Therapeutic Advances in Lung Cancer – 2nd Trimester 2022

Therapeutic Advances in Lung Cancer – 2^nd Trimester 2022

Modern thoracic oncology is a highly dynamic field with continuous introduction of new therapies that improve patient survival. Aim of this series is to summarize recent developments of immediate practical interest.

1. Approval of Atezolizumab as adjuvant immunotherapy for non-small-cell lung cancer with high PD-L1 expression

On June 9^th, 2022, the PD-L1 inhibitor atezolizumab  was approved by the European Medicines Agency (EMA) as adjuvant therapy after complete surgical resection and platinum-based chemotherapy for stage ΙΙ-ΙΙΙΑ non-small-cell lung cancer (NSCLC) with PD-L1 expression on ≥ 50% of tumor cells and wild-type EGFR/ALK. The drug is administered intravenously every 3 weeks for one year and reduced the risk of cancer recurrence or death by 57% in the phase 3 IMpower010 trial (3-year relapse-free survival 75% with atezolizumab vs. 50% without). This is a major milestone and represents the first approval of immunotherapy for patients with operable lung cancer in Europe. A significant survival benefit was recently announced for postoperative administration of the PD-1 inhibitor pembrolizumab , as well, in the phase 3 trial Keynote-091, but approval is still pending. Besides, preoperative immunotherapy is also emerging as an alternative option for these patients: as announced at the American Association for Cancer Research (AACR) conference on April 10^th, three cycles of the PD-1 inhibitor nivolumab administered preoperatively together with platinum-based chemotherapy reduced the risk of NSCLC recurrence or death after surgical resection by 37% in the phase 3 study Checkmate-816 (2-year relapse-free survival 64% vs. 45% with preoperative chemotherapy alone; for certain subsets, e.g. tumours with high PD-L1 expression, the benefit was even greater). Preoperative chemoimmunotherapy for NSCLC is already routinely available in the USA, while approval by the EMA is expected during the next months.

Ref:

• https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02098-5/fulltext
• https://www.annalsofoncology.org/article/S0923-7534(22)00340-4/fulltext
• https://aacrjournals.org/cancerres/article/81/13_Supplement/CT003/669724/Abstract–CT003-Nivolumab–NIVO–platinum–doublet

2. Approval of Selpercatinib as first-line treatment for non-small-cell lung cancer with RET fusion

On June 21^st, 2022, the European Medicines Agency (EMA) extended approval of the tyrosine kinase inhibitor selpercatinib  as first-line treatment of advanced NSCLC with a RET fusion (detectable in approximately 1-2% of cases). This decision was based on the latest data from the phase II clinical study LIBRETTO-001, which were presented at the European Lung Cancer Conference (ELCC) on April 3^rd, 2022 and complements a previous approval of the same drug on February 12^th, 2021 after failure of platinum-based chemotherapy or immunotherapy. Selpercatinib is administered orally once daily, generally well-tolerated, and much more active than chemotherapy, causing significant tumor shrinkage (partial remission) in 84% of patients with a median duration of response approaching two years. A second selective RET inhibitor, pralsetinib , is also approved as first-line treatment for the same patients since December 9^th, 2021.

Ref:

• https://www.annalsofoncology.org/article/S0923-7534(22)00152-1/fulltext
• https://www.nejm.org/doi/full/10.1056/NEJMoa2005653

3. Approval of Capmatinib as second-line treatment for non-small-cell lung cancer with MET exon 14 skipping.

On June 22^nd, 2022 the tyrosine kinase inhibitor capmatinib  was approved by the European Medicines Agency (EMA) as second -line treatment for patients with metastatic NSCLC harboring MET exon 14 skipping (METΔex14, detectable in approximately 2-3% of cases). It is administered orally twice daily regardless of meals and caused tumour shrinkage in most (52%) patients, as observed in the phase II Geometry-mono-1 study. Tolerability is generally good, with peripheral edema as the main side effect. Capmatinib is the second targeted drug to enter the therapeutic armamenterium for patients with METΔex14-mutated lung cancer, following the recent approval of tepotinib in February 2022 also for second-line use, while further MET inhibitors are in advanced clinical testing.

Ref:

• https://www.nejm.org/doi/full/10.1056/nejmoa2002787
• https://www.annalsofoncology.org/article/S0923-7534(22)00151-X/fulltext

We thank Dr. Petros Christopoulos for granting this interview to FairLife L.C.C.