Adjuvant alectinib in ALK-positive lung cancer

A 46-year-old teacher who never smoked has a chest CT scan for a cough that does not go away after a flu. The exam shows a 4.5 cm nodule in the left lower lobe. The biopsy confirms lung adenocarcinoma, and staging shows no disease outside the chest. She undergoes lobectomy with systematic lymph node removal. The final report shows a 4.5 cm tumor with two involved mediastinal lymph nodes, margins free. At the postoperative visit, the surgeon asks the oncologist whether it is worth requesting the molecular profile, since the tumor was completely removed. The scene is fictional and was written for teaching.

This text uses the case as a clinical reasoning scenario for students and health professionals. The topic is adjuvant alectinib in non-small cell lung cancer with ALK gene rearrangement, tested in the ALINA study. The focus is the sequence of decisions: when to test for ALK, who is a candidate, what the study actually showed, how to give the drug and what to monitor. It does not replace your institution's protocol or the decision of the multidisciplinary team. If you play the case of the day on NEXO, you will recognize the challenge: deciding with clues that arrive in sequence.

Key points

• ALK rearrangement is rare in early-stage disease, but it changes treatment after surgery, so testing needs to be considered already in the operated patient.
• In ALINA, alectinib for 2 years reduced recurrence and death compared with platinum chemotherapy, with a hazard ratio of 0.24 in stages II to IIIA.
• Overall survival was not yet mature in the primary analysis, so the demonstrated benefit is in preventing recurrence, not in cure.
• The FDA label indicates 600 mg orally twice a day with food, for 2 years, for tumors of 4 cm or more or with positive lymph nodes.
• Alectinib requires monitoring of liver, creatine phosphokinase, heart rate, lungs and contraception.
• The FDA approved the adjuvant indication on 04/18/2024, and the EMA committee gave a favorable opinion on 04/25/2024.

Why this is a reasoning scenario

Operated non-small cell lung cancer often comes back, even when surgery removes all visible tumor. For many years, the only option after surgery was platinum chemotherapy, with modest benefit (EMA assessment report, 2024). Historical data show limited gain in the general population and no survival advantage in stage IB tumors smaller than 4 cm (EMA assessment report, 2024). The arrival of targeted therapies changed the question. Now, the result of the tumor's molecular profile can define treatment after surgery (Hsu et al., 2024) (Jeon et al., 2025).

ALK rearrangement is one of these targets. It appears in 2 to 7 percent of early-stage tumors, versus about 19 percent in stage IV disease (Chen and Chaft, 2023). People who are ALK positive tend to be younger, nonsmokers or light smokers, with a more balanced distribution between men and women (Chen and Chaft, 2023). The teacher in the scene has the classic profile, but the profile alone is not enough to decide on testing. The post on signs, symptoms and history helps remind us that history guides suspicion, but does not replace the exam.

What the scene teaches

The scene trains six habits. The first is to request the molecular profile in the operated tumor, not only in metastatic disease. The second is to read the stage from the surgical specimen report. The third is to check whether the patient fits the study criteria. The fourth is to separate what the study showed from what it has not yet answered. The fifth is to give the right dose, with food, for the right length of time. The sixth is to plan monitoring for adverse effects from the first visit. The post on clinical decision-making reminds us that each exam needs to change a decision, and the ALK test here does.

What is not at stake

The text does not cover in detail adjuvant osimertinib for tumors with an EGFR mutation, which has another study and will be the subject of another text in this series. It also does not cover the treatment of ALK-positive metastatic disease or perioperative immunotherapy. The post about diagnostic uncertainty helps when the test result is slow and the team needs to decide what to do while waiting.

When to test for ALK in the operated patient

Testing the operated tumor

Selection for adjuvant alectinib depends on the presence of ALK positivity in the tumor tissue, detected by an approved test (Alecensa label of 08/2026). In ALINA, the rearrangement was identified by an FDA-approved local test or by central immunohistochemistry with the VENTANA ALK (D5F3) assay (Alecensa label of 08/2026). A 2025 review on the treatment of lung cancer notes that high-throughput sequencing (NGS) identifies several targets, among them EGFR, ALK, ROS1, BRAF, MET, RET and NTRK, and guides the choice of therapy (Jeon and colleagues, 2025). In early-stage disease, ordering only EGFR leaves out ALK and other targets.

