Alecensa (alectinib) Offers Hope for Certain Patients With ALK Positive NSCLC

December 10, 2024
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When Matt was diagnosed with ALK-positive (ALK+) metastatic non-small cell lung cancer (mNSCLC), his world turned upside down. It’s a moment that many patients like Matt dread — the words “you have cancer” hang in the air, bringing with it waves of fear and uncertainty. For Matt, a Stage 4 diagnosis meant facing an uncertain future. His wife, a nurse, grasped the severity more than he did, while Matt was still coming to terms with what his diagnosis meant.

“I didn’t know what to expect,” Matt recalls. “My wife understood it better than I did, but for me, it was like, ‘Okay, I have cancer — what now?'”

The “what now” led Matt to Alecensa® (alectinib), a treatment that has helped to redefine what it means to live with an ALK+ mNSCLC diagnosis. Alecensa has been available as a treatment option for patients like Matt since it was first approved in 2015 for metastatic ALK+ NSCLC. It was later extended to some earlier stages of the disease, when it was approved in 2024 for treatment after surgery, or adjuvant therapy.1

A New Normal for Matt

When Matt started Alecensa, his mindset began to shift. “Even though I’m a Stage 4 cancer patient, I don’t feel like one,” Matt notes. “I take the Alecensa pills in the morning and at night. It has become part of my new normal.”

For Matt, Alecensa wasn’t just a cancer treatment; making the informed decision to start Alecensa with his physician gave him a sense of control in a situation that often feels uncontrollable. “Starting treatment brought a new sense of hope,” he shares, reflecting on the positive changes he felt soon after beginning Alecensa.

Alecensa has proven its superiority over another ALK inhibitor in extending progression-free survival. In the Phase III ALEX study, Alecensa significantly reduced the risk of disease worsening or death by 47% (HR=0.53, 95% CI: 0.38, 0.73, p<0.0001) compared to crizotinib as assessed by independent review committee (IRC). In fact, Alecensa is prescribed more than any other 1L treatment for ALK+ mNSCLC.1,2,†

Alecensa not only has the ability to delay disease progression, but it also helps manage central nervous system (CNS) metastases, which can often be challenging for patients. In the ALEX trial, Alecensa reduced the risk of tumors spreading to or growing in the CNS as the first site of progression by 84% compared to crizotinib (HR=0.16, 95% CI: 0.10-0.28, p<0.0001), regardless of whether patients had CNS metastases at baseline. The most common adverse reactions (≥20%) in patients who have received ALECENSA as a single agent include hepatotoxicity (41%), constipation (39%), fatigue (36%), myalgia (31%), edema (29%), rash (23%), and cough (21%).1,3

Alecensa’s Expanding Role in an Ever-Evolving Landscape

Matt’s story, while deeply personal, is part of a much larger narrative. Alecensa’s April 2024 approval for certain early-stage ALK+ NSCLC after tumor resection marks an important milestone in cancer care. The ALINA study, which formed the basis for this approval, showed that Alecensa reduced the risk of cancer recurrence by 76% (HR=0.24, 95% CI: 0.13-0.43, p<0.0001) in early-stage patients with Stage IB (tumors ≥ 4 cm) – IIIA (UICC/AJCC) 7th edition — a finding that supports Alecensa’s role across multiple stages of the disease.1

For healthcare providers like Dr. Nicholas Rohs, an oncologist at the Icahn School of Medicine at Mount Sinai, Alecensa represents more than just a treatment option; it is an important part of a comprehensive approach to managing an increasingly complex cancer landscape. “Every patient comes with different barriers and stumbling blocks,” Dr. Rohs says. “We have a great social work team that partners with us, making sure each patient gets the cultural and emotional support they need. It’s multidisciplinary care at its best.”

