Leading Researchers Dissect PD-1/PD-L1 Evidence in NSCLC

Christina Loguidice
Published: Thursday, Sep 15, 2016
“The combination produces impressive response rates,” said Govindan, noting 1-year survival data >70% and median PFS >8 months. “The results may not be as impressive as what we see in melanoma, but certainly give hope that the blocking of CTLA-4 and the PD-1/PD-L1 axis is an important one.”

Another similar combination showing promise in the refractory setting is durvalumab with tremelimumab, a PD-L1/CTLA-4 inhibitor combination.5 This combination showed clinical activity in patients with and without PD-L1–positive tumors.

Objective responses were achieved by 6 of 26 patients (23%) in the cohort that received tremelimumab at 1 mg/kg and durvalumab at 10-20 mg/kg. The responders consisted of 2 of 9 patients (22%) with PD-L1–positive (≥25% stain) tumors and 4 of 14 patients (29%) with PD-L1-negative (<25% stain) tumors, including those with no PD-L1 staining (4 of 10 patients [40%]).5 Toxicity was manageable.

“I think it’s a really interesting strategy, one that may be beneficial to more patients than some of the single-agent strategies,” said Goldberg. “The toxicity probably is more, [which is] true for other combinations of CTLA-4 and PD-1 or PD-L1, but, again, with vigilance and monitoring and aggressively treating patients with toxicity, typically it’s manageable,” she said. Kris noted that a trial will be starting at his institution assessing this combination in the neoadjuvant setting.

Because immunotherapies as single agents are not yet working in the majority of patients with NSCLC, many of the panelists’ concluding remarks encouraged enrollment into clinical trials.

“We should do everything we can to get our patients on appropriate clinical trials, and then follow the data very carefully and try to move along with science,” said Govindan.

Oncologists were also urged to think about curative strategies, which might include novel drug combinations. “We really got to look to curative strategies. It’s nice to bend the curve, but you want to raise the curve. And I urge everybody to think about [that] in every individual patient: is there a strategy that can lead to cure? That’s really what you want to do and that’s what the patient wants,” said Kris.

References

  1. American Lung Association. Lung Cancer Fact Sheet. http://goo.gl/EvuNfo. Updated 2015. Accessed August 26, 2016.
  2. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584-594.
  3. Goldberg SB, Gettinger SN, Mahajan A, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol. 2016;17(7):976-983.
  4. Hellmann MD, Gettinger SN, Goldman JW, et al. CheckMate 012: safety and efficacy of first-line (1L) nivolumab (nivo; N) and ipilimumab (ipi; I) in advanced (adv) NSCLC. J Clin Oncol. 2016;34(suppl;abstr 3001).
  5. Antonia S, Goldberg SB, Balmanoukian A, et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016;17(3):299-308.



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