The rarity of ALK and the lack of standardized tests in early-stage disease hampered adjuvant studies for years (Chen and Chaft, 2023). Large programs, such as the American cancer institute's ALCHEMIST, were created to test the resected tumor and refer patients to studies (Chen and Chaft, 2023). In a review on neoadjuvant targeted therapy, the authors note that studies were stopped for lack of recruitment, because ALK fusions are rare and were not yet tested routinely in early-stage disease (Kemper and colleagues, 2024).

Why the test also matters for immunotherapy

The ALK result changes more than one decision. Induction immunotherapy studies excluded tumors with EGFR or ALK alterations (Lavaud and colleagues, 2024). In the adjuvant atezolizumab study, there was no disease-free survival benefit in patients with EGFR or ALK alterations, and the FDA approved the drug only for tumors without these alterations (Houda and colleagues, 2024). Testing before choosing perioperative systemic therapy therefore avoids giving immunotherapy to those who are unlikely to benefit (Nohra and colleagues, 2026). The post about differential diagnosis shows how each clue changes the range of options.

Who is a candidate

The FDA label restricts the indication to tumors of 4 cm or more or with positive lymph nodes, after resection (Alecensa label of 08/2026). In the study, patients had stage IB disease with a tumor of 4 cm or more up to IIIA, according to the seventh edition of the staging system (Alecensa label of 08/2026). The EMA uses the expression high risk of recurrence, with reference to the study criteria (EMA assessment report, 2024) (Alecensa page on the EMA). The professor in the scene has a 4.5 cm tumor and involved mediastinal lymph nodes, so she fits the indication.

What ALINA tested

Study design

ALINA was a global, randomized, open-label study that compared alectinib with platinum-based chemotherapy after complete resection (Alecensa label of 08/2026). Randomization was 1 to 1 and stratified by race, Asian or non-Asian, and by stage, IB, II or IIIA (Alecensa label of 08/2026). Alectinib was given at a dose of 600 mg orally twice a day, for 2 years or until recurrence or unacceptable toxicity (Alecensa label of 08/2026). The number of patients with stage IB disease was limited to 25 percent, to ensure that at least 75 percent had stage II to IIIA disease (EMA assessment report, 2024).

The chemotherapy arm

Chemotherapy was given intravenously in 4 cycles of 21 days (Alecensa package insert, 08/2026). The regimens were cisplatin 75 mg/m² on day 1 with vinorelbine 25 mg/m² on days 1 and 8, cisplatin 75 mg/m² on day 1 with gemcitabine 1250 mg/m² on days 1 and 8, or cisplatin 75 mg/m² on day 1 with pemetrexed 500 mg/m² on day 1 (Alecensa package insert, 08/2026). Those who did not tolerate cisplatin received carboplatin with AUC 5 or 6 mg/mL/min in the same combinations (Alecensa package insert, 08/2026). This matters because the control was chemotherapy, not observation.

Outcomes

The primary outcome was investigator-assessed disease-free survival, tested first in stages II to IIIA and then in the whole randomized population (Alecensa package insert, 08/2026). Disease-free survival counted the first recurrence, a new primary lung cancer or death from any cause (Alecensa package insert, 08/2026). Overall survival was a secondary outcome, and time to central nervous system recurrence was an exploratory outcome (EMA assessment report, 2024) (Santoni-Rugiu and colleagues, 2025). The post about diagnostic pause helps you ask the right question before reading the result: which outcome was measured and which was not.

Who was enrolled

A total of 257 patients were randomized, 130 to alectinib and 127 to chemotherapy (Alecensa package insert, 08/2026). Median age was 56 years, 52 percent were women, 56 percent were Asian and 60 percent had never smoked (Alecensa package insert, 08/2026). Ten percent had stage IB, 35 percent stage II and 55 percent stage IIIA (Alecensa package insert, 08/2026). N2 lymph node involvement appeared in 49.2 percent of the alectinib arm and in 52 percent of the chemotherapy arm (Santoni-Rugiu and colleagues, 2025). The first patient was randomized on August 16, 2018, the last on December 8, 2021, and the data cutoff was June 26, 2023 (EMA assessment report, 2024).

What ALINA showed

The main ALINA paper is not available in open full text. Therefore, the numbers below come from the FDA package insert, the EMA assessment report and full-text reviews that read the study.

