Clinical trial shows combination immunotherapy treatment effective before lung cancer surgery

Medical Xpress / University of Texas M. D. Anderson Cancer Center / Cancer Discovery ^ | Sept. 14, 2023 | Tina Cascone et al

[ConservativeMind]

Combination immunotherapy with the anti-PD-L1 monoclonal antibody durvalumab and other novel agents outperforms durvalumab alone in the neoadjuvant (pre-surgical) setting for early-stage non-small-cell lung cancer (NSCLC), according to researchers.

The multicenter, randomized Phase II NeoCOAST clinical trial evaluated neoadjuvant durvalumab alone and in combination with each of the following novel immunotherapies: the anti-CD73 monoclonal antibody oleclumab, the anti-NKG2A monoclonal antibody monalizumab, and the anti-STAT3 antisense oligonucleotide danvatirsen.

The NeoCOAST study enrolled 84 patients with untreated, resectable (>2cm), stage I-IIIA NSCLC. Eighty-three patients received one 28-day cycle of neoadjuvant durvalumab alone or combined with another therapy.

The investigators assessed pathological complete response (pCR), or complete disappearance of viable tumor cells, as a secondary endpoint.

All combinations had numerically higher rates of MPR and pCR than monotherapy.

For the patients who received durvalumab monotherapy, MPR occurred in 11.1% and pCR in 3.7%, which is comparable to results from other monotherapy studies.

MPR rates for combination therapy ranged from 19% (oleclumab) to 31.3% (danvatirsen), and pCR rates ranged from 9.5% (with oleclumab) to 12.5% (with danvatirsen). For combination therapy with monalizumab, MPR was 30% and pCR was 10%.

MPR was associated with baseline tumor PD-L1 expression of ≥1% in the oleclumab and monalizumab combination arms. In the oleclumab (anti-CD73) combination arm, high baseline CD73 expression was associated with pathological tumor regression, and treatment decreased CD73 expression on tumor cells.

The oleclumab combination also was associated with greater natural killer (NK) and CD8 T cell density in the tumor center on treatment compared with baseline, suggesting an increased infiltration of effector cells in the tumor microenvironment.

The number of patients with no detected circulating tumor DNA (ctDNA) increased progressively from pre-to post-treatment and post-surgery follow up. Notably, surgery was the most effective intervention to result in clearance of ctDNA.

[ConservativeMind]

Major pathological response = (MPR)

Safety was similar to other studies.

The extra therapy greatly increased pathological complete response rates from 3.7% to as high as 12.5% with danvatirsen. Pathological complete response is a complete lack of any remaining cancer being found so it’s basically being cured. MPR went from 11.1% to 31.3%, when danvatirsen was added.

Surgery was the most effective intervention.

[ConservativeMind]

The “Take Charge Of Your Health” Ping List
This high volume ping list is for health articles and studies which describe something you or your doctor, when informed, may be able to immediately implement for your benefit.

Email me to get on either the “Common/Top Issues” (20 - 25% fewer pings) or “Everything” list.

[Husker24]

It’s always non small cell, do they even try new treatments on small cell?

[ConservativeMind]

I’ve posted a few, but they seem less common.