This Week in Pulmonary — Oct 27, 2026
Generated Oct 27, 2026 · 10:48
The week's practice-changing Pulmonary research, summarized for clinicians.
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Tarlatamab-Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer.
Adding tarlatamab to durvalumab maintenance extended median overall survival from about 13 to 21 months in extensive-stage small-cell lung cancer, with frequent mostly low-grade cytokine release syndrome.
New England Journal of Medicine · 2026 · PubMed
This week’s papers
- 01
Tarlatamab-Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer.
Adding tarlatamab to durvalumab maintenance extended median overall survival from about 13 to 21 months in extensive-stage small-cell lung cancer, with frequent mostly low-grade cytokine release syndrome.
Pérol M et al. · New England Journal of Medicine · 2026
From the briefingThe headline is DeLLphi-305, led by Pérol, which randomized 563 patients with extensive-stage small-cell lung cancer who had not progressed after initial chemoimmunotherapy to maintenance with the DLL3-directed bispecific T-cell engager tarlatamab plus durvalumab, or durvalumab alone [1]. At this interim analysis, median overall survival was about 21 months with the combination versus just under 13 months with durvalumab, a reduction in the risk of death of nearly sixty percent, and progression-free survival rose from under two months to more than seven. The price is toxicity: severe adverse events were somewhat more frequent, and cytokine release syndrome, mostly grade 1 or 2, occurred in nearly half of patients on the combination. This is a single open-label trial at interim, but an effect of this size in a disease where maintenance has changed little is likely to reshape the first-line conversation.
If you only have time for one paper this week, make it the DeLLphi-305 trial of tarlatamab plus durvalumab maintenance [1]. It reopens a question that had seemed settled in extensive-stage small-cell lung cancer, showing that maintenance therapy can deliver a survival gain of this magnitude in one of the deadliest thoracic cancers.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 02
Divarasib as Compared with Sotorasib or Adagrasib in KRAS G12C-Mutated NSCLC.
In previously treated KRAS G12C-mutated lung cancer, divarasib improved progression-free and overall survival over sotorasib or adagrasib and caused fewer severe treatment-related adverse events.
Skoulidis F et al. · New England Journal of Medicine · 2026
From the briefingIn KRAS G12C-mutated non-small-cell lung cancer, Skoulidis and colleagues compared the next-generation inhibitor divarasib head-to-head with sotorasib or adagrasib in 338 previously treated patients [2]. Divarasib extended median progression-free survival from under six months to almost ten, extended median overall survival by nearly six months, and nearly doubled the confirmed response rate, while causing fewer serious treatment-related adverse events. Note that the control arm was overwhelmingly sotorasib, so the comparison with adagrasib rests on few patients.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 03
Osimertinib-Savolitinib in Advanced NSCLC after Progression during EGFR-TKI Therapy.
For EGFR-mutated lung cancer with MET overexpression or amplification after osimertinib, adding savolitinib beat platinum-pemetrexed for both progression-free and overall survival, with similar severe toxicity rates.
Lu S et al. · New England Journal of Medicine · 2026
From the briefingRounding out this group, the SAFFRON trial led by Lu addressed MET-driven resistance after osimertinib [3]. Among patients with MET overexpression or amplification, adding savolitinib to continued osimertinib roughly cut the risk of progression in half compared with platinum-pemetrexed, and also improved overall survival at final analysis, with one-year survival of about 70 percent versus about 53 percent. Peripheral edema affected about half of patients, and severe adverse events were similar between arms. Of note, fewer than one in five screened patients was eligible, underscoring that this benefit depends on biomarker testing at progression.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 04
Izalontamab brengitecan versus platinum-based chemotherapy in EGFR-mutated advanced non-squamous non-small-cell lung cancer after progression on third-generation EGFR tyrosine kinase inhibitors (PANKU-Lung01): a multicentre, randomised, open-label, phase 3 trial in China.
The EGFR-HER3 bispecific antibody-drug conjugate izalontamab brengitecan roughly doubled progression-free survival versus chemotherapy after third-generation EGFR inhibitors, but with more severe haematological toxicity.
Hong S et al. · The Lancet · 2026
From the briefingIn PANKU-Lung01, led by Hong, the first-in-class EGFR-HER3 bispecific conjugate izalontamab brengitecan roughly doubled median progression-free survival, from under six months to about eleven, in 432 randomized patients [4]. But severe treatment-related adverse events, mainly haematological, were clearly more frequent than with chemotherapy, affecting nearly four in five patients, and interstitial lung disease was reported in two patients.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 05
Ruzaltatug rezetecan versus chemotherapy for EGFR-mutated advanced non-small-cell lung cancer progressing after EGFR tyrosine kinase inhibitor therapy (HERON-Lung01): interim analysis of a randomised, open-label, phase 3 trial in China.
