Albert Rizzo, MD, is the chief medical officer of the American Lung Association.

Albert Rizzo, MD

Lungcast: Current Perspectives on Treatment of Small Cell Lung Cancer with Jacob Sands, MD

Small cell lung cancer (SCLC) remains one of the most formidable challenges in thoracic oncology. Accounting for roughly 15% of all lung cancers, SCLC is defined by its rapid growth, early metastatic potential, and high recurrence rates.

 While non–SCLC has seen transformative advances in targeted therapies and immunotherapy, SCLC has historically lagged behind, with chemotherapy and radiation long serving as the primary treatment backbone. Despite initial responses to therapy, outcomes have remained poor, with survival rates trailing far behind those seen in other lung cancer subtypes.

In recent years, however, a wave of research has begun to change this narrative. Advances in immunotherapy, novel chemotherapeutic agents, and innovative approaches such as bispecific antibodies and vaccines are reshaping treatment strategies. Landmark trials have introduced new standards of care, particularly in limited-stage disease, and ongoing studies continue to push the field toward more durable control and improved survival.

 The exploration of biomarkers and disease subtypes, once elusive in SCLC, is also beginning to show promise, raising the possibility of more personalized approaches to treatment.

, host Albert Rizzo, MD, is joined by Jacob Sands, MD, thoracic medical oncologist at Dana-Farber Cancer Institute and Associate Chief of the Lowe Center for Thoracic Oncology and Assistant Professor of Harvard Medical School, to discuss the evolving landscape of SCLC therapy. Sands, who also leads the small cell lung cancer clinical research program at Dana-Farber, shares insights into the latest therapeutic advances, the most promising investigational strategies, and why the outlook for patients with this historically intractable disease is finally beginning to brighten.

"There is more going on right now in the development of drugs for SCLC that looks encouraging, that looks exciting, than the culmination of everything up to this point so far. And the science is getting so fast that I think in the next decade ahead, we're going to see some very big advances in the field, and I'm just so optimistic looking forward now," Sands said. "If we talk in a year, there's going to be so much more to discuss."

Lungcast is a monthly respiratory news podcast series hosted by Albert Rizzo, MD, chief medical officer of the ALA, and produced by 

Editor's Note: Rizzo's disclosures include Pfizer, AstraZeneca, and Genentech. Sands' disclosures include Pfizer

AstraZeneca, Medtronic, Daiichi Sankyo/UCB Japan, Sanofi, Boehringer Ingelheim, PharmaMar, Guardant Health, AbbVie, Gilead Sciences, Lilly, and G1 Therapeutics.

Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. 

. 2021;7(1):3. Published 2021 Jan 14. doi:10.1038/s41572-020-00235-0

Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. 

Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. 

Videos

This episode of Lungcast features a discussion on emerging treatment approaches for SCLC.

Redefining Bronchiectasis Research and Management With First FDA Approval

 RX Review Special Report, Albert Rizzo, MD, and James Chalmers, MBChB, PhD, discuss how the August 2025 

 (marketed as Brinsupri), the first disease modifying therapy for bronchiectasis, may shift therapeutic goals in the field beyond exacerbation reduction and toward long-term preservation of pulmonary health.

Rizzo and Chalmers then discuss how trial endpoints in the field may evolve to focus on disease modification and slowing decline, and may include measures such as CT imaging and radiographic markers of airway damage, complementing traditional exacerbation rates and lung function outcomes.

Both experts reflect on the broader impact of this therapeutic advance. Chalmers anticipates increased recognition and diagnosis of bronchiectasis now that a targeted therapy is available, similar to the paradigm shift seen in interstitial lung disease after antifibrotic approvals. He stresses the need for collaboration across primary care, community pulmonology, and specialty centers to manage a condition that affects an estimated one million patients in the U.S. Importantly, he underscores that brensocatib should be viewed as one element of comprehensive care—alongside airway clearance, infection management, and evaluation of underlying causes—rather than a standalone solution.

"I think we're going to see a lot more attention to bronchiectasis. It's really been very much a Cinderella condition... and the availability of a new therapy, it gets people interested, it gives people a reason to diagnose it, because there's something powerful and effective that they can do about it," Chalmers said.

Part 1: Shifting Bronchiectasis Treatment Toward Disease Modification

Brensocatib Brings DPP1 Inhibition to the Bronchiectasis Field

Part 3: Understanding Brensocatib's Mechanism and Safety in Bronchiectasis

Part 4: Brensocatib's Place in Clinical Care of Bronchiectasis

Part 5: Redefining Bronchiectasis Research and Management With First FDA Approval

is a pulmonologist at ChristianaCare Pulmonary Associates at the ChristianaCare in Newark, Delaware, and clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia. Triple board certified in internal medicine, pulmonary, critical care and sleep medicine, he also served as the former Chief Medical Officer of the American Lung Association.

is a Clinical Professor (Teaching and Research) of Respiratory Research, Respiratory Medicine and Gastroenterology, at  University of Dundee, United Kingdom, where he also serves as Asthma and Lung UK Chair of Respiratory Research. He was a primary investigator on Insmed's ASPEN trial of brensocatib.

