Dr Singhi on Identifying Care Gaps and Unmet Needs in Early-Stage Lung Cancer

Eric Kumar Singhi, MD, assistant professor, Department of General Oncology, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses how oncologists are continuing to identify gaps in care and understand unmet needs in patients with small cell lung cancer (SCLC).

In recent years, Singhi says experts in the SCLC treatment field has gained a deeper understanding of unmet needs that exist for patients with this disease. Despite these advancements, there is still a need for more effective treatment strategies for patients with extensive-stage SCLC (ES-SCLC), Singhi emphasizes. In 2024, the most significant developments in the extensive-stage setting have been in subsequent lines of therapy, particularly with 

the phase 2 DeLLphi-301 trial (NCT05060016),

 he explains. Findings from this trial supported 

FDA approval of tarlatamab-dlle (Imdelltra)

 for the treatment of patients with ES-SCLC who have disease progression on or after platinum-based chemotherapy. Tarlatamab is a bispecific T-cell engager that binds to DLL3, which is often overexpressed in SCLC cells, as well as CD3 on T cells, enhancing T-cell activity against cancer, Singhi says.

In DeLLphi-301, tarlatamab generated a 40% (95% CI, 31%-51%) objective response rate in patients (n = 99) who had undergone 2 or more lines of prior therapy. This approval represents an important milestone, yet clinical trial enrollment is still recommended in the National Comprehensive Cancer Network Guidelines for patients with SCLC with progressive disease following first-line chemoimmunotherapy, he elucidates.

One key aspect of the DeLLphi-301 study was the per-protocol management of treatment-related toxicities, particularly cytokine release syndrome (CRS), Singhi continues. Fortunately, most cases of CRS were manageable and predictable, typically appearing during cycle 1, according to Singhi. Despite these adverse effects, tarlatamab has the potential to be practice-changing, he emphasizes. However, given the necessary hospital admissions for the first 2doses and the close monitoring requirements, integrating this treatment into routine practice presents logistical challenges, Singhi notes.

Further research is underway to explore tarlatamab’s role in treating patients with limited-stage SCLC, which could extend its benefits to an earlier disease setting, Singhi concludes.

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Eric Kumar Singhi, MD, discusses the identification of current care gaps and unmet needs in small cell lung cancer.

Dr Singhi on the Potential Benefit of the ADRIATIC Study Findings in LS-SCLC

Eric Kumar Singhi, MD, assistant professor, Department of General Oncology, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses unmet needs in the treatment of patients with small cell lung cancer (SCLC), highlighting how 

the phase 3 ADRIATIC study (NCT03703297) addressed

There have been several exciting updates in the management of SCLC, leading to significant improvements in patient care, Singhi begins. SCLC is known for its aggressive nature, with approximately two-thirds of patients presenting with extensive-stage disease at diagnosis and one-third of patients presenting with limited-stage disease confined to 1 side of the chest, he explains. For limited-stage SCLC (LS-SCLC), the standard of care has remained largely unchanged for nearly 4 decades, Singhi reports, adding that this treatment is challenging, requiring several weeks of therapy. Even after successful treatment, 5-year overall survival (OS) rates are still between 15% and 25%, indicating that most patients are not cured, he notes.

Improving clinical outcomes for patients with LS-SCLC has been challenging, Singhi expands. At the 

, the ADRIATIC study results were presented, he says. The study investigated durvalumab (Imfinzi) as consolidation treatment following concurrent chemoradiation for up to 2 years in patients with LS-SCLC. At a median follow-up of 37.2 months (range, 0.1-60.9), the findings were promising, showing a significant increase in OS with durvalumab (n = 264). The median OS extended from 33.4 months (95% CI, 25.5-39.9) with placebo (n = 266) to 55.9 months (95% CI, 37.3-not evaluable) with durvalumab.

When evaluating new treatments, toxicity is a critical concern, particularly with the combination of radiation and immunotherapy, Singhi expands. A key issue is pneumonitis, an inflammation of the lungs, according to Singhi. However, the ADRIATIC study showed that rates of grade 3 and 4 pneumonitis were only slightly higher with durvalumab compared with placebo, which is reassuring, he emphasizes. After a long period without significant advancements, it is encouraging to see progress in treatment for patients with LS-SCLC, Singhi concludes.

