BRAIN CANCER

HER2-Positive Breast Cancer

BREAST CANCER

Bladder Cancer

Prostate Cancer

Renal Cell Carcinoma

GENITOURINARY CANCERS

Liquid Biopsies

GENOMIC TESTING

Colorectal Cancer

GASTRIC CANCER

GIST

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

MET-TARGETED THERAPY

SMALL CELL LUNG CANCER

BIOMARKER-DRIVEN LUNG CANCER

EGFR+ 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

Voices from the Field

CONFERENCES

Conference Coverage

Conference Listing

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

PUBLICATIONS

All Publications

Evolving Paradigms

Roundtable Meetings Spotlight

Targeted Therapies in Oncology

CME/CE

RESOURCES

Case-Based Roundtable Series

Clinical Trials

Partners

Precision Medicine Perspectives

Press Releases

Treatment Resources

SUBSCRIBE

eNewsletter

Print Subscription

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

Twitter

YouTube

Instagram

Featured Clinical Focus

BTK Inhibitors: In-Focus

Biomarker-Driven Lung Cancer

Bone Marrow & SCT

CAR T-Cell Therapy

EGFR-Positive Lung Cancer

Endometrial Cancer

Lung Cancer

Small Cell Lung Cancer

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

Clinical

TAK-21-TTD0548 - /clinical/lung

In season 1, episode 1 of Targeted Talks, community physician Jason R. Williams, MD, DABR, interventional radiologist, Williams Cancer Institute, leads a discussion with George R. Simon, MD, FACP, FCCP, medical oncologist, The University of Texas MD Anderson Cancer Center, about the use of immunotherapy in patients with non–small cell lung cancer (NSCLC), whether treated in an academic or community setting, and how this could be challenged with the discovery of a genetic driver alteration.

During the discussion, the 2 experts cover the pros and cons of immunotherapy use and how they differ in the community setting versus the academic setting, the available tools for profiling patients, promising immune checkpoint inhibitors for the treatment of NSCLC, key genetic drivers in NSCLC, and choosing the optimal subsequent therapy for patients with NSCLC.

Community physician Jason Williams, MD, DABR, talks to academic oncologist George R. Simon, MD, FACO, FCCP, for an episode of Targeted Talks.

Individualizing Immunotherapy in Non–Small Cell Lung Cancer

The phase 3 LUNAR trial evaluating tumor treating fields with standard-of-care therapies met its primary end point in patients with metastatic non–small cell lung cancer.

TTFields With SOC Induces Clinically Meaningful Survival Results in mNSCLC

Phase 2 results have placed a novel EGFR exon 20 insertion inhibitors in the realm of possibilities for future treatment of previously-treated non–small cell lung cancer with EGFR exon 20 insertions in the tumor tissue.

Sunvozertinib Shows Activity, Tolerable Safety in EGFR Exon20 Insertion-Positive NSCLC

New results from the TROPION-Lung02 trial highlight the potential of the antibody-drug conjugate datopotamab deruxtecan with pembrolizumab for patients with advanced non–small cell lung cancer.

Datopotamab Deruxtecan/Pembrolizumab Combo Show Anti-tumor Activity in Advanced NSCLC

Data from CheckMate 9LA trial  further support the use of nivolumab plus ipilimumab and chemotherapy as an efficacious first-line treatment option for patients with metastatic NSCLC, says David P. Carbone, MD, PhD.

Nivolumab/Ipilimumab Plus Chemotherapy as Frontline Therapy Shows Continued Efficacy in mNSCLC

Patients with non–small cell lung cancer who completed definitive surgery saw clinical benefits after being treated with neoadjuvant nivolumab and chemotherapy.

Neoadjuvant Nivolumab and Chemotherapy Shows Continued Benefit in NSCLC Exploratory Analysis

Liza C. Villaruz, MD, associate professor of medicine and co-leader of the Immunotherapy and Drug Development Center at UPMC Hillman Cancer Center, discusses the most promising biomarkers in the non–small cell lung cancer (NSCLC) space.

She says that the known driver mutations in oncogenes have been most successful, such as 

. There are approved targeted therapies for these alterations that are effective enough to be used as frontline therapy for patients with NSCLC, making broad genetic testing important for patients with advanced disease.

PD-L1 is also an important biomarker since PD-L1 expression level is predictive of benefit in patients who receive immune checkpoint inhibitors alone or in combination with other therapies. This includes pembrolizumab (Keytruda) monotherapy and combination nivolumab (Opdivo) plus ipilimumab (Yervoy), which targets both PD-1 and CTLA-4.

