Summary
Updated results from the CASPIAN study support the addition of durvalumab to platinum and etoposide as a new standard of care in extensive-stage small cell lung cancer (ES-SCLC). Results were presented at ASCO 2020 Annual Meeting (Abstract 9002).
To explore additional resources offered by Oncology Times and to subscribe, visit https://journals.lww.com/oncology-times/pages/default.aspx
Original Article
Addition of Durvalumab to Platinum + Etoposide in Extensive-Stage SCLC
Oncology Times
By Veronica Hackethal
Updated results from the CASPIAN study support the addition of durvalumab to platinum and etoposide as a new standard of care in extensive-stage small cell lung cancer (ES-SCLC). Results were presented at ASCO 2020 Annual Meeting (Abstract 9002).
“The CASPIAN trial is a first-line trial looking at adding the immunotherapy agent durvalumab to standard platinum-etoposide chemotherapy. With minimal increased side effects, survival was improved significantly on the durvalumab arm,” said senior author Jonathan Wade Goldman, MD, an oncologist at UCLA Medical Center.
“This establishes a meaningful new standard of care that improves outcomes for these patients, who otherwise have had few advances in the last decades,” he added.
The updated results confirm interim results from CASPIAN, which showed significantly improved overall survival for durvalumab plus platinum-etoposide, compared to platinum-etoposide alone (HR 0.75; 95% CI 0.62-0.91; p=0.0032; mOS 12.9 vs. 10.5 months).
Durvalumab is a PD-L1 immune checkpoint inhibitor that was FDA-approved in March 2020 as first-line therapy for patients with ES-SCLC, in combination with etoposide and either carboplatin or cisplatin. One other immunotherapy, atezolizumab, was approved in March 2019 for first-line treatment of ES-SCLC, in combination with carboplatin and etoposide.
The approvals represent the first major improvement in about 30 years for this difficult-to-treat cancer. Before now, standard of care for ES-SCLC has been carboplatin and etoposide, drugs which show a high rate of early benefit but also rapid recurrence that is difficult to treat.
“The excitement about our update was that it confirms that patients are living longer, and that some patients are living substantially longer,” Goldman said. “The survival used to be a little less than a year, and now we’ve extended that. For some people it’s now meaningfully longer, with 22 percent alive at 2 years.”
Still, there’s more work to be done. Right now, only about a fifth of patients have shown meaningfully longer survivals.
“We need to improve the percentage of patients that are doing really well,” Goldman stressed. “We are also hoping to better predict what patients might do well on this treatment, but at this point we haven’t figured out a good biomarker.”
CASPIAN was a randomized, multicenter, open-label phase III trial that compared immunotherapy plus chemotherapy to chemotherapy alone in treatment-naïve patients with ES-SCLC. Participants were randomized to durvalumab plus platinum-etoposide (D + EP, n=268), durvalumab plus tremelimumab plus platinum-etoposide (D + T + EP, n=268), or platinum-etoposide alone (EP, n=269). The primary endpoint was overall survival. Median follow-up was 25.1 months, with 82 percent maturity.
Results showed significantly improved overall survival for D + EP vs EP alone, with a median overall survival of 12.9 months versus 10.5 months, respectively (HR 0.75; 95% CI 0.62-0.91; nominal p=0.0032).
At 2 years, 22.2 percent of patients randomized to D + EP were alive, compared to 14.4 percent of patients with EP alone. Adding tremelimumab failed to show a significant benefit, although overall survival was numerically better with D + T + EP compared to EP alone (HR 0.82; 95% CI 0.68–1.00; p=0.0451, with p≤ 0.0418 required for statistical significance). Median overall survival with D + T + EP was 10.4 months, with 23.4 percent of patients still alive at 2 years.
Lack of benefit was thought to be related to side effects that limited treatment delivery in the D + T + EP arm.
Among secondary endpoints, progression-free survival (PFS) and objective response rate (ORR) remained improved with D + EP compared to EP. ORR and median PFS were similar for D + T+ EP and EP. In general, adverse event rates were similar for D+EP and EP, but higher in the D+T+EP arm.
| D + EP (n=268) | D + T + EP (n=268) | EP (n=269) | |
|---|---|---|---|
| Median OS | 12.9 months | 10.4 months | 10.5 months |
| Percentage alive at 2 years | 22.2% | 23.4% | 14.4% |
| All-cause AEs grade 3/4 | 62.3% | 70.3% | 62.8% |
| AEs leading to treatment discontinuation | 10.2% | 21.4% | 9.4% |
| AEs leading to death | 4.9% | 10.2% | 5.6% |
Veronica Hackethal is a contributing writer.