Opus vs Sonnet: Publication Summaries

SKYSCRAPER-02C: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer in China.
Lu Shun. J Thorac Oncol. Read full article →

This phase 3 trial randomized Chinese patients with untreated extensive-stage small-cell lung cancer (ES-SCLC) without brain metastases (1:1) to tiragolumab 600 mg or placebo plus atezolizumab 1200 mg and carboplatin/etoposide (CE) for four cycles, followed by maintenance tiragolumab/placebo plus atezolizumab. In the primary analysis set (n=110), median PFS was 5.6 months with tiragolumab versus 5.4 months with placebo (unstratified HR = 0.65, 95% CI: 0.43–0.97). Median OS was 18.7 months versus 13.5 months, respectively (unstratified HR = 0.89, 95% CI: 0.56–1.40) at median follow-up of 26.7 months. RNA sequencing analysis identified that patients with NMF3 (SCLC-I-NE) or NMF4 (SCLC-I-nNE) molecular subtypes, and those with high T-effector and tumor-associated macrophage immune signatures, derived benefit from tiragolumab addition. No new safety signals were observed. Bottom line: While the global SKYSCRAPER-02 study did not meet statistical significance, this China cohort showed numerical PFS and OS improvements with tiragolumab addition, with biomarker analyses suggesting immune-inflamed subtypes may identify patients more likely to benefit from TIGIT-based therapy.

Anti-PD-1 antibody penpulimab plus chemotherapy for recurrent or metastatic nasopharyngeal carcinoma: a randomized, double-blind phase 3 study. Huang Shuang. Signal Transduct Target Ther. Read full article ->

This randomized, double-blind phase 3 trial evaluated penpulimab (anti-PD-1) plus chemotherapy versus placebo plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). A total of 291 patients were randomized 1:1 to receive penpulimab 200 mg (n=144) or placebo (n=147) plus cisplatin/carboplatin and gemcitabine every 3 weeks for 6 cycles, followed by maintenance penpulimab or placebo. At prespecified interim analysis, the primary endpoint of PFS was significantly improved with penpulimab versus placebo (median 9.63 vs 7.00 months; HR 0.45, 95% CI: 0.33-0.62, P<0.0001). OS data were immature with median OS not reached in either arm (HR 0.94; 95% CI: 0.63-1.40). Grade ≥3 treatment-related adverse events occurred in 89.0% versus 85.9% of patients, with the most common being neutropenia (56.2% vs 62.0%), leukopenia (54.1% vs 54.9%), and anemia (45.2% vs 38.7%). Grade ≥3 immune-related adverse events occurred in 4.1% of patients in the penpulimab arm. Bottom line: Penpulimab plus chemotherapy demonstrated a statistically significant PFS benefit over chemotherapy alone in first-line R/M NPC, though OS data remain immature.

Outcomes and Treatments of Patients With Non-Small Cell Lung Cancer Who Received Pembrolizumab. Rousseau Adrien. JAMA Oncol. Read full article →

This French nationwide, population-based retrospective cohort study evaluated outcomes and subsequent treatments in patients with advanced NSCLC who completed 2 years of pembrolizumab therapy. Among 41,498 patients who received frontline pembrolizumab, 1,480 patients with at least 6 months of follow-up who discontinued pembrolizumab at 2 years were analyzed (median age 63.0 years; 63.7% male; 41.6% received pembrolizumab monotherapy). After a median follow-up of 16 months post-landmark, the OS rate at 48 months was 76.9% (95% CI, 72.7%-81.3%), and the time to next treatment or death rate at 48 months after pembrolizumab discontinuation was 49.9% (95% CI, 45.3%-55.0%). Overall, 387 patients (26.1%) received subsequent therapy, with first treatments being chemotherapy (51.7%), radiotherapy (47.3%), and immunotherapy (1.0%). Immunotherapy rechallenge was rare, occurring in only 19 patients (0.1%) across all subsequent treatment lines. Twelve-month OS rates after initiating new treatment were 87.0% (95% CI, 81.6%-92.7%) for radiotherapy, 69.9% (95% CI, 61.1%-80.0%) for chemotherapy, and 61.4% (95% CI, 41.3%-91.4%) for immunotherapy. Bottom line: Long-term survivors with advanced NSCLC who complete 2 years of pembrolizumab demonstrate favorable survival outcomes, with approximately three-quarters alive at 4 years and immunotherapy rechallenge being uncommon in clinical practice.