A Legacy Built to Last

The story of Alecensa, and patients like Matt, is one of perseverance and hope. Despite the many challenges that come with an ALK+ mNSCLC diagnosis, Alecensa has demonstrated strong pivotal results that are also supported by longer-term data. An exploratory overall survival (OS) analysis from the ALEX study showed that 60% of patients on Alecensa were still alive at the five-year mark, a remarkable statistic in a field where survival rates are often measured in months, not years, compared to 48% of patients who received crizotinib.3,4 At the time of primary cutoff the OS data were not mature and the median OS had not been reached. This post-hoc OS analysis, conducted at ~5 years after randomization of the last patient was not powered to show statistical significance.

“When I realized I’d be on Alecensa, it was a reminder that this is a treatable condition,” Matt reflects. “I’ve made it to the two-year mark with no evidence of disease progression.”

Alecensa remains the standard of care in ALK+ NSCLC.†,2 “With the treatment landscape constantly evolving, biomarker testing is critical to identify the appropriate patients for whom targeted treatment may help them achieve better outcomes,” says Dr. Rohs. “In an ideal world, every one of my patients would undergo this testing. A collaborative, multidisciplinary approach also helps us manage this complexity, ensuring each patient receives the most comprehensive care possible.”

For patients like Matt, and the doctors who guide them through their cancer journey, Alecensa may offer more than just a treatment option — it may offer a path forward, more control over one’s treatment plan, and most importantly, hope.

†According to IQVIA Claims from December 2022–March 2024, which included 1L ALK+ mNSCLC patients identified through their first use of an ALK product.

Indications

ALECENSA is a kinase inhibitor indicated for:

  • adjuvant treatment in adult patients following tumor resection of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) (tumors ≥4 cm or node positive), as detected by an FDA-approved test
  • treatment of adult patients with ALK-positive metastatic NSCLC as detected by an FDA-approved test

Important Safety Information

Warnings and Precautions

Hepatotoxicity

  • Severe hepatotoxicity, including drug-induced liver injury, occurred in patients treated with ALECENSA. Hepatotoxicity occurred in 41% of 533 patients treated with ALECENSA and the incidence of Grade ≥3 hepatotoxicity was 8%. In the ALINA study, hepatotoxicity occurred in 61% of patients treated with ALECENSA and the incidence of Grade ≥3 hepatotoxicity was 4.7%. The majority (72% of 136 patients) of elevated transaminases occurred during the first 3 months of treatment. Treatment discontinuation due to hepatotoxicity occurred in 3.6% of patients who received ALECENSA in the pooled safety population and 1.6% of patients treated in the ALINA study
  • Concurrent elevations in alanine transaminase (ALT) or aspartate transaminase (AST) greater than or equal to 3 times the ULN and total bilirubin greater than or equal to 2 times the ULN, with normal alkaline phosphatase, occurred in less than 1% of patients treated with ALECENSA. Three patients with Grades 3-4 AST/ALT elevations had drug-induced liver injury (documented by liver biopsy in 2 cases)
  • Monitor liver function tests including ALT, AST, and total bilirubin every 2 weeks during the first 3 months of treatment, then once a month and as clinically indicated, with more frequent testing in patients who develop transaminase and bilirubin elevations. Based on the severity of the adverse drug reaction, withhold ALECENSA and resume at a reduced dose, or permanently discontinue ALECENSA

Interstitial Lung Disease (ILD)/Pneumonitis

  • ILD/pneumonitis occurred in 1.3% of 533 patients treated with ALECENSA with 0.4% of patients experiencing Grade 3 ILD/pneumonitis. Five patients (0.9%) discontinued ALECENSA due to ILD/pneumonitis. The median time-to-onset of Grade 3 or higher ILD/pneumonitis was 2.1 months (range: 0.6 months to 3.6 months)
  • Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, and fever)
  • Immediately withhold ALECENSA treatment in patients diagnosed with ILD/pneumonitis and permanently discontinue ALECENSA if no other potential causes of ILD/pneumonitis have been identified

Renal Impairment

  • Renal impairment occurred in 12% of 533 patients treated with ALECENSA, including Grade ≥3 in 1.7% of patients, of which 0.4% were fatal events
  • The median time to Grade ≥3 renal impairment was 3.7 months (range 0.5 to 31.8 months). Dosage modifications for renal impairment were required in 2.4% of patients
  • Permanently discontinue ALECENSA for Grade 4 renal toxicity. Withhold ALECENSA for Grade 3 renal toxicity until recovery to less than or equal to 1.5 times ULN, then resume at reduced dose