In terms of upcoming therapy targets, Villaruz says research will show whether TROP expression is predictive of response to TROP2 inhibitors such as the antibody-drug conjugate (ADC) datopotamab deruxtecan; if so, this will be another valuable biomarker. The adhesion molecule CEACAM5 is another biomarker with a novel therapy tusamitamab ravtansine (SAR408701) under investigation in the phase 2 CARMEN-LC05 trial (NCT04524689). Additionally, 

 may become a more significant biomarker, as research into c-MET ADCs including telisotuzumab vedotin has shown potential for patients with 

 We have our oncogene driven disease, and they are the gold standard in terms of predictive biomarkers of therapeutic benefit with regard to 

. We have PD-L1, which is the gold standard for predicting therapeutic benefits to immunotherapy, either by itself, chemoimmunotherapy combinations, or immunotherapy/immunotherapy combinations—combined PD-1 and CTLA-4 therapies.

I think as we go forward, [it will] be interesting to see how TROP…is predictive of benefit to TROP2 inhibitors, and also CEACAM5, because there are novel therapies aimed toward that as well. I think it'll be interesting to see how all of these different biomarkers could potentially predict the benefit of their targeted agents. There is still a fair amount of work with 

, and several different MET ADCs, which are also within development.

Videos

Liza C. Villaruz, MD, discusses the most promising biomarkers in the non–small cell lung cancer space.

Top Targets and Novel Biomarkers Attract Interest in NSCLC

David S. Hong, MD, deputy chair, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses updated findings from an analysis of 3 trials which ultimately led to the approval of larotrectinib (Vitrakvi) for patients with solid tumors that harbor an 

These studies include the phase 2 NAVIGATE (NCT02576431), phase 1 LOXO-TRK-14001 (NCT02122913), and phase 1/2 SCOUT (NCT02637687) trials which each evaluated larotrectinib as an NTRK inhibitor.

Looking at each trial, SCOUT, NAVIGATE, and LOXO-TRK-14001, Hong notes that larotrectinib continues to show robust and durable objective responses when used to treat patients with 

 fusions. The agent also demonstrated to have a favorable long-term safety profile in the analysis.

In this most recent analysis, we looked at close to 244 patients. In those 244 patients, we looked at response rates, progression-free survival, duration of response, and overall survival. It's always amazing to me when I see this updated data, how durable and how beneficial this drug is in these patients. The overall response rate remained very high, close to 70%, 69%, with complete response rates of over 21%. The median duration of response was 32.9 months, with median progression-free survival at 29.4 months, and the overall survival had yet to be reached across all different pathologies.

 The overall safety signal, including in the phase 1 trial and all the other studies of about 269 patients, the vast majority of adverse events had only been grades 1 and 2. About 20% of the patients had grade 3 treatment related adverse events, mostly related to elevated liver function tests, which were usually reversible once the drugs were held, and dose reduced. This was pretty much the same thing that we saw with larotrectinib with the initial approval at 55 patients.

In this expanded analysis, larotrectinib continued to show robust and durable objective responses in patients with 

 fusions and a favorable long-term safety profile. It speaks to the fact that with next generation sequencing [NGS] being a common test that we can get in our patients, it behooves every oncologist to try to find these patients through NGS testing.

David S. Hong, MD, discusses updated findings from an analysis of 3 trials which ultimately led to the approval of larotrectinib for patients with solid tumors who harbor an NTRK fusion.


News

Evaluating Larotrectinib for TRK Fusion-Positive Lung Cancer Across 3 Trials

Cary Gross, MD, professor of medicine and of epidemiology, and founder and director, the Cancer Outcomes, Public Policy and Effectiveness Research Center, Yale School of Medicine; director, Adult Primary Care Center, Quality Improvement; chair, National Clinician Scholars Program; and director, National Clinician Scholars Program, discusses the findings from a retrospective study which revealed there to be an association between Medicaid insurance, rates of biomarker testing, and patient outcomes among patients with advanced non–small cell lung cancer (NSCLC).

The study was published in the Journal of the National Comprehensive Cancer Network and assessed 6,145 commercially insured patients and 865 Medicaid beneficiaries with advanced NSCLC. Data was collected from electronic medical records of patients with advanced NSCLC who were between the ages of 18 and 64. The recommended biomarker tests for advanced NSCLC include 

 gene alterations, as well as PD-L1 expression, and the recommended biomarker-driven therapies for advanced NSCLC were immunotherapy or tyrosine kinase inhibitor treatment.

