Adding durvalumab upfront to chemo ups long-term survival in SCLC

Patients were threefold more likely to survive long term (beyond 3 years) when durvalumab was added to first-line chemotherapy, with or without tremelimumab, compared with those on chemotherapy alone, according to a post hoc analysis of long-term survivors (LTS) with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study.

After a median follow-up of 39.4 months, 16 percent and 14 percent of patients treated with durvalumab + chemotherapy, with or without tremelimumab, respectively, were still alive compared with 5 percent in the chemotherapy alone arm. [ELCC 2022, abstract 141O]

“Three times more patients were estimated to be alive at 3 years when treated with durvalumab plus [chemotherapy vs chemotherapy] alone, with the majority still receiving durvalumab at data cutoff, further establishing durvalumab plus [chemotherapy] as the standard of care for the first-line treatment of ES-SCLC,” the investigators said.  

“To date, biomarkers that predict the efficacy of immune checkpoint blockade have not been well characterized in SCLC,” they noted.

Features of long-term survivors

In a post hoc analysis of LTS presented at the ELCC 2022 Congress, favourable prognostic clinical and molecular characteristics that were associated with long-term survival in these patients were identified.

The analysis included 94 patients with long-term survival (defined as patients still alive at data cutoff date; median follow-up 39.4 months) out of the original 805 patients (intention-to-treat [ITT] population) in CASPIAN —who were randomized 1:1:1 to durvalumab with or without tremelimumab (D±T) plus chemotherapy of etoposide with either cisplatin or carboplatin (EP) or EP alone.

For instance, there were more patients with performance status of 0/1 among LTS than the ITT population in both the D ± T + EP arms, reported lead investigator Dr Niels Reinmuth from Asklepios Lung Clinic in Munich-Gauting, Germany.

“Although LTS had a higher incidence of some favourable prognostic characteristics at baseline than the ITT population, some patients with baseline brain or liver metastases [still] achieved long-term survival,” he pointed out.

“Notably, most LTS completed EP induction,” Reinmuth added. “And, in both the immunotherapy + EP arms, [LTS] had substantially greater overall treatment exposure, as well as achieving higher ORR and longer progression-free survival [PFS], vs ITT.”

At 24 months, PFS rates were consistently higher among LTS than the ITT population (65 percent and 67 percent vs 55 percent for D + EP and D+T+EP vs EP among LTS compared with 11 percent and 12 percent vs 3 percent, respectively, among ITT).

Compared with the ITT population, more LTS had ≥4 cycles of EP across treatment arms. The overall treatment exposure was also longer among LTS than the ITT population in both the combination arms with immunotherapy, with 46 LTS (27 in the D+EP, 19 on D+T+EP) still receiving durvalumab as of cutoff date.  

“Despite longer exposure, LTS did not experience an increase in serious adverse events [AEs] vs the ITT population,” said Reinmuth, who noted that the rates of serious AEs among LTS were similar to that in the ITT population. “The distribution of serious AEs across system organ classes was [also] similar in LTS and the ITT population.”

In terms of molecular features, PD-L1 expression of ≥1 percent (on tumour or immune cells) and the presence of HLA-DQB1*03:01 allele appeared to be associated with longer overall survival in the D + T + EP arm, but not the D + EP arm.    

There was no association between tissue tumour mutation burden and long-term survival in any treatment arms.

“Further investigation is warranted to understand the potential role of these and other biomarkers in SCLC,” said Reinmuth.