The HER3-directed conjugate ruzaltatug rezetecan lengthened median progression-free survival from about five to eight months versus chemotherapy in EGFR inhibitor-resistant lung cancer, with comparable severe toxicity.
Xu CR et al. · The Lancet · 2026
From the briefingHERON-Lung01, led by Xu, tested the HER3-directed conjugate ruzaltatug rezetecan in 498 patients and found a more modest gain, median progression-free survival of about eight months versus five, with severe treatment-related toxicity similar to chemotherapy [5]. Read alongside SAFFRON, these trials suggest the post-osimertinib setting is becoming crowded with chemotherapy-beating options, though none of these three trials compared active agents with each other, both conjugate trials report progression-free survival without mature survival data, and both enrolled only in China, which limits generalizability.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 06
Sacituzumab Tirumotecan plus Pembrolizumab in PD-L1-Negative Advanced NSCLC.
First-line sacituzumab tirumotecan plus pembrolizumab nearly tripled progression-free survival versus chemotherapy plus pembrolizumab in PD-L1-negative non-squamous lung cancer, though overall survival data remain immature.
Zhou F et al. · New England Journal of Medicine · 2026
From the briefingMoving to first-line therapy, the OptiTROP-Lung06 trial by Zhou, in the New England Journal of Medicine, randomized 455 patients with PD-L1-negative non-squamous non-small-cell lung cancer without targetable alterations to the TROP2-directed conjugate sacituzumab tirumotecan plus pembrolizumab or standard chemotherapy plus pembrolizumab [6]. Median progression-free survival nearly tripled, from under six months to fifteen, with fewer severe adverse events, though stomatitis was common. Response rates were nearly identical, so the advantage lies in durability, and with follow-up under ten months and overall survival immature, this is promising but not yet definitive evidence for replacing chemotherapy in this group.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 07
Rituximab vs Azathioprine for Eosinophilic Granulomatosis With Polyangiitis Maintenance Therapy: A Randomized Clinical Trial.
In a double-blind trial of 98 patients with EGPA in remission, rituximab maintenance was not superior to azathioprine for remission duration and roughly doubled severe infections.
Puéchal X et al. · JAMA · 2026
From the briefingIn JAMA, Puéchal and colleagues reported a double-blind, double-dummy French trial of 98 patients with eosinophilic granulomatosis with polyangiitis in recent remission, comparing rituximab with azathioprine maintenance [7]. Rituximab was not superior: time in remission on low-dose prednisone was essentially the same, about 91 versus 96 weeks, and relapse rates and asthma or sinus exacerbations did not differ meaningfully. Meanwhile, severe infections were nearly twice as common with rituximab, largely driven by COVID-19 during the pandemic era of enrollment. The trial was modest in size, but it offers no support for preferring rituximab over azathioprine for maintenance in this disease.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 08
Real-World Impact of Mepolizumab in COPD in a US Commercial and Medicare Claims Database.
In an uncontrolled before-and-after claims analysis, starting mepolizumab for COPD was associated with about 41 percent fewer moderate or severe exacerbations and less oral steroid use.
Panettieri RA et al. · International Journal of Chronic Obstructive Pulmonary Disease · 2026
From the briefingIn COPD, Panettieri and colleagues, in the International Journal of Chronic Obstructive Pulmonary Disease, examined commercial and Medicare claims for 470 patients with a year of data before and after starting mepolizumab, before its approval for COPD in the United States [8]. Moderate or severe exacerbations fell by about 41 percent, with reductions in oral steroid bursts and COPD-related hospital and emergency visits. This is a manufacturer-associated, uncontrolled before-and-after analysis, so regression to the mean and selection of patients started on treatment after a bad year likely inflate the effect; it is reassuring real-world support for the randomized data, not independent proof.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 09
Cavitary status and differential treatment response in refractory or severe Mycobacterium avium complex pulmonary disease: Amikacin liposome inhalation suspension versus intravenous amikacin.
Inhaled liposomal and intravenous amikacin achieved similar overall culture conversion in refractory MAC lung disease, but a significant interaction suggested relative benefit may differ by cavitary status.
