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IMFINZI (durvalumab) - Cancer bronchique à petites cellules à un stade étendu (CBPC-SE)

Opinions on drugs - Posted on Mar 11 2021

Reason for request

New indication

Key points

Favourable opinion for reimbursement in combination with etoposide and either carboplatin or cisplatin for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC).

What therapeutic improvement?

Therapeutic improvement compared to carboplatin/cisplatin + etoposide chemotherapy.

Role in the care pathway?

The treatment of extensive-stage small cell lung cancer (ES-SCLC) is based on a combination of chemotherapies, with several protocols having demonstrated similar efficacy.

The first-line treatment is the cisplatin/carboplatin + etoposide protocol for 4 to 6 cycles. For elderly, frail patients (ECOG ≥ 2) or in whom the use of cisplatin is contraindicated, the use of carboplatin is recommended.

The latest American NCCN (2020) and AURA (2020) guidelines recommend the use of immunotherapy, atezolizumab (TECENTRIQ) or durvalumab (IMFINZI), in combination with platinum salt-based induction chemotherapy then maintenance therapy.

Other protocols may also be used, particularly in the event of a contraindication to etoposide, such as combinations with irinotecan.

Complementary radiotherapy of the chest for PS (0-1) patients, demonstrating a significant response following chemotherapy and with a limited extrathoracic tumour mass may be discussed (stage IV).

Role of the medicinal product in the care pathway

IMFINZI (durvalumab), anti-PD-L1 immunotherapy, used in combination with carboplatin or cisplatin + etoposide chemotherapy, then alone as a maintenance therapy, is a first-line treatment option in adult patients with extensive-stage SCLC. Its efficacy in terms of overall survival has been demonstrated, in combination with etoposide and with either carboplatin or cisplatin as the platinum salt.

The Committee nevertheless highlights that:

  • a subpopulation of “good responder” patients appears to benefit from long-term treatment, without it being possible to identify these patients,
  • no data are available in patients with an ECOG performance score > 1, and
  • data is limited in patients with brain metastases.

Clinical Benefit

Substantial

The Committee deems that the clinical benefit of IMFINZI (durvalumab) is substantial in the new MA indication.


Clinical Added Value

minor

Considering:

  • demonstration of the superiority of durvalumab combined with carboplatin or cisplatin + etoposide chemotherapy compared to chemotherapy alone, in a randomised, open-label study, in terms overall survival (OS, primary endpoint),
  • the effect size, deemed to be modest but clinically relevant in view of the disease with an improvement in OS of 2.7 months; HR = 0.73; CI98,22% [0.56; 0.95]; p=0.0047),
  • the absence of robust data relative to progression-free survival considered to be exploratory given the interruption of the hierarchical analysis sequence,

and despite:

  • the exploratory nature of the quality of life data,
  • the acceptable safety profile of the durvalumab + carboplatin or cisplatin + etoposide combination compared to chemotherapy alone with a comparable frequency of grade ≥ 3 AEs (62.3% vs. 62.8%) and SAEs (32.1% vs. 36.5%) but marked by immune-mediated AEs (20% in the durvalumab + carboplatin/etoposide group),
  • uncertainty concerning the effect of durvalumab given the difficulty in differentiating between the proportion attributable to the induction therapy in combination with chemotherapy and that attributable to maintenance therapy with durvalumab alone, and
  • the impossibility of identifying “good responder” patients who appear to benefit from long-term treatment,

the Committee considers that IMFINZI (durvalumab) in combination with carboplatin and etoposide, like TECENTRIQ (atezolizumab), provides a minor clinical added value (CAV IV) compared to chemotherapy alone, in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC).


 

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