Eric Kumar Singhi, MD, discusses unmet needs in the management of small cell lung cancer, highlighting how the ADRIATIC study addressed these needs.

Dr Singhi on Areas of Interest in Metastatic Lung Cancer Research

Eric Kumar Singhi, MD, assistant professor, Department of General Oncology, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses potential areas of research interest in the treatment of patients with metastatic lung cancer.

A critical area of focus for patients with metastatic lung cancer is determining the next steps after progression on immunotherapy, specifically in the second-line setting, Singhi begins. Currently, docetaxel remains the standard of care (SOC) in this scenario, and challenges have arisen when trying to develop investigational treatments that outperform this drug, he explains. Recently, there has been significant interest in the development of antibody-drug conjugates (ADCs) for this purpose, according to Singhi. During the 2024 ASCO Annual Meeting, data from the phase 3 EVOKE-01 study (NCT05089734)—a trial examining the TROP2-directed ADC sacituzumab govitecan-hziy (Trodelvy) in patients with metastatic non–small cell lung cancer (NSCLC)—were presented. This trial compared sacituzumab govitecan with docetaxel in patients who had progressed following chemoradiotherapy, Singhi states. Although the trial did not meet its primary end point of overall survival, it showed a numerical improvement with sacituzumab govitecan vs docetaxel in patients who had not responded to prior immunotherapy.

This finding raises the question of whether oncologists are still in the process of identifying the ideal patient population for ADCs or whether additional biomarkers are needed to guide treatment decisions, he continues. Despite the excitement surrounding these emerging ADCs, they have yet to deliver a breakthrough response for patients in the second-line setting and beyond after progression on chemoimmunotherapy, Singhi emphasizes, adding that this indicates a need to explore alternative strategies.

One trial generating considerable anticipation is the phase 3 Pragmatica-Lung study (NCT05633602) comparing ramucirumab (Cyramza) plus pembrolizumab (Keytruda) with SOC treatments for patients with recurrent NSCLCafter immunotherapy, he explains. The potential for a response to immunotherapy with the addition of ramucirumab appears promising, and the results are eagerly awaited, Singhi concludes.

Eric Kumar Singhi, MD, discusses potential areas of research interest in the treatment of patients with metastatic lung cancer.

Eric K. Singhe, MD, of The University of Texas MD Anderson Cancer Center, discusses the journey of non–smell cell lung cancer treatment.

Dr Eric Singhi Navigates NSCLC Treatment and Management

Eric K. Singhi, MD, of The University of Texas MD Anderson Cancer Center, discusses the journey of non–smell cell lung cancer treatment through mentorship, advocacy, and more.

Singhi discussed how personal experiences have impacted his career and how he approaches treatment of patients with cancer in clinical practice. 

"What I learned from having a diagnosis of cancer in my family was the impact that it has not only on the person that has cancer, but on their family members, on their caregivers, on their loved ones," Singhi said. "[There is] the emotional toll, the physical toll, understanding the diagnosis, and patients and families are thrown immediately into a whole new world of language they don't understand—new tests, new labs, new scans, new treatments. How do they process that? How do they understand it?"

Singhi also touched how social media can be a double-edged sword, especially for health care professionals. 

"A lot of us post about all the accomplishments that we have—all the accomplishments and successes and success stories. Very rarely do you see that raw side of rejections of, you know, times where there were failures," Singhi said. "How do you turn those experiences into a more positive experience and how do you turn them into learning experiences?"

Singhi stressed that sometimes it's not just about the destination, highlighting it context with research and grant efforts in one's career, but it's about the journey being taken with them. 

"It's about the people that you meet, the connections that you make, and the skillset that you learn by just going through different opportunities," he explained. "We need to all be more open about not only the success stories that we have, but some of the failures and the challenges that we have and what we learn from them."

Eric K. Singhe, MD, of The University of Texas MD Anderson Cancer Center, discusses the journey of non–smell cell lung cancer treatment through mentorship, advocacy, and more. 

Eric K. Singhi, MD

Articles

Dr Singhi on Identifying Care Gaps and Unmet Needs in Early-Stage Lung Cancer

Dr Singhi on the Potential Benefit of the ADRIATIC Study Findings in LS-SCLC

Dr Singhi on Areas of Interest in Metastatic Lung Cancer Research

Dr Eric Singhi Navigates Advocacy, Mentorship, and More in NSCLC Management