Occupational exposure to asbestos-free talc and risk of respiratory cancers, including larynx, lung and mesothelioma: a systematic review and meta-analysis. Seyyedsalehi Monireh Sadat. J Thorac Oncol. Read full article →

This systematic review and meta-analysis examined the association between occupational exposure to asbestos-free talc and risk of lung cancer, mesothelioma, and laryngeal cancer. The analysis included 13 publications on lung cancer, 8 on mesothelioma, and 7 on laryngeal cancer. For lung cancer, meta-analysis of talc miners and millers showed a pooled RR of 1.13 (95% CI: 0.97-1.33), while workers in other industries had a pooled RR of 1.12 (95% CI: 0.79-1.57). No publication bias was detected (p = 0.45). No mesothelioma cases were reported among talc miners and millers, precluding meta-analysis. Laryngeal cancer showed no association with talc exposure (RR = 0.98, 95% CI: 0.58-1.57). Bottom line: Current evidence does not support an increased risk of lung cancer, mesothelioma, or laryngeal cancer among workers exposed to asbestos-free talc, though the authors note that future studies should better control for confounders, particularly tobacco smoking.

Phase 1b study of ABBV-368, tilsotolimod, budigalimab, and nab-paclitaxel in patients with recurrent/metastatic head and neck squamous cell carcinoma. Daste Amaury. J Immunother Cancer. Read full article →

This phase 1b, multicenter, open-label study (NCT04196283) evaluated ABBV-368 (anti-OX40 antibody) combined with tilsotolimod (TLR9 agonist), budigalimab (PD-1 inhibitor), and nab-paclitaxel in patients with recurrent/metastatic HNSCC. Thirty patients were enrolled across three arms: ABBV-368 plus tilsotolimod (n=16), ABBV-368 plus tilsotolimod and nab-paclitaxel (n=7), or the quadruple combination with budigalimab (n=7). Treatment was administered in 28-day cycles with intratumoral tilsotolimod and intravenous delivery of other agents. Any-grade treatment-related adverse events occurred in 80% of patients receiving ABBV-368. The doublet arm showed no responses; the triplet and quadruple arms each demonstrated one partial response, corresponding to an overall response rate of 14.3% in both. Biomarker analyses showed ABBV-368 plus tilsotolimod induced peripheral interferon-gamma pathway upregulation, Th1 cytokine production, and T-cell activation, which was not negatively impacted by nab-paclitaxel. Several patients achieved disease stabilization, but clinical responses were limited, with authors attributing this to inadequate priming to overcome prior therapy resistance mechanisms and an unfavorable tumor microenvironment. Bottom line: This novel quadruple immunotherapy-chemotherapy combination was well tolerated with evidence of pharmacodynamic activity, but demonstrated limited clinical responses (ORR 14.3%) in heavily pretreated R/M HNSCC patients.

Challenges and Controversies in the Diagnosis and Management of Thymic Epithelial Tumors from the Thymic Tumor Subcommittee of the International Association for the Study of Lung Cancer Rare Tumors Committee. Ardeshir-Larinani Fatemeh. J Thorac Oncol.

Summary: This IASLC consensus review addresses current challenges in the diagnosis and management of thymic epithelial tumors (TETs), including thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms. The authors outline diagnostic difficulties in distinguishing TETs from histologic mimickers and highlight the utility of immunohistochemical and molecular markers. Surgical considerations are explored, including the debate between thymomectomy versus complete thymectomy, optimal minimally invasive approaches, the role of lymph node dissection, and adjuvant therapy. The review discusses the evolving roles of immunotherapy and targeted therapy, acknowledging their potential while noting challenges including high rates of autoimmune disease recurrence and immune-related adverse events. Applications of artificial intelligence in diagnosis, target discovery, and prognostic modeling are identified as promising areas for future clinical integration. Bottom line: This expert consensus provides a comprehensive framework for addressing diagnostic and therapeutic controversies in thymic epithelial tumors, emphasizing the need for standardized approaches and careful consideration of autoimmune complications with immunotherapy.

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