ROS1 positive

P2, N=27, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

P=N/A, N=97, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | Trial completion date: Mar 2027 --> Nov 2026 | Trial primary completion date: Mar 2027 --> Nov 2026

The patient received treatment with crizotinib and entrectinib successively. No new severe drug-related adverse events were observed. This case suggests that in patients with ROS1 fusion-positive nonsmall cell lung cancer who have experienced prior ROS1-tyrosine kinase inhibitor treatment failure and concomitant severe renal insufficiency, repotrectinib may represent a potential and tolerable treatment option when fully assessing clinical risks and ensuring close monitoring.

103 patients (95.4%) received ≥1 line of systemic anticancer therapy (SACT), of which 65 (63.1%) received first-line targeted therapy, mostly crizotinib monotherapy (n = 45) or crizotinib-based regimens (n = 10), with a median (95% CI) rwPFS and OS of 14.0 (8.3-19.8) and 47.9 (27.3-not estimable) months, respectively...Results from this study indicated a tendency for longer survival using currently available ROS1-targeted versus non-targeted therapy for patients with ROS1-positive advanced NSCLC. Nevertheless, survival outcomes were limited, highlighting the importance of more effective emerging treatments for ROS1-positive disease.

She was initiated on crizotinib, which led to a remarkable clinical response and tumor regression. Absolute diagnosis of pleural neoplasia can be daunting because of nonspecific imaging and cytology findings, more so if the pathology is in the fibrotic pleura. Pleural cryobiopsy, which employs a semirigid thoracoscope, makes room for larger and better-preserved tissue samples, enhancing the diagnostic yield in complicated scenarios like ours.

P3, N=71, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Sep 2033 --> Jun 2030 | Trial primary completion date: Aug 2032 --> Dec 2026

ROS1 IHC exhibited staining in cases harboring ALK, EGFR, and KRAS mutations, including one case with concurrent EGFR and ROS1 alterations. The ROS1 SP384 clone demonstrated 71.43% sensitivity and 84.97% specificity, with a negative predictive value of 99.3%. ROS1 IHC is a valuable screening modality for molecular alterations. FISH validation is recommended, and discordant cases may require NGS or RT-PCR for rare mutations or unidentified fusion partners.

The last follow-up in August 2025 showed the patient remained in good survival status. This case highlights a novel strategy of neoadjuvant targeted downstaging followed by surgical resection for small-lesion, highly invasive NSCLC, as well as the potential value of integrating postoperative Chinese-Western medicine management for long-term survival and treatment tolerance.

We found progressive arthropathy, mostly painless, in one or more joints or intervertebral spaces of patients receiving crizotinib for NSCLC.

Multiple ROS1 tyrosine kinase inhibitors (TKIs)-from crizotinib to newer agents such as entrectinib, lorlatinib, repotrectinib, taletrectinib, and the highly selective zidesamtinib-have improved systemic and intracranial outcomes, although resistance remains inevitable and biologically diverse, involving both on-target kinase mutations and off-target mechanisms...Pemetrexed-based chemotherapy remains an effective option, whereas immune checkpoint inhibitors provide limited benefit...Looking ahead, priorities include optimizing sequencing strategies, evaluating perioperative targeted approaches, and incorporating genomic monitoring to anticipate resistance. These advances are reshaping the natural history of ROS1-rearranged NSCLC and supporting a more durable, precision-driven treatment paradigm.

In ROS1-positive NSCLC patients, taletrectinib has been effective and well tolerated, as evidenced by early clinical trials, including those that are resistant to crizotinib. It demonstrates potential for disease control, as it has excellent oral absorption and is able to combat the spread of neurological disorders. Taletrectinib is emerging as a promising candidate for enhancing the outcomes of patients with ROS1-positive lung cancer as the treatment landscape for this disease continues to evolve.

In this study, in addition to the induction of apoptosis, the use of PARPis (olaparib and niraparib) as maintenance therapies inhibited cell proliferation by causing cellular senescence to exert potent anticancer effects on Capan-1 (BRCA mutated) and PANC-1 (BRCA wild-type) cells...The inhibition of Bcl-2 through the sequence-dependent combination of navitoclax enhanced the anticancer effects of PARPis by removing senescent cells. Collectively, data from our study demonstrate that the clinical application of PARPis as maintenance therapy could be achieved through the induction of cellular senescence. Furthermore, sequence-dependent combination with senescence-targeting drugs can potentiate pancreatic cancer treatment effects of PARPis regardless of the BRCA status.