Info

🌱 來自: ALK

ALK ASCO recommendation

Clinical Question 3 (from parent guideline) What is the most effective therapy for patients with ALK rearrangement and previously untreated NSCLC?

Recommendation 3.1

For patients with an ALK rearrangement, a PS of 0-2, and previously untreated NSCLC, clinicians should offer alectinib or brigatinib (Type: Evidence based; benefits outweigh harms; Evidence quality: High; Strength of recommendation: Strong) or lorlatinib (Type: Evidence based; benefits outweigh harms; Evidence quality: Low; Strength of recommendation: Weak).

Recommendation 3.2

For patients with an ALK rearrangement, a PS of 0-2, and previously untreated NSCLC, if alectinib, brigatinib, or lorlatinib are not available, clinicians should offer ceritinib or crizotinib (Type: Evidence based; benefits outweigh harms; Evidence quality: High; Strength of recommendation: Strong).

Literature review update and analysis

• The CROWN trial included 296 patients who received either lorlatinib or crizotinib4 (crizotinib data were reviewed in prior guideline updates).
• A difference in OS was not observed, but the survival data were immature at the time of the analysis.
• There was an improvement in PFS compared with crizotinib.
• The PFS difference result was hazard ratio = 0.28 (95% CI, 0.19 to 0.41).
• There was an increase in grade 3-4 AEs with lorlatinib, with an absolute increase of 167 more per 1,000.
• With the GRADE assessment, certainty of the evidence was low for OS and grade 3-4 AEs, and moderate for PFS.

Clinical interpretation

• Although lorlatinib is effective in patients with ALK-rearranged stage IV NSCLC and may be considered as another option for first-line treatment in this patient population, clinicians need awareness of its AE profile.
• Notably, neurocognitive and mood disorders (both any grade), grade 3-4 hypercholesterolemia, and hypertriglyceridemia were increased.
• Weight gain and hypertension were also increased in the lorlatinib arm.
• Because of immature OS results, a wide CI for PFS, methodologic risk of bias, and toxicity, the strength of the recommendation is weak.
• Although no head-to-head comparison of alectinib and lorlatinib has occurred, longer follow-up data with alectinib and its more favorable safety profile still make it the preferred first-line treatment for patients with ALK-rearranged stage IV NSCLC.
• Brigatinib was discussed in the previous version of the guideline; there was no new evidence to add in this update.