Hayashi M et al. · Respiratory Medicine · 2026
From the briefingIn Respiratory Medicine, Hayashi and colleagues reviewed 57 Japanese patients with refractory or severe Mycobacterium avium complex lung disease intensified with either amikacin liposome inhalation suspension or intravenous amikacin [9]. Overall six-month culture conversion did not differ significantly, at roughly half of patients in each group, but weighted analysis found a significant interaction with cavitary disease: point estimates favoured the inhaled formulation in non-cavitary disease and intravenous amikacin in cavitary disease, especially upper-lobe cavities. Neither subgroup estimate was itself significant, and the authors explicitly frame this as hypothesis-generating.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 10
Low end-tidal carbon dioxide identifies high-severity pulmonary embolism and shock-level haemodynamics.
Nasal capnography end-tidal carbon dioxide was lower in higher-risk pulmonary embolism, and values below 20 mmHg were associated with shock-level haemodynamics in normotensive intermediate-high-risk patients.
Greenspon LW et al. · ERJ Open Research · 2026
From the briefingFinally, in ERJ Open Research, Greenspon and colleagues prospectively measured end-tidal carbon dioxide by nasal capnography in 62 patients with acute pulmonary embolism [10]. Values were substantially lower in higher-risk patients by European Society of Cardiology categories and in those referred for catheter-directed therapy, and a value below 20 millimetres of mercury was associated with shock-level haemodynamics among normotensive intermediate-high-risk patients. This is a small single-cohort study without outcome validation, but it points to a cheap, non-invasive signal of hidden physiological severity.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
The full briefing
This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.
Welcome to This Week in Pulmonary. This week we're covering 10 notable papers spanning a wave of phase 3 thoracic oncology trials, eosinophilic airway and vasculitic disease, and practical questions in infection and acute pulmonary embolism. Let's dive in.
Thoracic oncology dominates the week, and the first cluster of trials, all in the New England Journal of Medicine, shows targeted and immune-redirecting therapies outperforming current standards in small-cell lung cancer and in molecularly defined non-small-cell lung cancer. The headline is DeLLphi-305, led by Pérol, which randomized 563 patients with extensive-stage small-cell lung cancer who had not progressed after initial chemoimmunotherapy to maintenance with the DLL3-directed bispecific T-cell engager tarlatamab plus durvalumab, or durvalumab alone [1]. At this interim analysis, median overall survival was about 21 months with the combination versus just under 13 months with durvalumab, a reduction in the risk of death of nearly sixty percent, and progression-free survival rose from under two months to more than seven. The price is toxicity: severe adverse events were somewhat more frequent, and cytokine release syndrome, mostly grade 1 or 2, occurred in nearly half of patients on the combination. This is a single open-label trial at interim, but an effect of this size in a disease where maintenance has changed little is likely to reshape the first-line conversation. In KRAS G12C-mutated non-small-cell lung cancer, Skoulidis and colleagues compared the next-generation inhibitor divarasib head-to-head with sotorasib or adagrasib in 338 previously treated patients [2]. Divarasib extended median progression-free survival from under six months to almost ten, extended median overall survival by nearly six months, and nearly doubled the confirmed response rate, while causing fewer serious treatment-related adverse events. Note that the control arm was overwhelmingly sotorasib, so the comparison with adagrasib rests on few patients. Rounding out this group, the SAFFRON trial led by Lu addressed MET-driven resistance after osimertinib [3]. Among patients with MET overexpression or amplification, adding savolitinib to continued osimertinib roughly cut the risk of progression in half compared with platinum-pemetrexed, and also improved overall survival at final analysis, with one-year survival of about 70 percent versus about 53 percent. Peripheral edema affected about half of patients, and severe adverse events were similar between arms. Of note, fewer than one in five screened patients was eligible, underscoring that this benefit depends on biomarker testing at progression.
The second oncology thread is the rise of antibody-drug conjugates, and here three trials converge on the same setting while a fourth moves the class into first-line therapy. Two Lancet trials, both conducted in China, tested new conjugates against platinum-pemetrexed in EGFR-mutated non-squamous disease after tyrosine kinase inhibitor failure. In PANKU-Lung01, led by Hong, the first-in-class EGFR-HER3 bispecific conjugate izalontamab brengitecan roughly doubled median progression-free survival, from under six months to about eleven, in 432 randomized patients [4]. But severe treatment-related adverse events, mainly haematological, were clearly more frequent than with chemotherapy, affecting nearly four in five patients, and interstitial lung disease was reported in two patients. HERON-Lung01, led by Xu, tested the HER3-directed conjugate ruzaltatug rezetecan in 498 patients and found a more modest gain, median progression-free survival of about eight months versus five, with severe treatment-related toxicity similar to chemotherapy [5]. Read alongside SAFFRON, these trials suggest the post-osimertinib setting is becoming crowded with chemotherapy-beating options, though none of these three trials compared active agents with each other, both conjugate trials report progression-free survival without mature survival data, and both enrolled only in China, which limits generalizability. Moving to first-line therapy, the OptiTROP-Lung06 trial by Zhou, in the New England Journal of Medicine, randomized 455 patients with PD-L1-negative non-squamous non-small-cell lung cancer without targetable alterations to the TROP2-directed conjugate sacituzumab tirumotecan plus pembrolizumab or standard chemotherapy plus pembrolizumab [6]. Median progression-free survival nearly tripled, from under six months to fifteen, with fewer severe adverse events, though stomatitis was common. Response rates were nearly identical, so the advantage lies in durability, and with follow-up under ten months and overall survival immature, this is promising but not yet definitive evidence for replacing chemotherapy in this group.
