Defining an algorithm of best practice for the treatment of lung cancer is an ever-changing endeavour as immunotherapy continues to reveal positive results.
“Immunotherapy is the answer to making further progress in lung cancer,” says Dr. Stefan Zimmermann. “It has found its place in second line and is rapidly affirming its role in first line, alone in some patient subsets, or combination strategies.”
With activating mutations in metastatic lung being twice as high in Asia compared to Europe , there is a need for different treatment algorithms. Unfortunately, huge discrepancies still exist within Asia as well as in Europe in the proportion of patients tested for molecular alterations. “This is acutely problematic in Asia where the frequency of actionable alterations is high and patients would benefit from a given therapy if they were identified,” says Zimmermann.
“But before novel drugs are approved in China or Japan, new clinical trials are needed which seriously delays introduction to the market,” Professor Yi-Long Wu adds.
A hot topic at the first ESMO-ASIA congress is the combination of two families of checkpoint inhibitors, the CTLA-4 inhibitors and PD-1 / PD-L1 inhibitors. The combination seems to provide a clear benefit in efficacy especially in PD-L1 negative patients despite a higher reported rate of toxicity (418O).
Results from CheckMate 057 study confirm the overall survival benefit of nivolumab without compromising quality of life (417O). Health status including mobility, pain and discomfort nearly reaches levels of healthy individuals. Zimmermann says: “Patients with lung cancer have now the prospect of a normal quality of life.” Wu adds: “If CheckMate 078 can repeat these results in Chinese patients it will change clinical practice.”
Meanwhile, results from Phase 2/3 KEYNOTE-010 trial will reveal the results of pembrolizumab, a PD-1 inhibitor, versus docetaxel after platinum-based therapy (LBA3). “If this trial is positive, it is expected to further establish anti-PD-1 inhibition as a standard of care rather than chemotherapy in pretreated patients,” says Zimmermann.
Immunotherapy is not the only promising option on the horizon of lung cancer. Targeted therapies show exciting findings in ALK-rearranged non-small cell lung cancer patients, in whom there is an unmet need for controlling the development of brain metastases (4190). ASCEND-2 and ASCEND-3 showed a 45% overall brain response rate and an 80% intracranial disease control rate with ceritinib as second-line therapy in patients with lung cancer and active brain metastases, similar to results seen with the approved ALK inhibitor alectinib. Zimmermann says: “We now have two second generation ALK inhibitors with similar and impressive efficacy in treating this brain disease.”
Further results suggest that EGFR deletion 19 and L858R mutations are distinctive diseases requiring different treatment strategies (445P, 446P). “Patients aged >65 years and all race subgroups with exon 19 deletion, but not L858R mutations, had overall survival benefit with afatinib compared to chemotherapy,” says Wu.
Eagerly awaited results from the global, randomized, open-label, Phase IIb trial LUX-Lung 7 (LL7) will show the first head to head comparison of first and second generation EGFR inhibitors (LBA2). Wu says: “This trial may give us an answer on which EGFR TKI to choose.”
ESMO Asia 2015 Sessions
Proffered Paper session: Thoracic cancers, 19 December, 14:30 to 16:00, Hall 405
417O Phase 3, randomized trial (CheckMate 057) of nivolumab vs docetaxel in advanced non-squamous (non-SQ) non-small cell lung cancer (NSCLC): Subgroup analyses and patient reported outcomes (PROs)
419O Efficacy and safety of ceritinib in patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) and baseline brain metastases (BM) – results from ASCEND-2 and ASCEND-3
Presidential Symposium, 20 December, 16:30 to 18:00, Hall 406
LBA2 Afatinib (A) vs gefitinib (G) as first-line treatment for patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations: results of the global, randomized, open-label, Phase IIb trial LUX-Lung 7 (LL7)
LBA3 KEYNOTE-010: Phase 2/3 Study of Pembrolizumab (MK-3475) vs Docetaxel for PD-L1–Positive NSCLC After Platinum-Based Therapy