Findings revealed that Medicaid beneficiaries were less likely to have gotten biomarker testing (HR, 0.81; 

 < .001), any first-line treatment (HR, 0.72; 

 < .001), or first-line biomarker-driven therapy (HR, 0.70; 

 < .001) compared with commercially insured patients. Those weho were Medicaid beneficiaries also were more likely to be Black or African American (20% and 9.3%) (

 < .001), respectively. This also showed that they were less likely to undergo biomarker testing at 57% vs 71% (

The natural question was, if the Medicaid patients are less likely to get biomarker testing, are they also less likely to get biomarker-driven therapy? And, as one would expect, that's exactly what we found. Medicaid beneficiaries were 30% less likely to receive biomarker-driven therapy, then commercially insured patients. Unfortunately, we also found that patients with Medicaid had a 23% higher risk of death than patients with private insurance. Then, what we did is we then adjusted in our model for whether each individual patient had received biomarker testing and biomarker treatment.

We looked at the difference in mortality without adjusting for who got [testing]. And as I mentioned, the Medicaid patients were 23% more likely to die, then we accounted for who got testing and treatment. And we found that the relative risk decreased somewhat so the higher risk was down to 15% associated with Medicaid. What that means is [with] unadjusted Medicaid, 23% had higher risk of death. After we accounted for biomarker testing and treatment, Medicaid patients [had a] 15% higher risk of death. That means that a fair proportion of this disparity in survival in Medicaid patients can be attributed to this lack of access to testing and treatment. These findings strongly suggest that treatment is 1 of the main culprits in why Medicaid patients with lung cancer are having worse outcomes.

Cary Gross, MD, discusses the findings from a retrospective study which revealed there to be an association between Medicaid insurance, rates of biomarker testing, and patient outcomes among patients with advanced non–small cell lung cancer.


Link Between Medicaid and Rates of Biomarker Testing in NSCLC

Alexander Drilon, MD, medical oncologist and chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, discusses what to know when testing for 

 gene fusions in patients with lung cancer.

According to Drilon, testing to find these types of gene fusions is important, and some of the best ways to do so are with comprehensive next-generation sequencing of the DNA and RNA.

 gene fusions are found, TRK inhibitors can be used. Recently, multiple studies demonstrated the efficacy of larotrectinib (Vitrakvi) in both adult and pediatric patients. Treatment with larotrectinib led to robust and durable responses among patients.

Since they are rare, Drilon highlights the importance for clinicians to learn how to test for 

[In terms of testing, we now know that] there are active agents like larotrectinib, and entrectinib for the treatment of 

 fusion-positive cancers. Testing to find these fusions is important. With this tumor agnostic approval, there are many ways to do this. In an ideal setting, we found that the optimal way to find these fusions is to do comprehensive next-generation sequencing of not only DNA, but also RNA. The latter maximizes the chance of finding these fusions because introns are very expensive, or there are other factors that lead to a lower likelihood of only finding the fusions on DNA.

 In our center, we've had a good experience with doing both to increase the number of fusions that we find. However, there are different practice environments. If you look at the guidelines that are out there, there are other tests that could be employed. That includes FISH, for example, but you need to do 3 different ones for the 3 different genes. Immunohistochemistry, which looks for expression as a surrogate for the presence of a fusion but doesn't actually find the fusion, but tests like those can be used to screen for these 

 fusions, if you're in a practice environment where you may not have insurance, or payer coverage for a more comprehensive testing.

Alexander Drilon, MD, discusses what to know when testing for NTRK gene fusions in patients with lung cancer.

Drilon Explains Testing for NTRK Gene Fusions

Edward B. Garon, MD, MS, professor of medicine, Geffen School of Medicine, Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, discusses his thoughts on the data from the phase 3 CANOPY-A study (NCT03447769) and what they mean for the future of canakinumab (Ilaris) for patients with non–small cell lung cancer (NSCLC).

CANOPY-A study evaluated treatment with adjuvant canakinumab in patients with completely resected NSCLC. Data presented at the 2022 ESMO showed that the study failed to meet its primary end point of disease-free survival.

While Garon notes he is unsure of other places where there could be therapeutic utility with the agent across cancer, he looks forward to the future exploration of canakinumab. Garon also anticipates that research will rely on additional preclinical evaluation to examine the role of inflammation in lung cancer and discusses the unmet needs in the NSCLC space.


In the end, the only sort of questions we can answer with this data are the ones that were asked. I think that this data is clear that in the setting of resected non–small cell lung cancer, this is not an attractive avenue. I don't know if that means that there are not other places where there could be therapeutic utility across cancer, but what I would say is that I would anticipate future exploration of this will rely on additional preclinical evaluation looking at the role of inflammation in lung cancer.

