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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Lung cancers that carry a lot of PD-L1 and no targetable mutation can be treated with an immunotherapy antibody alone instead of chemotherapy. Pembrolizumab keeps about a third of patients alive at five years, roughly double what chemotherapy achieved, and adding chemotherapy is reserved for those who need a fast response.
PD-L1 on tumour cells switches off the T cells that would attack them, and the level of expression, measured by immunohistochemistry as the tumour proportion score, was the first biomarker for checkpoint inhibitors in lung cancer. KEYNOTE-024 (2016) randomised 305 patients with untreated advanced non-small-cell lung cancer, PD-L1 of 50 percent or more and no EGFR or ALK alteration to pembrolizumab or platinum chemotherapy: progression-free survival was 10.3 versus 6.0 months, median overall survival 26.3 versus 13.4 months, and 31.9 percent of pembrolizumab patients were alive at five years against 16.3 percent, despite most of the chemotherapy arm crossing over. The FDA approved first-line pembrolizumab monotherapy in October 2016, the first time a checkpoint inhibitor replaced chemotherapy first line in a common cancer.
KEYNOTE-042 (2019) extended monotherapy to PD-L1 of 1 percent or more but showed the gain came from the high expressers; IMpower110 (atezolizumab, 2020) and EMPOWER-Lung 1 (cemiplimab, 2021) reproduced the result with other PD-1 and PD-L1 antibodies, and nivolumab plus ipilimumab (CheckMate 227) offered a chemotherapy-free doublet. For patients with bulky or symptomatic disease pembrolizumab plus platinum doublet (KEYNOTE-189 for non-squamous, KEYNOTE-407 for squamous) gives higher response rates and is the alternative, with no randomised evidence that it prolongs survival over monotherapy in this group. Squamous and non-squamous tumours are treated alike when PD-L1 is high, apart from the chemotherapy partner.
| Setting | Approach | Guideline |
|---|---|---|
| Advanced, first line, PD-L1 50 percent or more | Pembrolizumab alone (KEYNOTE-024, KEYNOTE-042), cemiplimab alone (EMPOWER-Lung 1) or atezolizumab alone; pembrolizumab plus platinum doublet for bulky or symptomatic disease; nivolumab plus ipilimumab as a chemotherapy-free alternative. | not mapped |
| Advanced, first line, PD-L1 1 to 49 percent | Pembrolizumab plus platinum doublet (KEYNOTE-189, KEYNOTE-407); monotherapy is not recommended below 50 percent. | not mapped |
| Advanced, after progression on immunotherapy | Platinum doublet if not yet given; docetaxel with or without ramucirumab; clinical trials of antibody-drug conjugates and bispecifics. | not mapped |
| Duration and stopping | Two years of immunotherapy for patients in response, with retreatment at relapse; management of immune-related adverse events by organ. | not mapped |