Bradycardia

  • Symptomatic bradycardia occurred in patients treated with ALECENSA. Bradycardia occurred in 11% of 533 patients treated with ALECENSA. Twenty percent of 521 patients for whom serial electrocardiograms (ECGs) were available had post-dose heart rates of less than 50 beats per minute (bpm)
  • Monitor heart rate and blood pressure regularly. For asymptomatic bradycardia, dose modification is not required. For symptomatic bradycardia that is not life-threatening, withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm and evaluate concomitant medications known to cause bradycardia, as well as anti-hypertensive medications. If bradycardia is attributable to a concomitant medication, resume ALECENSA at a reduced dose upon recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm, with frequent monitoring as clinically indicated
  • Permanently discontinue ALECENSA in cases of life-threatening bradycardia if no contributing concomitant medication is identified or for recurrence of life-threatening bradycardia

Severe Myalgia and Creatine Phosphokinase (CPK) Elevation

  • Severe myalgia and creatine phosphokinase (CPK) elevation occurred in patients treated with ALECENSA. Myalgia (including muscle- and musculoskeletal-related reactions) occurred in 31% of 533 patients treated with ALECENSA, including Grade ≥3 in 0.8% of patients. Dosage modifications for myalgia events were required in 2.1% of patients
  • Of the 491 with CPK laboratory data available, elevated CPK occurred in 56% of patients, including 6% Grade ≥3. The median time to Grade ≥3 CPK elevation was 15 days (interquartile range 15-337 days). Dosage modifications for elevation of CPK occurred in 5% of patients. In the ALINA study, elevated CPK occurred in 77% of 128 patients with CPK laboratory data, including 6% Grade ≥3 elevations
  • Advise patients to report any unexplained muscle pain, tenderness, or weakness. Assess CPK levels every 2 weeks for the first month of treatment and as clinically indicated in patients reporting symptoms. Based on the severity of the CPK elevation, withhold ALECENSA, then resume or reduce dose

Hemolytic Anemia

  • Hemolytic anemia occurred in patients treated with ALECENSA. Hemolytic anemia was initially reported with ALECENSA in the postmarketing setting, including cases associated with a negative direct antiglobulin test (DAT) result. Assessments for the determination of hemolytic anemia were subsequently collected in the ALINA study, where hemolytic anemia was observed in 3.1% of patients treated with ALECENSA
  • If hemolytic anemia is suspected, withhold ALECENSA and initiate appropriate laboratory testing. If hemolytic anemia is confirmed, consider resuming at a reduced dose upon resolution or permanently discontinue ALECENSA

Embryo-Fetal Toxicity

  • ALECENSA can cause fetal harm when administered to pregnant women. Administration of alectinib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicity and abortion at maternally toxic doses with exposures approximately 2.7-fold those observed in humans with alectinib 600 mg twice daily. Advise pregnant women of the potential risk to a fetus
  • Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for 5 weeks following the last dose
  • Advise males with female partners of reproductive potential to use effective contraception during treatment with ALECENSA and for 3 months following the last dose

Most Common Adverse Reactions

  • The most common adverse reactions (≥20%) were hepatotoxicity (41%), constipation (39%), fatigue (36%), myalgia (31%), edema (29%), rash (23%), and cough (21%)

Use in Specific Populations

Lactation

  • Because of the potential for serious adverse reactions in breastfed infants from ALECENSA, advise a lactating woman not to breastfeed during treatment with ALECENSA and for 1 week after the last dose

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see additional Important Safety Information in full Prescribing Information.

References:

  1. ALECENSA [prescribing information]. South San Francisco, CA: Genentech USA, Inc. 2024.
  2. IQVIA US Claims, December 2022–March 2024.
  3. Data on file. Genentech, Inc.
  4. Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056-1064.

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