 After many years of somewhat unimpressive advances or minimal advances in the setting of early stage, non–small cell lung cancer, there's been a tremendous amount of exciting data over the last few months to years looking at the role of immune checkpoint inhibitors in this early stage setting, as well as data looking at signal transduction inhibitors, and osimertinib [Tagrisso]. Still, we recommend cisplatin based chemotherapy for patients which is a sort of chemotherapeutic approach associated with a fairly high degree of toxicity. Overall, the efficacy is less than we would hope for.

 I think that an emerging question is for what to do in patients who receive neoadjuvant chemoimmunotherapy and do not have a complete response. Very nice work as part of the Checkmate-816 study [NCT02998528] showed the importance of nivolumab [Opdivo] plus chemotherapy as a potential approach that could improve outcomes in early-stage disease. The data was impressive, particularly for patients who achieved a complete pathologic response, which was about a quarter of the patients. In the other patients, it's not clear what the value was. I think 1 of the challenges that we will have is, what to do in that group of patients after they've completed their chemoimmunotherapy?

Edward B. Garon, MD, MS, discusses data from the phase 3 CANOPY-A study and what they mean for the future of canakinumab for patients with non–small cell lung cancer.

Future Directions of Canakinumab and Unmet Needs in NSCLC

Joshua K. Sabari, MD, medical director of Kimmel Pavilion 12 at NYU Langone Health’s Perlmutter Cancer Center and assistant professor of medicine at NYU Grossman School of Medicine, explains his thoughts on the use of durvalumab (Imfinzi) for patients with extensive-stage small cell lung cancer (ES-SCLC).

(NCT03043872) were positive for patients with ES-SCLC when durvalumab was given in combination with tremelimumab (Imjudo) and given in conjunction with carboplatin or cisplatin and etoposide as it improved their overall survival. Moreover, there was an objective response rate (ORR) of 68% in patients in the CASPIAN trial compared with the addition of atezolizumab in the Impower133 trial (NCT02763579) with an ORR of 60%.

According to Sabari, when to use durvalumab in the frontline setting is ultimately up to the physician and the needs of the patient. He discusses that while trials have shown durvalumab’s positive results, there are still considerations depending on the individual situation. However, he does see that durvalumab is interchangeable in this setting.

 It is interesting. I think the use of durvalumab in the frontline setting is dependent on your practice preference. If you are using cisplatin in your frontline setting, which I often do not and often most practitioners the United States do not, but if you are in Europe and you're using cisplatin, I think using durvalumab regimen [in the frontline] makes more sense.

 If you're a practitioner that does the 6 cycles of therapy in the frontline setting, I think using durvalumab makes more sense [as well]. In my current practice, I am generally using 4 cycles of carboplatin and etoposide. Therefore, both regimens with durvalumab or atezolizumab are interchangeable in my experience.

Joshua K. Sabari, MD, discusses his use of durvalumab in the frontline setting for the treatment of patients with small-cell lung cancer and where he sees the role for the treatment.

Discussing When to Use Durvalumab in SCLC

Nathan Pennell, MD, PhD, vice chair of clinical research and director of lung cancer medical oncology at the Cleveland Clinic Taussig Cancer Center, discusses the importance of developing drugs based on resistance to previous treatments in patients with non–small cell lung cancer (NSCLC).

Pennell’s work on a phase 1 trial (NCT05241834) investigated LOXO-260, an agent designed based on drug resistance to the RET inhibitors selpercatinib (Retevmo) and pralsetinib (Gavreto) for patients with NSCLC and medullary thyroid cancer.

He says that this approach to drug development is based on studying real-world patients who initially respond but then progress on these agents due to resistance mutations. Doing biopsies on these patients for molecular profiling can show whether they have less expression of a gene or new mechanisms of resistance that are not present in untreated patients.

Pennell says that designing new drugs to fit unmet needs of first-generation targeted therapies is an exciting and important part of research, and having a new agent available for patients who relapse is a promising development.

 These are drugs that basically come directly from information from people with cancer who develop resistance. So real people with advanced lung cancer who are benefiting from targeted treatments, but then [whose] cancer gets worse anyway, have biopsies done, learn what's changed, and then based on that, they have designed drugs to overcome those elements of resistance—the new mutations.

Nathan Pennell, MD, PhD, discusses the importance of developing drugs based on resistance to previous treatments in patients with non–small cell lung cancer. 

LUNG CANCER

Latest News