutations, had a good run on first-line palbociclib, and just have a small amount of progression. We did see data that ribociclib plus fulvestrant was better than fulvestrant alone in that population. I would consider that, remembering that phase 2 hypothesis-generating study.

 mutation, what comes first? How do you deal with that?

 It's a very good question. It's a data-free zone, but I think given the toxicity profile, I probably would lean towards elacestrant.

 I think this depends on the patient in front of you and the volume of their disease. Are they symptomatic, and are we feeling comfortable with single-agent endocrine therapy knowing that we still have the ability to target the PIK3CA pathway at the subsequent progression? I think in the absence of data, it's an art-of-medicine decision. I think there's a place for single-agent endocrine therapy, given the constellation of risk-benefit balance.

During a Case-Based Roundtable® event, Ruth M. O'Regan, MD, looks at options for a patients with hormone receptor–positive, HER2-negative breast cancer and an ESR1 mutation in the second article of a 2-part series.

Amaia Lujambio Goizueta, PhD

Articles

Latest Updated Articles