Brief Communication
Making Sense of Immunotherapy for Non-Small Cell Lung Cancer (NSCLC)
Medical writer: Stijn van den Borne, MSc | Last updated: 26th March 2018 | In: Guidelines, ImmunoOncology, Immunotherapy, Lung Cancer, Oncology
Rapid development and fast-tracked approvals of immune-checkpoint inhibitors have led to the first registration in non-small cell lung cancer (NSCLC) in 2015. Just over two years later, immunotherapies start to dominate the frontline treatment of NSCLC. This expansion of therapeutic options will soon reflect in dramatic changes to the treatment guidelines, where immunotherapies are expected to complement the chemotherapeutic options. A brief communication of the relevant immuno-oncology data in NSCLC.
Article Keywords
AstraZeneca, atezolizumab, Avastin, AZ, bevacizumab, BMS, Bristol-Myers Squibb, carboplatin, cisplatin, CTLA4, docetaxel, durvalumab, gemcitabine, Genentech, Imfinzi, ipilimumab, Keytruda, Merck, MSD, nivolumab, Opdivo, paclitaxel, PD-1, PD-L1, pembrolizumab, pemetrexed, Roche, Tecentriq, Yervoy
Pembrolizumab immunotherapy in the 1st-line NSCLC
In the open-label Phase II KEYNOTE-021 study, the addition of pembrolizumab to carboplatin and pemetrexed in patients with non-squamous NSCLC (N=123) improved the overall response rate (ORR) to 55% from 29% with the doublet alone (P=0.0032). An improvement regardless of PD-L1 expression. The median progression-free survival (PFS) was 13.0 months with the addition of pembrolizumab vs 8.9 months for the pemetrexed/carboplatin doublet (HR=0.53, P=0.0205, 95% CI, 0.31-0.91). Patients in the pembrolizumab arm continued to receive the immunotherapy up to 24 months. After a median 10.6 months follow-up, 88% of patients in the experimental-arm remained alive and progression-free compared to 78% of patients receiving the doublet.
The multi-centre, double-blind, Phase III KEYNOTE-189 trial confirmed the early results of the KEYNOTE-021 study. In the KEYNOTE-189 study, 616 EGFR– or ALK-negative non-squamous NSCLC patients were randomised 2:1 to receive frontline pembrolizumab or placebo in combination with pemetrexed and a platinum salt. The co-primary endpoints of improved overall survival (OS) and PFS were met and published in the New England Journal of Medicine in April 2018.
Single-agent pembrolizumab
At a median follow-up of 25.2 months in the open-label KEYNOTE-024 study, pembrolizumab more than doubled median OS compared to platinum-based chemotherapy in 154 NSCLC patients with a PD-L1 expression ≥50% and negative EGFR- or ALK-status. Single-agent pembrolizumab led to a 30.2 months OS vs 14.2 months with chemotherapy (HR=0.63, P=0.002; 95% CI, 0.47-0.86) despite the crossover of 82 patients from the chemotherapy-arm to the pembrolizumab-arm. The 24-month OS-rate favoured pembrolizumab vs platinum doublet: 51.5% vs 34.5% respectively and the ORR was 45.5% in the pembrolizumab-arm compared to 29.8% in the chemotherapy-arm.
Durvalumab for maintenance after frontline chemoradiotherapy in NSCLC
The phase III PACIFIC trial (N=709) randomised patients 2:1 to either receive durvalumab or placebo after chemoradiotherapy. Durvalumab-maintenance therapy was associated with improved median PFS, 16.8 months in the durvalumab-group vs 5.6 months in the placebo group (HR=0.52, P<0.0001; 95% CI, 0.42-0.65). The 12-month and 18-month PFS-rates both favoured the immunotherapy: 55.9% (durvalumab) vs 35.3% (placebo) and 44.2% (durvalumab) vs 27.0% (placebo) respectively, and was irrespective of PD-L1 expression before chemoradiotherapy. Durvalumab treatment was associated with a higher ORR of 28.4% vs 16.0% with placebo. Patients with a response to the immune-checkpoint inhibitor had durable, ongoing responses of 72.8% at both 12 and 18 months. In the placebo-arm, the 12- and 18-month ORRs were 56.1% and 46.8%, respectively.
