Complete pathologic response to short-course neoadjuvant alectinib in mediastinal node positive (N2) ALK rearranged lung cancer.

OBJECTIVES

Neoadjuvant therapy prior to surgical resection for locally advanced lung cancer has evolved to incorporate systemic cytotoxic chemotherapy +/- immunotherapy +/- radiotherapy. The role of neoadjuvant precision therapies remains understudied.

MATERIALS AND METHODS

We report cases with major and complete pathologic responses to off-label neoadjuvant alectinib.

RESULTS

A case with stage IIIA (cT1b cN2 cM0) EML4-ALK variant 3a/b lung adenocarcinoma received 6 weeks of alectinib followed by R0 left upper lobectomy with complete pathological response (ypT0 ypN0). Another case with stage IIIA (cT3 cN2 cM0) EML4-ALK variant 2 received 12 weeks of alectinib followed by R0 right middle lobectomy with a major pathologic response (ypT1a ypN0) but systemic recurrence 12 months post-operatively.

CONCLUSION

Ongoing clinical trials are evaluating the role of both neoadjuvant and adjuvant ALK-directed therapy. Our cases support the completion of ongoing trials (ALINA: NCT03456076 and ALNEO: NCT05015010), and highlight the ability of second generation ALK inhibitors to induce major and complete pathologic responses in the neoadjuvant setting plus the likely role of long-term adjuvant kinase inhibitor therapy to prevent radiographic/clinical recurrence.