Disease-free survival

In stages II to IIIA, there were 14 events in 116 patients on alectinib, 12 percent, versus 45 in 115 on chemotherapy, 39 percent (Alecensa package insert, 08/2026). The hazard ratio was 0.24, with a 95 percent confidence interval of 0.13 to 0.45 (Alecensa package insert, 08/2026). In the whole population, there were 15 events in 130 versus 50 in 127, with a hazard ratio of 0.24 and an interval of 0.13 to 0.43 (Alecensa package insert, 08/2026). The median was not reached with alectinib and was 41.3 months with chemotherapy in the total population (Alecensa package insert, 08/2026). At 2 years, 93.8 percent of patients on alectinib were disease-free, versus 63.0 percent on chemotherapy (Yin and Antonoff, 2025).

The table summarizes the main numbers.

Measure	Alectinib	Chemotherapy	Source
Events, stages II to IIIA	14 of 116	45 of 115	(Alecensa package insert, 08/2026)
Hazard ratio, stages II to IIIA	0.24 (0.13 to 0.45)	Reference	(Alecensa package insert, 08/2026)
Events, total population	15 of 130	50 of 127	(Alecensa package insert, 08/2026)
Central nervous system recurrence or death, total population	5 of 130	18 of 127	(EMA assessment report, 2024)
Deaths in the primary analysis	2 of 130	4 of 127	(EMA assessment report, 2024)

Central nervous system

In ALINA, recurrence with brain involvement was seen in 4 patients on alectinib, 3.1 percent, and in 14 on chemotherapy, 11 percent (Alecensa package insert, 08/2026). In the prespecified exploratory analysis, there were 5 events of central nervous system recurrence or death with alectinib and 18 with chemotherapy (EMA assessment report, 2024). These data are exploratory and were not the primary outcome.

Overall survival

Overall survival was not yet mature in the primary analysis, with 2.3 percent of deaths in the total population (Alecensa label of 08/2026). There were 2 deaths in 130 with alectinib and 4 in 127 with chemotherapy, hazard ratio of 0.46 with interval of 0.08 to 2.52 (EMA assessment report, 2024). Minimum follow-up was about 18.5 months and maximum about 58 months (EMA assessment report, 2024). The EMA report notes that the clinical benefit in the adjuvant setting depends on showing a lasting effect, visible as a plateau in the curves (EMA assessment report, 2024). For this reason, the company committed to submitting the updated disease-free survival analysis by the third quarter of 2025 and the final overall survival by the third quarter of 2027 (EMA assessment report, 2024). In the sources read for this text, that overall survival analysis does not yet appear. So what ALINA showed was less recurrence, not proven cure.

Similar studies

First-generation crizotinib did not prolong disease-free survival in operated stage II to III ALK-positive cancer, in the E4512 study (Gerber and colleagues, 2026). Ensartinib, in another phase 3 study against placebo, had 87.3 percent disease-free survival at 24 months versus 57.2 percent with placebo, but overall survival was also immature (Kemper and colleagues, 2024). None of these studies answers whether giving the drug for more than 2 years would reduce recurrences after the end of treatment.

How to use adjuvant alectinib

Dose and duration

The label indicates 600 mg orally twice a day, with food, for 2 years or until recurrence or unacceptable toxicity (Alecensa label of 08/2026). The capsules are 150 mg and must be swallowed whole, without opening or dissolving (Alecensa label of 08/2026). If the patient forgets a dose or vomits after taking it, they should take the next one at the scheduled time (Alecensa label of 08/2026). In severe hepatic impairment, Child-Pugh class C, the dose is 450 mg twice a day (Alecensa label of 08/2026). A review notes that taking 4 capsules twice a day for 2 years can weigh on adherence (Santoni-Rugiu and colleagues, 2025).

Dose reduction

The first reduction is to 450 mg twice a day, and the second to 300 mg twice a day (Alecensa label of 08/2026). Those who do not tolerate 300 mg twice a day should stop the drug (Alecensa label of 08/2026). In ALINA, dose reductions or interruptions were more frequent with alectinib, 36.7 percent, than with chemotherapy, 20.0 percent (EMA assessment report, 2024). Discontinuation due to selected adverse events was more common with chemotherapy, 8.3 percent, than with alectinib, 4.7 percent (EMA assessment report, 2024).

What to monitor

Monitoring starts before the first capsule. The points below come from the label.