Editor's note: Rizzo's disclosures include Pfizer, AstraZeneca, and Genentech. Chalmer's disclosures include AstraZeneca, Boehringer Ingelheim, Genentech, Gilead, Grifols Biologicals, Insmed, Novartis, and Zambon.

Johnson V. FDA Approves First Bronchiectasis Therapy, Brensocatib, for Ages 12 and Up. 

https://www.hcplive.com/view/fda-approves-first-bronchiectasis-therapy-brensocatib-12-up

In this video, the last in a 5-part series, panelists discuss their future outlook on bronchiectasis management.

Brensocatib's Place in Clinical Care of Bronchiectasis

 RX Review Special Report, Albert Rizzo, MD, and James Chalmers, MBChB, PhD, discuss whether specific patient subgroups may benefit more from brensocatib, the 

 for bronchiectasis as of August 2025, marketed under the name Brinsupri. Chalmers explains that the ASPEN trial broadly included most phenotypes of bronchiectasis, with the exception of cystic fibrosis, active NTM infection, allergic bronchopulmonary aspergillosis, and severe immune deficiencies—conditions where neutrophil-targeting therapy may not be effective. For the vast majority of patients, including those with idiopathic, post-infective, or autoimmune-related disease, outcomes were consistent across subgroups, underscoring the central role of neutrophilic inflammation across bronchiectasis phenotypes.

Chalmers highlights that primary ciliary dyskinesia was well represented in ASPEN, making brensocatib a viable option for these patients, while cystic fibrosis remains excluded from the current approval. He notes that across sex, age, comorbidities, and underlying causes, treatment effects were strikingly consistent, reinforcing brensocatib’s broad applicability. However, he stresses that while this represents a major advance, the field still lacks predictive biomarkers that could guide precision use of anti-inflammatory therapies, a gap that remains an important research priority moving forward.

The discussion also touches on patients with overlapping COPD or asthma, which affected about 20% of the ASPEN population. Chalmers cautions that mislabeling is common, as many patients carry COPD or asthma diagnoses without objective confirmation, complicating interpretation of trial outcomes. While individuals labeled with COPD appeared to benefit in ASPEN, he emphasizes the need for properly designed studies in well-defined COPD or asthma cohorts to determine brensocatib’s true role in overlap disease. For now, he advises clinicians to focus primarily on the presence of clinically significant bronchiectasis when considering brensocatib, while recognizing that more data are needed to guide treatment in patients whose primary pathology is COPD or asthma.

In this video, the fourth in a 5-part series, panelists discuss who may benefit from brensocatib's approval.

Understanding Brensocatib's Mechanism and Safety in Bronchiectasis

 RX Review Special Report, Albert Rizzo, MD, and James Chalmers, MBChB, PhD, address safety considerations for brensocatib, marketed as Brinsupri, following its 

. Chalmers explains that both the phase 2 WILLOW trial and the large phase 3 ASPEN trial demonstrated a reassuring safety profile, with adverse events and serious events occurring at rates comparable to placebo. Importantly, despite targeting neutrophil activity, there was no observed increase in pneumonia or other infections—a critical finding given neutrophils’ role in host defense.

The most notable side effect seen in ASPEN was mild hyperkeratosis, occurring in roughly 3% of patients on the higher dose. Chalmers explains that this skin thickening resembles findings in the rare Papillon-Lefevre syndrome, where the DPP1 enzyme is absent, but emphasizes that in the trial cases were largely reversible, self-limiting, and only led to one discontinuation. He advises clinicians to counsel patients on this potential effect, noting that it may occur at variable times during therapy, even after several months of treatment.

Chalmers also outlines brensocatib’s novel mechanism of action as a first-in-class DPP1 inhibitor. By blocking DPP1 in the bone marrow, brensocatib prevents proteolytic enzymes like neutrophil elastase and cathepsin G from being activated and packaged into neutrophils. As a result, neutrophils migrate to the lung but are less capable of driving tissue injury, dampening inflammation without broadly impairing infection defense. This upstream, targeted approach, Chalmers notes, helps explain both its efficacy in reducing exacerbations and its favorable safety profile.

In this video, the third in a 5-part series, panelists discuss data from the phase 3 ASPEN trial.

Albert Rizzo, MD

Articles