A real-world data of Immune checkpoint inhibitors in solid tumors from India

Abstract

Background: Checkpoint inhibitors (Nivolumab and Pembrolizumab) are approved for multiple indications in solid tumors. However access to these therapies is limited in low and middle income countries. Hence we performed an audit to identify accessibility, adverse event rates, compliance, progression free survival and overall survival in solid tumors.

Methods: This was a single center retrospective analysis of prospective data base of patients with non-melanoma solid tumors who were treated with immunotherapy from August 2015 to November 2018. Adverse events during immunotherapy were documented and graded using CTCAE (Common terminology criteria for adverse events), v. 4.02. The response rates to immunotherapy, toxicities and the time to onset and resolution of toxicities were also evaluated as secondary endpoints.

Results: Out of 9610 patients, only 155 patients (1.61%) could receive immunotherapy. The most common malignancies included metastatic non-small cell lung cancer, metastatic renal cell carcinoma, metastatic urothelial carcinoma and relapsed/recurrent head and neck squamous cell carcinoma. Median overall survival in patients who received immunotherapy in non-melanoma solid malignancies was 5.37 months (95% CI, 3.73-9.73). Poor performance status at baseline was the only adverse prognostic factor. The median progression free survival was 2.57 months (95% CI, 1.73-3.83). Immunotherapy was well tolerated with most common side effects being fatigue 14.8% and anorexia 5.8%. The cumulative incidence of immune related adverse events like hepatitis, pneumonitis, colitis and nephritis was less than 10%.

Conclusion: Real-world data in Indian setting confirms the benefit of immunotherapy in patients with advanced non-melanoma solid tumors.

Keywords: CPI; Immunotherapy; India; Nivolumab; Pembrolizumab; checkpoint inhibitors; hepatitis; irAE; pneumonitis.

FIGURE 1

The figure demonstrates the cumulative incidence of adverse events (fatigue, anorexia and adrenal insufficiency) against months after the start of therapy. Competing risk analysis to modify for competing events like death and progression was done and represented in black dotted‐ fatigue, yellow dotted‐ anorexia and grey dotted‐ adrenal insufficiency (RStudio version 3.5.2). The cumulative incidence of these adverse events was below 10% even with consideration of competing events.

FIGURE 2

The figure demonstrates the percentage incidence of immune mediated toxicities with time in patients who were treated with immunotherapy. The cumulative incidence of immune mediated toxicities (magenta dotted‐ colitis) was less than 5 percentage after adjusting for competing risk factors like mortality and progression.

FIGURE 3

Kaplan Meier curve of overall survival in patients on immune check point inhibitors who have received concomitant steroids (blue) and who did not receive cobcomitant steroids. The median OS in the steroid group was 3.90 (1.80–11.4) months versus 5.47 (3.73‐NA) months in patients who did not receive steroids. (HR‐1.95% CI‐0.963‐1.039). There was no stastically significant difference in overall survival in these groups. p = 0.23.

FIGURE 4

Kaplan Meier curve showing overall survival in patients on immune checkpoint inhibitors who received concomitant antibiotics (included patients with IO who received oral /IV antibiotics for various indications for atleast 5 days) versus patient who did not receive concomitant antibiotics. The median OS in the patients who received antibiotics was 3.90 (1.80–11.4) when compared to 9.17 (4.20–12.33) in patients who did not receive antibiotics with a trend to significance with p value‐ 0.053. (HR‐1.023; 95% CI 22121–1.1047).

FIGURE 5

Kaplan Meier curve showing the progression free survival in patients treated with ICI. The 6 month progression free survival was 25.2%.

FIGURE 6

Kaplan Meier curve depicting overall survival in patients treated with ICI. The overall survival at 1 year was 37.5% (95% CI 28.4–46.6).

FIGURE 7

Kaplan Meier curve showing overall survival in patients on immune check point inhibitors comparing the baseline performance status ECOG‐1 was associated with median OS 9.07 (4.43‐NA) months when compared to ECOG 2‐3 which had a median OS of 3.30 (1.80–5.47) months (p = 0.032).

FIGURE 8

Kaplan Meier curve comparing the overall survival in ICI responders (blue) and ICI non responders (red). The median overall survival was not reached for responders of ICI at 30 months. The median overall survival for non responders of ICI was 3.3 (1.97–4.43) months. (p < 0.0001).