• Liver tests every 2 weeks in the first 3 months and then every month, with interruption, reduction or stopping according to severity.
• Creatine phosphokinase every 2 weeks in the first month and when there is unexplained muscle pain, tenderness or weakness.
• Regular heart rate and blood pressure, because the drug can cause bradycardia.
• Immediate interruption if there is interstitial lung disease or pneumonitis, with permanent discontinuation if there is no other cause.
• Triglycerides before starting and during treatment, due to the risk of pancreatitis, and attention to hemolytic anemia.
• Effective contraception, because alectinib can cause fetal harm, and no breastfeeding during use.

The items summarize the label warnings (Alecensa label of 08/2026). In ALINA, muscle events, including increased creatine phosphokinase, were seen in 71.9 percent of the alectinib arm and in 10.0 percent of chemotherapy (EMA assessment report, 2024). The increase, when severe, leads to interruption and then to resuming with the same dose or a lower dose (Alecensa label of 08/2026). The most common reactions, in 20 percent or more, were liver toxicity, constipation, tiredness, muscle pain, edema, skin rash and cough (Alecensa label of 08/2026).

Follow-up

Follow-up combines toxicity monitoring and the search for recurrence. Because ALINA recorded brain recurrences in both arms (Alecensa label from 08/2026), the team must ask about neurological symptoms at every visit. The teacher in the scene needs to know that treatment lowers the risk of the disease coming back but does not eliminate that risk. The post about interprofessional clinical reasoning shows how pharmacy, nursing and medicine share this monitoring.

Regulatory status: FDA and EMA

FDA

Alecensa has NDA 208434 at the FDA (Drugs@FDA, NDA 208434). The original approval was on 12/11/2015, as a new molecular entity, with priority review and orphan drug designation (Drugs@FDA, NDA 208434). The adjuvant indication came with the efficacy supplement approved on 04/18/2024 (Drugs@FDA, NDA 208434) (FDA approval letter from 04/18/2024). An efficacy supplement from 06/11/2026 updated the overall survival data from the ALEX study, which concerns metastatic disease, not the adjuvant setting (Drugs@FDA, NDA 208434). The current label was revised in 08/2026 (Alecensa label from 08/2026).

EMA

At the EMA, Alecensa received a positive opinion on 12/15/2016 and marketing authorization on 02/16/2017 (Alecensa page on the EMA). The extension for adjuvant treatment was assessed in procedure II/0047, with an opinion from the committee for medicinal products for human use on 04/25/2024 (EMA assessment report, 2024). The European indication refers to resected cancer with high risk of recurrence (Alecensa page on the EMA). The update of disease-free survival and final overall survival were set as conditions after authorization (EMA assessment report, 2024).

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by searching for the ICD-10 code. Adjuvant ALK is a good exercise because the most important decision, ordering the test, happens in a visit where the patient appears cured. The post about case-based learning explains why this format fixes knowledge.

Three exercises with cases

Change the size. Say what changes if the tumor were 2.5 cm and no lymph node were involved.

Change the target. Say what changes if the molecular profile showed an EGFR mutation instead of ALK.

Change the liver. Say what you would do if transaminases rose to six times the upper limit in the second month.

The post about simulation of care helps train the conversation about benefit and uncertainty, and the post about clinical deterioration in the ward helps recognize the worsening of a patient undergoing cancer treatment.

Neoadjuvant strategies

Several groups study giving the ALK inhibitor before surgery (Lee and colleagues, 2023) (Kemper and colleagues, 2024). The ALNEO study evaluates alectinib for 8 weeks before surgery and then for up to 96 weeks (Kemper and colleagues, 2024). These data are still from phase 2 and do not change the current indication (Fuorivia and colleagues, 2024). A review on the relationship between targeted therapy and surgery recalls that the decision must be made by the multidisciplinary team from diagnosis (Yin and Antonoff, 2025).

The limits of using the game are described on the NEXO economy page. If you research teaching of clinical reasoning, the page for researchers explains how to get in touch. Professionals who write or review cases find information in curation and in creators, and institutions can learn about the proposal on the for partnerships page.

Frequently asked questions

Does adjuvant alectinib cure ALK-positive lung cancer?

That cannot be said. The study showed fewer recurrences, but overall survival was immature in the primary analysis (Alecensa label from 08/2026) (EMA assessment report, 2024).

Should I order ALK testing for every operated patient?

In candidates for systemic therapy after surgery, testing the resected tumor guides the choice between targeted therapy, chemotherapy and immunotherapy (Jeon et al., 2025) (Nohra et al., 2026).

