Immunotherapy Improves Survival by 10% Compared to Chemo

Megan Brooks

August 26, 2022

Data from two separate meta-analyses have confirmed benefits for immunotherapy with immune checkpoint inhibitors (ICIs). One of the reviews used an advanced statistical method to show that ICIs improved survival by about 10% when compared with chemotherapy, while the other showed that ICIs do not diminish quality of life in patients with cancer.

The new survival data come from a systematic review and meta-analysis of 13 clinical trials across three cancer types: non-small-cell lung cancer, urothelial carcinoma, and melanoma.

The study was published online August 17 in JAMA Network Open.

Researchers used an advanced statistical method — Cox proportional hazards–Taylor expansion adjustment for long-term survival data (Cox-TEL) — to overcome the issues of long tails and early crossover seen in trials with these agents. These features have long raised questions about the suitability of the usual statistical method used: traditional Cox proportional hazards regression for ICI survival analysis.

"The time has come to address this issue and provide a suitable statistical method to ensure better data interpretation and appropriate clinical decision-making for ICI therapy," the authors, led by Emily Pei-Ying Lin, MD, PhD, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, comment.  

The team estimated overall survival benefits of ICI therapy (vs chemotherapy) before and after Cox-TEL adjustment.

They transformed Cox proportional hazard ratios (HRs) to Cox-TEL HRs for short-term survivors (ST-HR) and determined the difference in proportions for patients with long-term survival (LT-DP) by Cox-TEL.

In all three cancer types, the ST-HR for overall survival was consistently larger than the Cox HR, suggesting the contribution of the long-term survivor population to the estimation of Cox HR.

The pooled findings for overall survival were 0.75 (95% CI, 0.70 - 0.81) for HR, 0.86 (95% CI, 0.81 - 0.92) for ST-HR, and 0.08 (95% CI, 0.06 - 0.10) for LT-DP.

This COX-TEL adjustment method used to examine long-term survival probability consistently noted an increase of roughly 10% over chemotherapy in patients with long-term survival who were receiving ICI therapy, the researchers report.

The findings, they say, show that Cox proportional hazard ratios "may not provide a full picture of survival outcomes when the risk reduction from the treatment is not constant; Cox-TEL correction for appropriate data interpretation may be useful."

No Decline in Quality of Life

The other study, also published in JAMA Network Open, found that ICI therapy has a favorable impact on patient quality of life and can be combined with other anticancer drugs without worsening quality of life.

These findings are also based on a systematic review and meta-analysis, this time including 34 randomized clinical trials involving 18,709 patients with solid tumors.

"Our results clearly show that differences in patient-reported outcomes (PROs) over time favor immunotherapy in trials testing ICI monotherapy," report Laura Pala, MD, European Institute of Oncology, Milan, Italy, and colleagues.

They note, however, that in trials testing ICI-containing combinations, the degree of PRO improvement in favor of immunotherapy at 12 or 24 weeks was "limited and under the clinically relevant cutoff."

This result, they say, does not allow for the conclusion of better health-related quality of life in patients treated with an ICI combination. However, it does support the conclusion that none of the multidrug combinations worsened patient quality of life compared with control groups.

"This finding is noteworthy considering that in some randomized clinical trials, patients received up to three different classes of drugs," the authors write.

Neither study had commercial funding. The authors of both studies reported no relevant financial relationships.

Lin E, et al JAMA Netw Open. Published online August 17, 2022. Full text

Pala L, et al. JAMA Netw Open. Published online August 16, 2022. Full text

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