Newsletter Sign-Up
Do you like our content? Subscribe to our non-intrusive newsletter today! We promise we won’t be spammy.
YOU MAY ALSO LIKE
Nivolumab plus ipilimumab immunotherapy in front-line NSCLC
Preliminary results of the Phase III CheckMate 227 show that the combination of nivolumab and ipilimumab improves PFS when compared with chemotherapy in treatment-naïve patients with high mutation burden (high-TMB) NSCLC. The co-primary PFS endpoints was met and published in the New England Journal of Medicine in April 2018.
Common nivolumab and ipilimumab-related side effects.
Atezolizumab immunotherapy in the 1st-line treatment of NSCLC
In the multicenter, open-label Phase II IMpower131, the addition of atezolizumab to 4 or 6 cycles of carboplatin and nab-paclitaxel in the 1st-line delayed progression or death compared with chemotherapy alone in patients with advanced squamous non–small cell lung cancer (NSCLC). The co-primary endpoints were PFS and overall survival OS and the latter was not improved. The results have not yet been published.
The Phase III IMpower150 trial previously showed that the addition of atezolizumab to bevacizumab, carboplatin, and paclitaxel delayed progression or death by 38% in patients with advanced non-squamous NSCLC. The median PFS improved to 8.3 months compared with 6.8 months for bevacizumab and chemotherapy alone (HR=0.62, P<0.0001; 95% CI=0.52-0.74). The 12-month PFS-rate was 37% after addition of atezolizumab vs 18% for bevacizumab plus chemotherapy alone. The preliminary OS improved to 19.2 months vs 14.4 months respectively (HR=0.775, P=0.0262; 95% CI=0.619-0.970).
REFERENCES
1. Prescribing information pembrolizumab (Keytruda®), revised: 11/2017
2. Langer, CJ et al. Lancet Oncol 2016;17(11):1497-1508
3. Merck Press Release KEYNOTE-189, accessed 26 March 2018
4. Prescribing information durvalumab (Imfinzi®), revised: 02/2018
5. Antonia SJ et al. N Engl J Med. 2017;377(20):1919-29
6. BMS Press Release CheckMate-227, accessed 26 March 2018
7. Prescribing information nivolumab (Opdivo®), revised: 02/2018
8. Roche Press Release IMpower-131, accessed 26 March 2018
9. Reck M et al. Ann Oncol 2017;28(S11):xi31
10. Prescribing information atezolizumab (Tecentriq®), revised: 04/2017
Disclaimer
This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).
© Copyright 2018 MediPaper Medical Communications Ltd. – Making sense of immunotherapy for non-small cell lung cancer (NSCLC)
YOU MAY ALSO LIKE
© Copyright 2018 MediPaper Medical Communications Ltd. – Making sense of immunotherapy for non-small cell lung cancer (NSCLC)
Trackbacks & Pingbacks
[…] non-small cell lung cancer (NSCLC) with PD-L1 TPS (tumour proportion score) ≥1% […]
[…] programmed death 1 (PD-1)–axis have demonstrated significant overall survival (OS) benefit in the 2nd-line treatment for advanced NSCLC. Tumour- and immune-cell PD-1 ligand (PD-L1) expression has shown to partially predict the clinical […]
[…] Non-small cell lung cancer (NSCLC) is a key feature of the American Society of Clinical Oncology (ASCO) 2018 annual meeting. This year, encouraging results with combinations therapies were presented, including CheckMate 227 with nivolumab (NIVO), IMpower131 and IMpower150 studies with atezolizumab (ATEZO), and KEYNOTE-042 and KEYNOTE-407 studies with pembrolizumab (PEMBRO). Important Asian data on treatments for epidermal growth-factor recptor (EGFR) mutation-positive (mu+) NSCLC (ARCHER 1050, NEJ009, NEJ026, and JO25567) were also featured. Welcome to the summary of the ASCO 2018 NSCLC track. […]
[…] non-small cell lung cancer (NSCLC) with PD-L1 TPS (tumour proportion score) ≥1% […]
[…] with advanced non-squamous non-small cell lung cancer (NSCLC) treated with first-line atezolizumab (Tecentriq®) plus bevacizumab (Avastin®), carboplatin, and […]
Leave a Reply
Want to join the discussion?Feel free to contribute!