Patient Education

Amongst the many investigations and updates discussed at the American Society of Oncology (ASCO) Annual Meeting this year, results of some have broadened treatment options and strategies in the management of lung cancer.

Any patient who has been diagnosed with advanced Non-Small Cell Lung Cancer (NSCLC) should have their tumour tissue undergo comprehensive genetic testing to help formulate the best treatment plan for that particular cancer. The known genes altered in NSCLC include EGFR, ALK, ROS1, BRAF, MET, HER2, RET, and NTRK1. Of them, EGFR, ALK, ROS1, and BRAF can be targeted with approved treatments. The other genetic changes can be successfully targeted with investigational agents that are being tested in clinical trials. Newer tests also look at programmed cell death ligand 1 (PD-L1) expression as well as Tumour Mutational Burden (TMB) to predict whether a tumour is likely to respond to immunotherapy.

A study presented at ASCO 2018 demonstrated the economic benefit of using upfront comprehensive next-generation sequencing in patients diagnosed with advanced NSCLC as compared to single tests done sequentially (1). This has also been our approach over the past year or so.

A lot of new information regarding immunotherapy in Lung Cancer- Dr Lopes presented data from the KEYNOTE-042 trial that essentially showed that treatment with immunotherapy using Pembrolizumab (Keytruda) led to patients’ living longer on average as compared to those treated with standard chemotherapy. Median overall survival was improved by 4 to 8 months in patients enrolled in the trial, all of whom had tumours with programmed cell death ligand 1 (PD-L1) expression of 1% or more. Moreover, immunotherapy with pembrolizumab was associated with fewer severe side effects than chemotherapy (17.8% vs 41%, respectively). (2)This study essentially reinforces the use of immunotherapy in advanced lung cancer in almost all patients without driver mutations. The IMpower150 trial also showed benefit from another immunotherapy drug, Atezolizumab (Tecentriq)  in first line treatment of advanced NSCLC when combined with Chemotherapy and Avastin irrespective of PDL-1 status(3). A non-chemotherapy option of two immunotherapy drugs combined together- Nivolumab and Ipilimumab were tested in Checkmate 227 trial. This trial demonstrated superiority of the immunotherapy combination over chemotherapy in patients with high TMB.(4) The KEYNOTE-407, a study exploring the addition of Keytruda (Pembrolizumab – a PD1 inhibitor) to standard chemotherapy was discussed (5).  This study enrolled patients diagnosed with advanced squamous cell lung cancer, randomly assigning them to treatment with standard chemotherapy or chemotherapy plus immunotherapy.  The results showed that combined treatment led to improvement in survival when compared with chemotherapy alone.  This mirrored results of a similar study in patients who had non-squamous cell lung cancer. The IMpower131 also showed a benefit of addition of Atezolizumab to chemotherapy in a squamous non-small cell lung cancer, but survival data is not yet mature. (6)

Immunotherapy also seems to have an emerging role in Small Cell Lung Cancer and Malignant Mesothelioma. More trial data is awaited.

Mutation driven lung cancers- The NEJ026 study from Japan demonstrated the benefit of adding Avastin to Erlotinib over Erlotinib alone in patients with advanced NSCLC with EGFR mutation. The combination controlled the tumour by an average of 3 months more over Erlotinib alone (7).

Another interesting study from Japan, patients with a sensitizing Epidermal Growth Factor Receptor (EGFR) mutation in their tumours are managed differently, the NEJ009 trial evaluated the benefit of adding chemotherapy to Gefitinib in patients with advanced EGFR mutant lung cancers (8). Standard treatment for such patients involves the use of one of the oral targeted medication inhibiting the action of the EGFR.  A study conducted in Japan and discussed at the oral presentation showed that the addition of chemotherapy to Gefitinib (an EGFR targeting drug) in patients with advanced lung cancer harbouring a sensitive EGFR mutation resulted in higher likelihood of response and better survival when compared with treatment using the targeted treatment alone. However, now with availability of third generation tyrosine kinase inhibitor (TKI) Osimertinib, it is unclear how this new information will change clinical practice. A couple of small trials suggest that immunotherapy should not be combined with ALK-inhibitors in ALK positive lung cancer due to lack of benefit and increased toxicity.

Lung cancer patients should be aware of these studies and its recent advances which may potentially be helpful when planning their treatment.

“Expert knowledge means better care for cancer”

References

1. Pennell NA, Mutebi A, Zhou Z, et al: Economic impact of next generation sequencing vs sequential single-gene testing modalities to detect genomic alterations in metastatic non-small cell lung cancer using a decision analytic model. 2018 ASCO Annual Meeting. Abstract 9031. Presented June 3, 2018.
2. Lopes G, Wu Y-L, Kudaba I, et al: Pembrolizumab versus platinum-based chemotherapy as first-lone therapy for advanced metastatic NSCLC with a PD-L1 tumor proportion score ≥ 1%: Open-label, phase 3 KEYNOTE-042 study. 2018 ASCO Annual Meeting. Abstract LBA4. Presented June 3, 2018.
3. Socinski M et al. Overall Survival (OS) analysis of IMpower150, a randomized Ph 3 study of atezolizumab (atezo) + chemotherapy (chemo) ± bevacizumab (bev) vs chemo + bev in 1L non squamous (NSQ) NSCLC. Abstract #9002
4. Borghaei H, Hellmann MD, Paz-Ares LG, et al. Nivolumab (Nivo) + platinum-doublet chemotherapy (Chemo) vs chemo as first-line (1L) treatment (Tx) for advanced non-small cell lung cancer (NSCLC) with <1% tumor PD-L1 expression: Results from CheckMate 227. J Clin Oncol. 2018;36 (suppl; abstr 9001).
5. Paz-Ares LG, Luft A, Tafreshi A, et al. Phase 3 study of carboplatin-paclitaxel/nab-paclitaxel (Chemo) with or without pembrolizumab (Pembro) for patients (Pts) with metastatic squamous (Sq) non-small cell lung cancer (NSCLC). J Clin Oncol. 2018;36 (suppl; abstr 105).
6. Jotte RM, Cappuzzo F, Vynnychenko I, et al. IMpower131: Primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. J Clin Oncol. 2018;36 (suppl; abstr LBA9000).
7. J Clin Oncol 36, 2018 (suppl; abstr 9006)
8. J Clin Oncol 36, 2018 (suppl; abstr 9005)