Alecensa (alectinib)

After about 20 years of exciting improvements in treatment efficacy outcomes of advanced epidermal growth factor receptor (EGFR) mutant and anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC), also combined with a progressively better safety profile, from chemotherapy to new generation tyrosine kinase inhibitors (TKIs) (osimertinib, alectinib, brigatinib), the recent MARIPOSA and CROWN trials have changed this trend. The story would be easy and totally positive if these two innovative, amazing treatments were not associated with new peculiar features in safety profiles that must be discussed with patients, because they potentially affect their quality of life. When treating these patient populations, the peculiar safety profiles of amivantamab plu lazertinib and lorlatinib require a well-structured shared decision making, "where and when", both the high probability of a longer survival and the risk of worse quality of life must be well announced and explained to our patients before the shared final treatment choice.

A number of BM treatment-effective drugs have shown BM-preventive effects: In NSCLC, the EGFR-inhibitor osimertinib and ALK inhibitors like alectinib, brigatinib and lorlatinib lower the incidence of BM. In HER2-positive breast cancer, tucatinib and trastuzumab deruxtecan have preventive activity in patients without BM at baseline...Preventing BM requires a personalized, multidisciplinary approach, integrating tumor biology, individual risk assessment, and therapeutic advances. Secondary prevention in patients with BM is as vital as tertiary prevention, warranting prospective validation of preclinical concepts.

P2, N=920, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

ALK+ squamous and adenosquamous NSCLCs are rare, but biologically distinct, with inferior outcomes on 1L ALK TKI, highlighting the need for further research to develop effective treatment strategies.

Pralsetinib was added to osimertinib, resulting in a response lasting 4 months...After one month with alectinib only, osimertinib was added due to the progression, resulting in another response of more than two months. Upon progression with quadruple alterations (EGFR 19del, EGFR C797S, MET amplification, and RET fusions), cabozantinib-gefitinib combination was initiated, leading to rapid deterioration...At the same time, comprehensive genomic testing remains essential for therapeutic decision-making, with ctDNA analysis complementing tissue-based approaches. Notably, the FGFR3-TACC3 fusion may represent a novel resistance mechanism contributing to the limited efficacy of EGFR-TKI.

This case highlights the importance of genetic profiling and rapid and substantial efficacy of alectinib in treating ALK-positive PLADC, reinforcing the role of ALK inhibitors in managing severe cases and offering valuable insights for clinical strategies.

The patient demonstrates a remarkable clinical response to the ALK inhibitor alectinib...Additional analysis of pan-cancer RNA sequencing data from 5,725 tumors and genomic datasets comprising 6,977 melanomas demonstrates that such events are rare but potentially significant. This study highlights the need to consider alternative translation mechanisms and incorporate additional analytic filters, such as 5'/3' expression imbalance, to better capture actionable out-of-frame fusion events in the era of precision oncology.

Alectinib enhances the efficacy of GD2 CAR-T therapy in ALK-mutant NB primarily by attenuating PD-L1-mediated immune evasion, supporting its potential as a combinatorial therapeutic strategy.

P1, N=5, Completed, China Medical University Hospital | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Feb 2026

MTAP loss is frequent in oncogene-driven NSCLC, particularly in ALK-, RET-, and EGFR-altered subtypes. MTA-cooperative PRMT5 inhibition demonstrates broad activity in MTAP-deleted, oncogene-driven models and, and may enhance targeted therapy efficacy in selected settings.

P1/2, N=56, Recruiting, Joshua Palmer | Trial completion date: Jan 2027 --> Jun 2027 | Trial primary completion date: Jan 2026 --> Jun 2026

The patient was treated with CHOP chemotherapy, with alectinib added from the second cycle...Notably, neuron-specific enolase levels increased in parallel with disease progression. This case highlights diagnostic challenges related to an unusual clinical presentation and pathological overlap with other hematologic diseases.