Turning to eosinophilic disease, two papers offer a reminder that biologic enthusiasm needs testing against conventional options and rigorous designs. In JAMA, Puéchal and colleagues reported a double-blind, double-dummy French trial of 98 patients with eosinophilic granulomatosis with polyangiitis in recent remission, comparing rituximab with azathioprine maintenance [7]. Rituximab was not superior: time in remission on low-dose prednisone was essentially the same, about 91 versus 96 weeks, and relapse rates and asthma or sinus exacerbations did not differ meaningfully. Meanwhile, severe infections were nearly twice as common with rituximab, largely driven by COVID-19 during the pandemic era of enrollment. The trial was modest in size, but it offers no support for preferring rituximab over azathioprine for maintenance in this disease. In COPD, Panettieri and colleagues, in the International Journal of Chronic Obstructive Pulmonary Disease, examined commercial and Medicare claims for 470 patients with a year of data before and after starting mepolizumab, before its approval for COPD in the United States [8]. Moderate or severe exacerbations fell by about 41 percent, with reductions in oral steroid bursts and COPD-related hospital and emergency visits. This is a manufacturer-associated, uncontrolled before-and-after analysis, so regression to the mean and selection of patients started on treatment after a bad year likely inflate the effect; it is reassuring real-world support for the randomized data, not independent proof.
Two smaller studies address everyday decisions at the bedside, one in mycobacterial infection and one in acute pulmonary embolism. In Respiratory Medicine, Hayashi and colleagues reviewed 57 Japanese patients with refractory or severe Mycobacterium avium complex lung disease intensified with either amikacin liposome inhalation suspension or intravenous amikacin [9]. Overall six-month culture conversion did not differ significantly, at roughly half of patients in each group, but weighted analysis found a significant interaction with cavitary disease: point estimates favoured the inhaled formulation in non-cavitary disease and intravenous amikacin in cavitary disease, especially upper-lobe cavities. Neither subgroup estimate was itself significant, and the authors explicitly frame this as hypothesis-generating. Finally, in ERJ Open Research, Greenspon and colleagues prospectively measured end-tidal carbon dioxide by nasal capnography in 62 patients with acute pulmonary embolism [10]. Values were substantially lower in higher-risk patients by European Society of Cardiology categories and in those referred for catheter-directed therapy, and a value below 20 millimetres of mercury was associated with shock-level haemodynamics among normotensive intermediate-high-risk patients. This is a small single-cohort study without outcome validation, but it points to a cheap, non-invasive signal of hidden physiological severity.
If you only have time for one paper this week, make it the DeLLphi-305 trial of tarlatamab plus durvalumab maintenance [1]. It reopens a question that had seemed settled in extensive-stage small-cell lung cancer, showing that maintenance therapy can deliver a survival gain of this magnitude in one of the deadliest thoracic cancers.
Here is what this week's evidence adds up to in Pulmonary. First, a single open-label phase 3 trial shows tarlatamab-based maintenance substantially prolongs survival in extensive-stage small-cell lung cancer, at the cost of frequent, mostly low-grade cytokine release syndrome; longer follow-up is still needed. Second, in EGFR-mutated disease after osimertinib, biomarker-selected savolitinib and two antibody-drug conjugates each outperform platinum chemotherapy, but without head-to-head comparisons, and with survival data still immature for the conjugates, sequencing remains unsettled. Third, antibody-drug conjugates are moving into first-line PD-L1-negative disease and divarasib is now superior to first-generation KRAS G12C inhibitors, both on progression-free survival with early survival signals. Fourth, a well-designed randomized trial finds rituximab no better than azathioprine for EGPA maintenance and more infection-prone, while real-world mepolizumab data in COPD are supportive but uncontrolled. Fifth, end-tidal carbon dioxide in pulmonary embolism and cavity-guided amikacin selection in MAC disease are intriguing but early, single-cohort signals awaiting validation.
That's your roundup for This Week in Pulmonary. The full transcript and references are available on the episode page. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.
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