Jonathan W. Goldman, MD, is a professor of medicine in the Hematology/Oncology Division, director of Clinical Trials in Thoracic Oncology, and associate director of Early Drug Development at UCLA Medical Center in California.

Jonathan W. Goldman, MD, discusses the role of telisotuzumab vedotin for the treatment of locally advanced or metastatic NSCLC with c-MET overexpression.

Dr Goldman on the Telisotuzumab Vedotin Outcomes in Advanced NSCLC With c-MET Overexpression by Prior Therapy

“The primary end point of LUMINOSITY was the objective response rate in the c-MET–high group. It was 35%, so it was meaningfully superior to 2 other FDA-approved agents in the second-line setting.”

Jonathan W. Goldman, MD, a professor of medicine in the Hematology/Oncology Division, director of Clinical Trials in Thoracic Oncology, and associate director of Early Drug Development at UCLA Medical Center, discusses the efficacy of telisotuzumab vedotin-tllv (Emrelis) in the treatment of patients with nonsquamous, 

 wild-type, advanced non–small cell lung cancer (NSCLC) with c-MET overexpression, based on prior therapy, in the phase 2 LUMINOSITY trial (NCT03539536).

FDA granted accelerated approval to telisotuzumab vedotin

 for the treatment of adult patients with locally advanced or metastatic, nonsquamous NSCLC who harbor high c-MET protein overexpression and have previously received systemic therapy. The regulatory decision was based on data from the LUMINOSITY trial; findings supporting the approval revealed that patients with high c-MET protein overexpression treated with the agent (n = 84) experienced an overall response rate (ORR) of 35% (95% CI, 24%-46%), of which all responses were partial responses. Additionally, the median duration of response (DOR) was 7.2 months (95% CI, 4.2-12), with 6- and 12-month DOR rates of 59% and 21%, respectively.

The study’s primary end point was ORR, Goldman began. Among patients with high c-MET protein expression, the ORR was meaningfully superior vs historical data for other agents that have been FDA-approved in the second-line setting, he noted.

In an another analysis of data from LUMINOSITY presented at the 

, findings patients with high c-MET protein overexpression previously treated with platinum chemotherapy alone (n = 81) experienced an ORR of 34.6%, whereas those previously treated with platinum and an immune checkpoint inhibitor (n = 67) achieved an ORR of 32.8%. Patients with intermediate c-MET protein overexpression had similar response outcomes irrespective of prior therapy.

Regarding safety, the integration of antibody-drug conjugates with MMAE payloads into clinical practice has led to novel toxicities associated with this class of agents, Goldman said. Ocular toxicities represent 1 of these adverse effects (AEs), he continued. However, instances of these AEs have been low and generally mild with telisotuzumab vedotin, he noted. Peripheral neuropathy is another AE of concern, but Goldman explained that unlike taxane neuropathy, he has found peripheral neuropathy to be reversible with telisotuzumab vedotin. The emergence of neuropathy can also stem from a longer-term duration on treatment, Goldman added.

The open-label, single-arm study included patients 18 years of age or older with locally advanced or metastatic nonsquamous and 

 wild-type NSCLC, including high c-MET overexpression per immunohistochemistry testing. Those on the study were required to have experienced disease progression after or intolerance to systemic cytotoxic therapy, previously received an immune checkpoint inhibitor with or without chemotherapy, and targeted anticancer therapies if indicated. Specifically, no more than 2 prior lines of systemic therapy were allowed in the locally advanced or metastatic setting, which included 1 line of chemotherapy. Multiple prior lines of TKIs were allowed as 1 line of treatment. Of note, patients were also required to have an ECOG performance status of 0 or 1.

Videos

Dr Goldman on the Efficacy of Telisotuzumab Vedotin in Advanced NSCLC With c-MET Overexpression

Jonathan W. Goldman, MD, hematologist and oncologist, UCLA Medical Center, discusses key takeaways from the phase 3 CASPIAN trial (NCT03043872) in patients with extensive-stage small cell lung cancer (ES-SCLC).

CASPIAN examined the use of durvalumab (Imfinzi) in combination with etoposide and either carboplatin or cisplatin, or durvalumab and chemotherapy with the addition of tremelimumab vs chemotherapy alone in the frontline treatment of patients with ES-SCLC.

Results from the study showed no overall survival benefit with the 4-drug regimen. However, a median OS benefit of approximately 2.5 months was observed with the 3-drug regimen vs chemotherapy alone, translating to a hazard ratio of 0.75. The regimens were also found to have favorable safety profiles, according to Goldman. The addition of immunotherapy to the chemotherapy backbone did not come at the cost of significant toxicity.