What is the dose?

600 mg orally twice a day, with food, for 2 years (Alecensa package insert, 08/2026).

Is a patient with a 3 cm tumor and no lymph node involvement a candidate?

According to the FDA label, no. The indication requires a tumor of 4 cm or more or a positive lymph node (Alecensa package insert, 08/2026).

Can the patient become pregnant during treatment?

No. The label recommends effective contraception because the drug can cause fetal harm (Alecensa package insert, 08/2026).

Final checklist

• I ordered ALK testing and the molecular profile on the resected tumor.
• I checked tumor size and lymph nodes in the pathology report of the specimen.
• I explained that the demonstrated benefit is fewer recurrences.
• I prescribed 600 mg twice a day with food for 2 years.
• I scheduled liver and creatine phosphokinase tests.
• I gave guidance on bradycardia, pulmonary symptoms and muscle pain.
• I gave guidance on contraception and breastfeeding.
• I planned follow-up with attention to neurological symptoms.

Want to practice your reasoning with progressive clues? Play the case of the day.

References

1. Chen MF, Chaft JE. Early-stage anaplastic lymphoma kinase (ALK)-positive lung cancer: a narrative review. Transl Lung Cancer Res. 2023. PMID 36895922.
2. European Medicines Agency. Alecensa | European Medicines Agency (EMA). Accessed on 24/10/2026. Official source.
3. European Medicines Agency. Assessment report. Alecensa. Procedure No. EMEA/H/C/004164/II/0047. 25/04/2024. Official source.
4. Food and Drug Administration. Drugs@FDA: FDA-Approved Drugs. NDA 208434, Alecensa. Accessed on 24/10/2026. Official source.
5. Food and Drug Administration. NDA 208434/S-015. SUPPLEMENT APPROVAL. Approval letter of 18/04/2024. Official source.
6. Fuorivia V, Attili I, Corvaja C, et al. Management of Non-Metastatic Non-Small Cell Lung Cancer (NSCLC) with Driver Gene Alterations: An Evolving Scenario. Curr Oncol. 2024. PMID 39330007.
7. Genentech. ALECENSA® (alectinib) capsules, for oral use. Label revised in 08/2026. Official source.
8. Gerber DE, Wang Y, Langer CJ, et al. Crizotinib versus observation or placebo for surgically resected early-stage ALK-positive non-small-cell lung cancer (Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E4512): a phase 3 trial. Lancet Respir Med. 2026. PMID 42641639.
9. Houda I, Dickhoff C, Uyl-de Groot CA, et al. New systemic treatment paradigms in resectable non-small cell lung cancer and variations in patient access across Europe. Lancet Reg Health Eur. 2024. PMID 38476748.
10. Hsu R, Arter ZL, Poei D, et al. A narrative review on perioperative systemic therapy in non-small cell lung cancer. Explor Target Antitumor Ther. 2024. PMID 39280253.
11. Jeon H, Wang S, Song J, et al. Update 2025: Management of Non‑Small-Cell Lung Cancer. Lung. 2025. PMID 40133478.
12. Kemper M, Elges S, Kies P, et al. What do we know about the role of neoadjuvant targeted therapy in early-stage EGFR-mutant and ALK-fused non-small cell lung cancer?-a narrative review of the current literature. Transl Lung Cancer Res. 2024. PMID 39507015.
13. Lavaud P, Bortolot M, Zullo L, et al. Early-Stage Non-Small Cell Lung Cancer: New Challenges with Immune Checkpoint Blockers and Targeted Therapies. Cancers (Basel). 2024. PMID 39199552.
14. Lee JM, McNamee CJ, Toloza E, et al. Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives. J Thorac Oncol. 2023. PMID 37451404.
15. Nohra E, Najdi T, El Karak AS, et al. Multiple Options, One Objective: Clearer Decisions in Resectable Non-Small Cell Lung Cancer. Cancers (Basel). 2026. PMID 42794929.
16. Santoni-Rugiu E, Sørensen JB, Urbanska EM. Alectinib impressively enters the adjuvant setting for early-stage ALK-rearranged non-small cell lung cancer and outperforms chemotherapy-let's define who benefits the most. Transl Lung Cancer Res. 2025. PMID 40114944.
17. Yin V, Antonoff MB. The Evolving Interplay Between Targeted Therapy and Surgery for Resectable Lung Cancer. Cancers (Basel). 2025. PMID 41228366.