Serplulimab (1) – Hetronifly®

• Clinical trials
  • The ASTRUM-005 and IMpower133 trials are completed, double-blind, phase III RCTs that enrolled previously untreated patients with advanced small-cell lung cancer (ES-SCLC).
  • The pivotal trial for serplulimab in this therapeutic indication is the Phase III RCT ASTRUM-005, in which serplulimab in combination with carboplatin and etoposide was compared with carboplatin in combination with etoposide.

Adults with advanced-stage small cell lung cancer (ES-SCLC); first-line treatment

• Overall, the G-BA classifies the extent of the additional benefit of serplulimab in combination with carboplatin and etoposide for the treatment of advanced-stage small cell lung cancer (ES-SCLC) as non-quantifiable, because the scientific evidence does not permit quantification.
• Overall, the data are subject to significant uncertainties, which is why the certainty of the evidence for the established additional benefit is classified as a ‘hint’.
• mortality
  • For the endpoint ‘overall survival’, no difference was observed for comparable observation periods between the ASTRUM-005 (2nd data cut-off date of 13 June 2022) and the overall cohort of the IMpower133 study (2nd data cut-off date of the global cohort on 24 January 2019 and 3rd data cut-off for the China cohort on 31 July 2019), no statistically significant difference was observed between serplulimab and atezolizumab in the adjusted indirect comparison.
• Morbidity – General health status as measured by the EQ-5D-VAS
  • No usable data are available for the endpoint ‘General health status as measured by the EQ-5D-VAS’ for the adjusted indirect comparison.
• Health-related quality of life – EORTC QLQ-C30
  • No usable data from the EORTC QLQ-C30 survey are available for this endpoint in the adjusted indirect comparison.
• Side effects – Serious adverse events (SAE)
  • Data are available for serious adverse events (SAEs) and severe adverse events for comparable observation periods between the ASTRUM-005 (2nd data cut-off date of 13 June 2022) and the overall cohort of the IMpower133 study (1st data cut-off date of the global cohort on 24 April 2018 and 3rd data cut-off for the China cohort on 31 July 2019).
  • For the SAE, no significant difference was observed in the adjusted indirect comparison between serplulimab and atezolizumab.
• Side effects – severe adverse events (CTCAE grade 3 or 4)
  • For severe adverse events, the pharmaceutical manufacturer has subsequently submitted data categorised as CTCAE grade 3 or 4 to enable a comparison between the two studies.
  • Given the difference in treatment duration between the study arms in the ASTRUM-005 trial, it can be assumed that the observation period for the safety endpoints, which is linked to the treatment duration, also differed.
  • Furthermore, in the IMpower133 study, ‘severe AEs’ were recorded up to a maximum of 30 days after the end of treatment, whereas in the ASTRUM-005 study, they were recorded up to a maximum of day 90.
  • The effect estimator submitted subsequently for the adjusted indirect comparison was presented as a relative risk and is therefore not usable due to the differing observation periods.
• Side effects – discontinuation due to adverse events (AEs)
  • Data are available for this endpoint for comparable observation periods between the ASTRUM-005 study (2nd data cut-off on 13 June 2022) and the global IMpower133 cohort (1st data cut-off on 24 April 2018) .
  • The event rates for this endpoint were comparable in the intervention arms of the two studies; however, significantly fewer events occurred in the placebo arm of the IMpower133 study than in the ASTRUM-005 study.
  • This introduces additional uncertainty into the interpretation of the result from the adjusted indirect comparison.
  • Overall, the statistically significant effect from the adjusted indirect comparison is deemed insufficiently robust to allow conclusions to be drawn.
• Conclusion
  • This assessment is based on the adjusted indirect comparison according to Bucher of the Phase III studies ASTRUM-005 (serplulimab + chemotherapy vs. chemotherapy) and IMpower133 (atezolizumab + chemotherapy vs. chemotherapy), in which serplulimab was compared with atezolizumab via the bridge comparator of chemotherapy.
  • Results on mortality and side effects are available from the adjusted indirect comparison.
  • For the endpoint of overall survival, there is no statistically significant difference between serplulimab and atezolizumab.
  • With regard to side effects, no advantages or disadvantages can be identified on the basis of limited data, some of which involves effect estimators from the adjusted indirect comparison that are of limited interpretability.
• Overall assessment
  • In its overall assessment, the G-BA classifies the extent of the additional benefit of serplulimab in combination with carboplatin and etoposide for the treatment of advanced-stage small cell lung cancer (ES-SCLC) as non-quantifiable, because the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.