Some immunotherapy-related toxicities were observed in the durvalumab arm, but most were manageable endocrine disorders, Goldman says. The OS data, along with the quality-of-life benefit of delayed worsening of symptoms, support durvalumab plus chemotherapy as a standard-of-care treatment in the first-line setting for this population, Goldman concludes.

Jonathan W. Goldman, MD, discusses key takeaways from the phase 3 CASPIAN trial in patients with extensive-stage small cell lung cancer.


Dr. Goldman on Key Takeaways From the CASPIAN Trial in Frontline ES-SCLC

Jonathan W. Goldman, MD, health sciences clinical instructor, Department of Medicine, and Hematology/Oncology member, Jonsson Comprehensive Cancer Center Signal Transduction and Therapeutics Program, UCLA, discusses the use of immunotherapy in patients with oncogene-driven non—small cell lung cancer (NSCLC).

Immunotherapy, either alone or in combination with chemotherapy, plays an important role in the treatment of patients with advanced nonsquamous and squamous NSCLC. However, the role of immunotherapy in oncogene-driven cancers, such as 

, is less apparent. While the benefit of immunotherapy alone in these subsets is limited, there may be benefit to chemoimmunotherapy for patients whose tumors harbor 

According to data from the phase III IMpower150 trial, a small subset of patients with

 fusions derived benefit from the addition of atezolizumab (Tecentriq) to carboplatin, paclitaxel, and bevacizumab (Avastin). Although the trial wasn’t powered to evaluate benefit in this population, there is enough evidence to consider it as an option after patients with these alterations have progressed through all available targeted therapies, concludes Goldman.

Jonathan W. Goldman, MD, health sciences clinical instructor, Department of Medicine, and Hematology/Oncology member, Jonsson Comprehensive Cancer Center Signal Transduction and Therapeutics Program, UCLA, discusses the use of immunotherapy in patients with oncogene-driven non–small cell lung cancer (NSCLC).

Dr. Goldman on the Use of Immunotherapy in Oncogene-Driven NSCLC

Jonathan W. Goldman, MD, health sciences clinical instructor, Department of Medicine, and Hematology/Oncology member, Jonsson Comprehensive Cancer Center Signal Transduction and Therapeutics Program, UCLA, discusses the impact of liquid biopsies in lung cancer.

Liquid biopsies have reduced the amount of time it takes to perform a biopsy and match patients with appropriate therapy, explains Goldman. If patients don't have tissue results when they come in for their initial evaluation, a blood test can provide potentially actionable results within a week. Additionally, blood tests are performed with next-generation sequencing, which accounts for 70 or more mutations at a time.

Currently, liquid biopsies are not as sensitive as standard tissue tests, says Goldman. While there is concern for false negatives with liquid biopsies, a positive result is a dependable result. Apart from diagnosis, liquid biopsies could also be used to assess resistance mutations, concludes Goldman.

Jonathan W. Goldman, discusses the impact of liquid biopsies in lung cancer.

Dr. Goldman on the Impact of Liquid Biopsies in Lung Cancer

Jonathan W. Goldman, MD, health sciences clinical instructor, Department of Medicine, and Hematology/Oncology member, Jonsson Comprehensive Cancer Center Signal Transduction and Therapeutics Program, UCLA, discusses targeted therapy options for patients with 

-mutated non—small cell lung cancer (NSCLC).

In April 2018, osimertinib (Tagrisso) was approved by the FDA for the first-line treatment of patients with metastatic NSCLC whose tumors harbor 

 exon 19 deletions or exon 21 L858R mutations.

Osimertinib is a highly effective oral TKI with limited adverse events, explains Goldman.

Similarly, alectinib (Alecensa) is a well-tolerated oral TKI that was approved by the FDA in November 2017 for the treatment of patients with 

Patients treated with alectinib can experience durable remissions, says Goldman.

 mutations are relatively rare, 2 oral inhibitors, crizotinib (Xalkori) and entrectinib (Rozlytrek), have been approved for the treatment of patients with 

Jonathan W. Goldman, MD, discusses targeted therapy options for patients with EGFR-, ALK-, and ROS1-mutated non–small cell lung cancer.

Jonathan W. Goldman, MD

Articles

Dr Goldman on the Efficacy of Telisotuzumab Vedotin in Advanced NSCLC With c-MET Overexpression

Dr. Goldman on Key Takeaways From the CASPIAN Trial in Frontline ES-SCLC

Dr. Goldman on the Use of Immunotherapy in Oncogene-Driven NSCLC

Dr. Goldman on the Impact of Liquid Biopsies in Lung Cancer

Dr. Goldman on Targeted Therapy Options for EGFR-, ALK-, and ROS1-Mutated NSCLC