CPNPC avancé : amélioration de la survie à cinq ans avec le pembrolizumab

L'inhibiteur PD-1 pembrolizumab améliore significativement le taux de survie à 5 ans des patients atteints de cancer du poumon non à petites cellules (CPNPC). Une efficacité particulièrement remarquable chez les patients dont l'expression PD-L1 est élevée (article en anglais).

Longer survival due to higher PD-L1 expression levels

The PD-1 inhibitor pembrolizumab (Keytruda) significantly improves the 5-year survival rates of patients with non-small cell lung cancer (NSCLC). The effect was particularly good in patients with high PD-L1 expression.

These findings were obtained by a long-term evaluation of the Phase I study KEYNOTE 001, which was started in 2011 and presented as a poster by Edward B. Garon; David Geffen School of Medicine, Los Angeles, California, USA at the annual meeting of the American Society for Clinical Oncology (ASCO) on June 2, 2019. After 5 years, 23.2% of the patients not pretreated with chemotherapy and 15.5% of the pretreated patients were still alive.

The PD1 inhibitor pembrolizumab was initially approved in 2014 for the treatment of melanoma, but can now be used in a variety of tumors, including NSCLC in various therapy lines and tumor stages. The KEYNOTE-001 Phase 1 trial was the first clinical trial to use pembrolizumab in patients with multiple tumors. In the study, 555 patients with advanced NSCLC received pembrolizumab 2mg mg/kg body weight every 3 weeks or 10mg/kg body weight every 2 to 3 weeks. Today, pembrolizumab is administered as a single dose of 200mg every 3 weeks, regardless of body weight. Of the 550 participants, 449 were pretreated, 101 received the PD-1 inhibitor as first-line therapy.

Follow-up over more than 60 months

Patients were monitored for a median of 60.6 months. After this time, 100 participants (18%) were still alive, 23.3% who had not received pre-treatment and 15.5% who had received pre-treatment. Higher PD-L1 levels increased the chance of longer survival. After 5 years, 29.6% of patients still lived without pretreatment with PD-L1 expression of at least 50% compared to 15.7% with PD-L1 expression below 50%. The corresponding figures for the pretreated patients: 12.6% with high PD-L1 expression, 3.5% with lower PD-L1 expression.

The response rate of pretreated patients was 42% and the median response time was 16.8 months. The response rate of untreated patients was 23% with a duration of 38.9 months.

A total of 60 patients had received pembrolizumab for at least 2 years. Of these, 46 were still alive at the time of the current evaluation.

Immunotoxic effects were observed in 17% of patients, with hypothyroidism most common with an incidence of 8 to 9%. Pneumonitis was registered in about 4% of the cases, half from grade 3 to 5.

"The fact that we have patients in this study who are still alive even after 7 years is quite remarkable," Garon said at an ASCO press conference. "We also note that most patients who are doing well after 2 years of pembrolizumab are also achieving the 5-year survival mark - and even longer."

ASCO expert David L. Graham, Levine Cancer Institute, Charlotte, North Carolina, USA, commented at the press conference: "These data correspond to what we see with immunotherapy in other cancers: There is a patient population that survives 5 and more years. It is remarkable that we are no longer able to calculate survival times in months for more and more patients, but in years". Previously, only about 5% or less of patients with metastatic NSCLC survived 5 years. However, Graham added, "We still have a long way to go to improve outcomes for all patients with advanced lung cancer."

Garon EB, et al. Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001. 2019 ASCO Annual Meeting, Chicago, May 31 to June 4, 2019, Abstract LBA9015.http://abstracts.asco.org/239/AbstView_239_255115.html